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Patterns of Regional Cerebral Blood Flow as a Function of Age Throughout the LifespanRead More
Amen, Daniel G.a; Egan, Sachitb; Meysami, Somayehc; Raji, Cyrus A.d; George, Noblee


Background: Understanding the influence of aging on the brain remains a challenge in determining its role as a risk factor for Alzheimer’s disease. Objective:To identify patterns of aging in a large neuroimaging cohort.

Method: A large psychiatric cohort of 31,227 individuals received brain SPECT at rest and during a concentration task for a total of 62,454 scans. ANOVA was done to identify the mean age trends over the course of the age range in this group, 0–105 years. A regression model in which brain SPECT regions of interest was used to predict chronological age (CA) was then utilized to derive brain estimated age (BEA). The difference between CA and BEA was calculated to determine increased brain aging in common disorders in our sample such as depression, dementia, substance use, and anxiety.

Results: Throughout the lifespan, variations in perfusion were observed in childhood, adolescence, and late life. Increased brain aging was seen in alcohol use, cannabis use, anxiety, bipolar, schizophrenia, attention-deficit/hyperactivity disorder, and in men.

Conclusion: Brain SPECT can predict chronological age and this feature varies as a function of common psychiatric disorders.

Deficits in Regional Cerebral Blood flow on Brain SPECT Predict Treatment Resistant DepressionRead More
Amen DG, Taylor DV, Meysami S, Raji CA


Background: Depression remains an important risk factor for Alzheimer’s dementia, yet few neuroimaging biomarkers are available to identify treatment response in depression. Objective: To analyze and compare functional perfusion neuroimaging in persons with treatment resistant depression (TRD) compared to those experiencing full remission.

Method: A total of 951 subjects from a community psychiatry cohort were scanned with perfusion single photon emission computed tomography (SPECT) of the brain in both resting and task related settings. Of these, 78% experienced either full remission (n = 506) or partial remission (n = 237) and 11% (n = 103) were non-responsive and 11% (n=105). Severity of depression symptoms were used to define these groups with changes in the Beck Depression Inventory (BDI) prior to and following treatment. Voxel based analyses of brain SPECT images from full remission compared to the worsening group was conducted with the statistical parametric mapping software, version 8 (SPM 8). Multiple comparisons were accounted for with a false discovery rate (FDR, p < .001).

Results: Persons with depression that worsened following treatment had reduced cerebral perfusion compared to full remission in the multiple regions including the bilateral frontal lobes, right hippocampus, left precuneus, and cerebellar vermis. Such differences were observed on both resting and concentration SPECT scans.

Conclusion: Our findings identify imaging based biomarkers in persons with depression related to treatment response. These findings have implications in understanding both depression to prognosis and its role as a risk factor for dementia.


Gender-Based Cerebral Perfusion Differences in 46,034 Functional Neuroimaging ScansRead More
Amen, Daniel G.; Trujillo, Manuel; Keator, David; Taylor, Derek V.; Willeumier, Kristen; Meysami, Somayeh; and Raji, Cyrus A.


Background: Studies have reported that females have widespread increases in regional cerebral blood flow, but the studies were relatively small and inconsistent. Objective: Here we analyzed a healthy and very large psychiatric population to determine the effect of gender, using single photon emission computed tomography (SPECT).

Method: Whole brain and region of interest (ROI) gender differences were analyzed in a total of 46,034 SPECT scans at baseline and concentration. The sample included 119 healthy subjects and 26,683 patients; a subset of 11,587 patients had complete diagnostic information. A total of 128 regions were analyzed according to the AAL Atlas, using ROI Extract and SPSS statistical software programs, controlling for age, diagnoses, and correcting for multiple comparisons.

Results: Compared to males, healthy females showed significant whole brain (p < 0.01) and ROI increases in 65 baseline and 48 concentration regions (p < 0.01 corrected). Healthy males showed non-significant increases in 9 and 22 regions, respectively. In the clinical group, there were widespread significant increases in females, especially in the prefrontal and limbic regions, and specific increases in males in the inferior occipital lobes, inferior temporal lobes, and lobule 7 and Crus 2 of the cerebellum. These findings were replicated in the subset of 11,587 patients with the effect of diagnoses removed.

Conclusion: Our results demonstrated significant gender differences in a healthy and clinical population. Understanding these differences is crucial in evaluating functional neuroimaging and may be useful in understanding the epidemiological gender differences among psychiatric disorders.

Discriminative Properties of Hippocampal Hypoperfusion in Marijuana Users Compared to Healthy Controls: Implications for Marijuana Administration in Alzheimer’s Dementia.Read More
Amen DG, Darmal B, Raji CA, Bao W, Jorandby L, Meysami S, Raghavendra CS.


Background: Few studies have evaluated the impact of marijuana use on regional cerebral blood flow.

Objective: To determine whether perfusion in specific brain regions on functional neuroimaging, including those affected by Alzheimer’s disease pathology, are abnormal in marijuana users compared to controls.

Method: Persons with a diagnosis of cannabis use disorder by DSM-IV and DSM-V criteria (n = 982) were compared to controls (n = 92) with perfusion neuroimaging with SPECT at rest and at a concentration task. Perfusion estimates were quantified using a standard atlas. Cerebral perfusion differences were calculated using one-way ANOVA. Diagnostic separation was determined with discriminant analysis of all subjects. Feature selection with a minimum redundancy maximum relevancy (mRMR) identified predictive regions in a subset of marijuana users (n = 436) with reduced psychiatric co-morbidities.

Results: Marijuana users showed lower cerebral perfusion on average (p < 0.05). Discriminant analysis distinguished marijuana users from controls with correct classification of 96% and leave one out cross-validation of 92%. With concentration SPECT regions, there was correct classification of 95% with a leave-one-out cross validation of 90%. AUC analysis for concentration SPECT regions showed 95% accuracy, 90% sensitivity, and 83% specificity. The mRMR analysis showed right hippocampal hypoperfusion on concentration SPECT imaging was the most predictive in separating marijuana subjects from controls.

Conclusion: Multiple brain regions show low perfusion on SPECT in marijuana users. The most predictive region distinguishing marijuana users from healthy controls, the hippocampus, is a key target of Alzheimer’s disease pathology. This study raises the possibility of deleterious brain effects of marijuana use.

Classification of Depression, Cognitive Disorders, and Co-Morbid Depression and Cognitive Disorders with Perfusion SPECT Neuroimaging.Read More
Amen DG, Krishnamani P, Meysami S, Newberg A, Raji CA.


Background: Depression and cognitive disorders (CDs) are two common co-morbid afflictions that commonly present with overlapping symptoms.

Objective: To evaluate if perfusion neuroimaging with brain SPECT can distinguish persons with depression from those with CDs or both conditions.

Method: Inclusion criteria were DSM-IV defined depression or CDs (Alzheimer’s disease, vascular dementia, dementia not otherwise specified, and amnestic disorders not otherwise specified) including persons with both (total n = 4,541; 847 CDs, 3,269 depression, 425 with both). Perfusion differences between the groups were calculated using two-sampled t-tests corrected for multiple comparisons. Diagnostic separation was determined with discriminant analysis. Feature selection revealed predictive regions in delineating depression from CDs and comorbid cases.

Results: Persons with CDs had lower cerebral perfusion compared to depression. In co-morbid persons, cerebral hypoperfusion was additive, with regions showing lower regional cerebral blood flow compared to either diagnosis alone. Both baseline and concentration SPECT regions yielded correct classification of 86% and leave one out cross-validation of 83%. AUC analysis for SPECT regions showed 86% accuracy, 80% sensitivity and 75% specificity. Discriminant analysis separated depression and CDs from comorbid cases with correct classification of 90.8% and cross validated accuracy of 88.6%. Area under the curve was 83% with sensitivity of 80% and specificity of 70%. Feature selection identified the most predictive regions in left hippocampus, right insula, cerebellar, and frontal lobe regions.

Conclusion: Quantitative perfusion SPECT neuroimaging distinguishes depression from dementia and those with both co-morbidities. Perfusion brain SPECT can be utilized clinically to delineate between these two disorders.

Quantitative Erythrocyte Omega-3 EPA Plus DHA Levels are Related to Higher Regional Cerebral Blood Flow on Brain SPECT.Read More
Amen DG, Harris WS, Kidd PM, Meysami S, Raji CA.


Background: The interrelationships between omega-3 fatty acids status, brain perfusion, and cognition are not well understood.

Objective: To evaluate if SPECT brain imaging of cerebral perfusion and cognition varies as a function of omega-3 fatty acid levels.

Method: A random sample of 166 study participants was drawn from a psychiatric referral clinical for which erythrocyte quantification of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (the Omega-3 Index) was available. Quantitative brain SPECT was done on 128 regions based on a standard anatomical Atlas. Persons with erythrocyte EPA+DHA concentrations were dichotomized based on membership in top 50th percentile versus bottom 50th percentile categories. Two-sample t-tests were done to identify statistically significant differences in perfusion between the percentile groups. Partial correlations were modeled between EPA+DHA concentration and SPECT regions. Neurocognitive status was assessed using computerized testing (WebNeuro) and was separately correlated to cerebral perfusion on brain SPECT imaging and omega-3 EPA+DHA levels.

Results: Partial correlation analyses showed statistically significant relationships between higher omega-3 levels and cerebral perfusion were in the right parahippocampal gyrus (r = 0.20, p = 0.03), right precuneus (r = 0.20, p = 0.03), and vermis subregion 6 (p = 0.21, p = 0.03). Omega-3 Index levels separately correlated to the feeling subsection of the WebNeuro (r = 0.25, p = 0.01).

Conclusion: Quantitative omega-3 EPA+DHA erythrocyte concentrations are independently correlated with brain perfusion on SPECT imaging and neurocognitive tests. These results have implications for the role of omega-3 fatty acids toward contributing to cognitive reserve.


Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population.Read More
Amen DG, Willeumier K, Omalu B, Newberg A, Raghavendra C, Raji CA.


Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public.

Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls.

Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models.

Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification.

Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.


Amen DG, Raji CA, Willeumier K, Taylor D, Tarzwell R, Newberg A, Henderson TA (2015)
Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets
Read More
PLOS One, Jul 1;10(7):e0129659. doi: 10.1371/journal.pone.0129659.


Background: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.

Method: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 with TBI (n=7,505), PTSD (n=1,077) or both (n=1,017) compared to n=11,147 without either. ROIs and visual readings (VRs) were analyzed using a binary logistic regression model with predicted probabilities inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. One-way ANOVA identified the most diagnostically significant regions of increased perfusion in PTSD compared to TBI. Analysis included a 10-fold cross validation of the protocol in the larger community sample (Group 2).

Results: For Group 1, baseline and on-task ROIs and VRs showed a high level of accuracy in differentiating PTSD, TBI and PTSD+TBI conditions. This carefully matched group separated with 100% sensitivity, specificity and accuracy for the ROI analysis and at 89% or above for VRs. Group 2 had lower sensitivity, specificity and accuracy, but still in a clinically relevant range. Compared to subjects with TBI, PTSD showed increases in the limbic regions, cingulum, basal ganglia, insula, thalamus, prefrontal cortex and temporal lobes.

Conclusion(s): This study demonstrates the ability to separate PTSD and TBI from healthy controls, from each other, and detect their co-occurrence, even in highly comorbid samples, using SPECT. This modality may offer a clinical option for aiding diagnosis and treatment of these conditions.

Raji CA, Willeumier K, Taylor D, Tarzwell R, Newberg A, Henderson TA, Amen DG (2015)
Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population
Read More
Brain Imaging and Behavior; Apr 23.


Background: PTSD and TBI are two common conditions in veteran populations that can be difficult to distinguish clinically. The default mode network (DMN) is abnormal in a multitude of neurological and psychiatric disorders.

Objective: We hypothesize that brain perfusion SPECT can be applied to diagnostically separate PTSD from TBI reliably in a veteran cohort using DMN regions.

Method: A group of 196 veterans (36 with PTSD, 115 with TBI, 45 with PTSD/TBI) were selected from a large multi-site population cohort of individuals with psychiatric disease. Inclusion criteria were peacetime or wartime veterans regardless of branch of service and included those for whom the traumatic brain injury was not service related. SPECT imaging was performed on this group both at rest and during a concentration task. These measures, as well as the baseline-concentration difference, were then inputted from DMN regions into separate binary logistic regression models controlling for age, gender, race, clinic site, co-morbid psychiatric diseases, TBI severity, whether or not the TBI was service related, and branch of armed service. Predicted probabilities were then inputted into a receiver operating characteristic analysis to compute sensitivity, specificity, and accuracy.

Results: Compared to PSTD, persons with TBI were older, male, and had higher rates of bipolar and major depressive disorder (p < 0.05). Baseline quantitative regions with SPECT separated PTSD from TBI in the veterans with 92 % sensitivity, 85 % specificity, and 94 % accuracy. With concentration scans, there was 85 % sensitivity, 83 % specificity and 89 % accuracy. Baseline-concentration (the difference metric between the two scans) scans were 85 % sensitivity, 80 % specificity, and 87 % accuracy. In separating TBI from PTSD/TBI visual readings of baseline scans had 85 % sensitivity, 81 % specificity, and 83 % accuracy. Concentration scans had 80 % sensitivity, 65 % specificity, and 79 % accuracy. Baseline-concentration scans had 82 % sensitivity, 69 % specificity, and 81 % accuracy. For separating PTSD from PTSD/TBI baseline scans had 87 % sensitivity, 83 % specificity, and 92 % accuracy. Concentration scans had 91 % sensitivity, 76 % specificity, and 88 % accuracy. Baseline-concentration scans had 84 % sensitivity, 64 % specificity, and 85 % accuracy.

Conclusion(s): This study demonstrates the ability to separate PTSD and TBI from each other in a veteran population using functional neuroimaging


Messerly J, Link J, Hayhurst H, Roberts C, Amen D, Willeumier K, Taylor D, Golden C (2014)
A Preliminary Investigation of SPECT Differences between Individuals with Varying Levels of Anxiety
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Archives of Clinical Neuropsychology, 29(6): 579


Objective: The purpose of this study was to conduct an investigation of brain areas related to anxiety using SPECT scans.

Method: Participants were administered a SPECT scan as part of a general evaluation for a wide variety of psychiatric disorders ranging from ADHD to schizophrenia and brain disorders. They were grouped based on their responses to symptom questionnaires targeting anxiety symptoms specifically. Three groups were formed and were based on quartiles: lower anxiety (1, 719), moderate anxiety (5, 239), and high anxiety (2, 663).

Results: A MANOVA was significant at the .05 level, Wilks λ = .954; F(116, 223) = 1.934, p = .001. Individuals in the moderate and high groups had significantly greater blood flow than the low group in the left cerebellum and caudate. Individuals in the high group had significantly greater blood flow than the low group in the right cerebellum, and left and right olfactory bulbs. Individuals in the low group had greater blood flow than the high group in the left and right occipital lobe.

Conclusion(s): The results demonstrated that various areas of the brain, based on average amount of blood flow, differ based on varying levels of self-reported anxiety symptoms. No significant pattern of results emerged, which could demonstrate that blood flow in individuals with high levels of anxiety more global changes rather than specific to one area of the brain. Future research should investigate more specifically the areas of the brain that differ between individuals to determine possible mechanisms by which they influence each other.

Driskell L, Link J, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Exploratory Analysis of Differentiating Mania Symptomology Severity
Read More
Archives of Clinical Neuropsychology, 29(6): 578


Objective: To assess which brain areas, as measured by SPECT, were related to severity of mania symptomology.

Method: Using a symptom checklist, participants (57.3% male, mean age = 40.93 years, SD = 15.71) were determined based on their scores on a factor measuring Mania symptomatology. Quartiles based on upper 25th (n = 5314), middle 50th (n = 1043), and lower 75th percentiles (n = 2509) were computed to examine the between group differences in blood flow for various regions of the brain.

Results: A MANOVA was conducted at the .05 level, providing significant differences between the upper and lower quartiles of the clients with mania symptoms, Wilks’ λ = .965; F(240, 17, 488) = 1.294, p = .002. Subjects in the upper quartile yielded significantly lower blood flow relative to the lower quartile in the following areas: amygdala, calcarine, caudate nucleus, cerebellum, cingulum, Heschl’s gyrus, hippocampus, insula, globus pallidus, putamen, inferior, mid and superior temporal lobe, and thalamus.

Conclusion(s): The purpose of this study was to assess the differences of blood perfusion in those who scored in the upper compared to the lower quartiles of mania symptomology. Analyses denoted significant differences in blood perfusion of those with a range of mania symptom severity. Specifically, self-reported mania symptomology appears to be indicative of lower levels of blood perfusion in subcortical regions. These results indicated that SPECT analysis could potentially be useful in the neurological aspect of research on mania symptomology. Ensuing research will aim to distinguish the relationship between brain areas and their associated specific symptoms.

Lenox S, Marsh J, Amen D, Willeumier K, Taylor D, Golden C (2014)
The Activation of the Right Inferior Orbitofrontal Cortex in Individuals with Eating Disorders during Administration of Conners’ Continuous Performance Task.
Read More
Archives of Clinical Neuropsychology, 29(6): 576.


Objective: To investigate the blood flow to the right inferior orbitofrontal cortex in eating disorders during administration of SPECT scans while performing the Conners’ Continuous Performance Task (CPT-I or CPT-II).

Method: Data were collected from the self-reports of clients seen at the Amen Clinic. Participants included 396 individuals with a self-reported diagnosis of an eating disorder, with an average age of 34.41 (SD = 14.03), and 83 normals, with an average age of 41.73 (SD = 16.43). The sample was mostly female, and subtypes of eating disorders were not identified. Participants underwent SPECT scans during performance of the CPT.

Results: Independent t-tests were used to analyze mean differences in blood flow between normals and eating disorders. RESULTS revealed differences in blood flow of the cerebellum and the right inferior orbitofrontal cortex, p < 0.047. No other areas of the brain revealed differences in blood flow while performing the CPT.

Conclusion(s): Individuals with eating disorders showed more blood flow to the right inferior orbitofrontal cortex and cerebellum during the performance of the CPT. Increased blood flow to the right inferior orbitofrontal cortex during the CPT may suggest that individuals with eating disorders may attend more to decision-making in relation to all visual stimuli, not just food and other body-related visual stimuli. Increased blood flow to the cerebellum may suggest that individuals with eating disorders have increased motor control and attention.

Link J, Messerly J, Spearman C, Driskell L, Coad S, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Differences between Those with Higher and Lower Levels of Aggression: An Exploratory Analysis.
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Archives of Clinical Neuropsychology, 29(6): 576.


Objective: To determine which areas of the brain were most associated with level of aggression as measured via SPECT scans.

Method: Participants were selected based on their scores on an aggression factor from a symptom checklist, and had a mean age of 40.97 years (SD = 16.34), and consisted of 56.9% males and 43% females. Subjects were stratified based on upper (n = 2537) and lower (n = 2600) quartiles. Digitally derived blood flow measures from areas throughout the brain were examined at activation.

Results: A MANOVA was conducted at the .05 level, revealing significant group differences, Wilks’ λ = .966; F(16, 6692) = 1.465, p = .001. Those scoring in the upper quartile of the aggression factor yielded significantly lower blood flow than those in the lower quartile in the following areas: amygdala, angular gyrus, calcarine, caudate, specific areas of the cerebellum, cingulum, cuneus, frontal inferior operculum, fusiform, Heschl’s gyrus hippocampus, insula, lingual gyrus, mid and superior occipital lobe, olfactory cortex, globus pallidus, parahippocampal gyrus, parietal lobe, left pre- and post-central gyri, precuneus, putamen, rolandic operculum, supramarginal gyrus, temporal lobe, thalamus, and vermis.

Conclusion(s): Analyses revealed higher levels of self-reported aggression differed significantly in terms of perfusion to various areas relative to lower levels of aggression. These findings suggest many areas mediate symptoms of aggression and that SPECT scans may be a fruitful tool in identifying those susceptible to high levels of aggression. Future research will try to differentiate which areas show the greatest contribution to aggressiveness.

Blose M, Coad S, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Imaging in Adults with Nicotine-Related Disorders.
Read More
Archives of Clinical Neuropsychology, 29(6): 575.


Objective: The study examined whether nicotine disorders affect cerebral blood flow at baseline and while concentrating.

Methods: Two hundred and sixty two individuals with a diagnosis of a nicotine disorder and 94 healthy controls were given a single photon emission computed tomography (SPECT) scan as part of a comprehensive evaluation. Participants included 119 females, 236 males, and one unknown ranging from ages 18 to 84 with an average age of 35.7 (SD = 13.86). Baseline SPECT and SPECT while taking the Connors CPT (activation) were generated.

Results: An independent t-test was conducted, indicating a statistically significant (p < .001) increase in blood flow for individuals with nicotine disorders in the cerebellum, the occipital lobe, and the inferior, anterior region of the temporal lobe as well as the temporal pole at baseline. During the CPT, findings were consistent with baseline for the cerebellum and the temporal lobe, but not the occipital lobe.

Conclusion(s): The SPECT imaging reveals that long-term nicotine use may activate the cerebellum and sections of every lobe, with the entire occipital lobe being stimulated; thus, nicotine appears to have a greater effect on the posterior and the inferior regions. The increased blood flow in the inferior region of the brain is more than likely due to the activation of the nicotinic receptors. This result suggests that chronic nicotine exposure may have an effect on the binding properties of nicotinic acetylcholine receptors. In addition, because of the increased amount of activation in the temporal lobe, these results indicate that nicotine may affect semantic processing.

Zusman M, Amen D, Willeumier K, Taylor D, Golden C (2014)
The Effect of Inattention on Cerebral Blood Flow Perfusion.
Read More
Archives of Clinical Neuropsychology, 29(6): 542.


Objective: This study attempted to differentiate between ADHD patients, primarily inattentive subtype, from a healthy comparison group, using high resolution brain SPECT imaging.

Methods: Participants included 140 patients with ADHD inattentive type and 149 demographically-matched controls. All participants underwent brain SPECT imaging at rest and during concentration using semiquantitative visual readings.

Results: A one-way ANOVA was conducted and revealed significant differences in cerebral blood perfusion, as measured by SPECT scan, between the ADHD group and the healthy controls. Significant differences at the (p < .001) level were observed in 100% of the measured areas of the occipital lobe, 71% of the areas of the frontal lobe, 61% of the cerebellum, 12.5 % of the vermis within the cerebellum, 50% of the parietal lobe, 50 % of the angular gyrus, 50% of the calcarine fissure, and 4.5 % of the temporal lobe. Regions of interest that were insignificant included all measured areas of the amygdala, cuneus, fusiform gyrus, insula, olfactory, palladium, caudate nucleus, putamen, paracentral lobule, and lingual gyrus.

Conclusion(s): Results indicate a significant difference in cerebral blood perfusion for the ADHD inattentive group in several brain areas when compared to a healthy control group. This study shows that compared to a healthy control group, participants diagnosed with the inattentive subtype of ADHD have significantly different perfusion in their frontal, occipital, and parietal lobe, as well as the cerebellum. These results can have important applications when prescribing and developing medication to target attentional difficulties and in developing rehabilitation strategies for those with frontal lobe deficits.

Yassin S, Spengler K, Amen D, Willeumier K, Taylor D, Golden C (2014)
Differences in SPECT Perfusion in Children and Adolescents with ADHD.
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Archives of Clinical Neuropsychology, 29(6): 541-2.


Objective: This study looked at differences in brain function at rest between children and adolescents diagnosed with and without ADHD by using results obtained from single-photon emission computerized tomography (SPECT) scans.

Methods: Participants were 2168 children/adolescents with ADHD (mean age = 12) and 906 children/adolescents without ADHD (mean age = 12). In the ADHD group, 604 were females and 1557 were males, and 1105 were identified as Caucasian (36%). In the non-ADHD group, 309 were females and 593 were males, and 353 (11%) were Caucasians. Differences across all brain regions at baseline were analyzed using SPECT.

Results: A MANOVA found significant differences for the angular gyrus, calcarine fissure, caudate nucleus, cerebellum, cuneus gyrus, frontal lobe, fusiform gyrus, Heschl’s gyrus, lingual gyrus, occipital lobe, paracentral lobule, parahippocampal area, parietal lobe, post central gyrus, precuneus, rolandic operculum, supplementary motor area, supramarginal gyrus, and temporal lobe (p < .001). Frontal and temporal lobes were found to have the highest number of areas that were significantly different between the two groups, with the temporal lobe having the most number of areas with significant differences.

Conclusion(s): The results of this study suggest multiple brain regions are associated in ADHD, particularly the areas of the frontal and temporal lobes. This indicates the functional abilities of the frontal and temporal lobes are implicated in children and adolescents with ADHD which may account for their difficulties in motor control, problem solving, and self-regulation difficulties. However, other brain areas were involved as well indicating, while there is heavy frontal/temporal involvement, it is not restricted to these areas.

Hubbard L, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Imaging Differences in Children with Attention Deficit Hyperactivity Disorder versus Children with Anxiety.
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Archives of Clinical Neuropsychology, 29(6): 541.


Objective: The purpose of this study was to examine whether differences in cerebral blood flow (CBF) exist in children with attention deficit hyperactivity disorder (ADHD) verses children with anxiety while concentrating.

Methods: A clinical sample of 1186 children was selected. Participants included 854 male and female children diagnosed with ADHD (i.e., combined type, mostly inattentive, asymptomatic, and inattentive type) and 332 male and female children who received a diagnosis of anxiety based on DSM-IV criteria. The average age was 12.13 years (SD = 3.54). CBF was measured during administration of the Conners’ Continuous Performance Test (2ndedition) via a SPECT scan. Regions of interest (ROIs) were based on the Automated Anatomical Labeling (AAL) brain atlas.

Results: Using a .05 significant level, t-tests indicated that children diagnosed with ADHD demonstrated greater CBF in 29 ROIs while concentrating. In ADHD children, the majority of the ROIs that demonstrated greater CBF were located in the frontal, temporal, parietal, and occipital lobes and cerebellum with the most significance displayed in the left and right hemispheres of the temporal lobe.

Conclusion(s): SPECT imaging evidenced that differences exist in CBF between children diagnosed with ADHD and children diagnosed with anxiety when presented with a concentration task. The numerous ROIs associated with greater CBF indicate that ADHD children have more active frontal, temporal, parietal, and occipital lobes during concentration than children diagnosed with anxiety in the same brain areas.

Roberts C, Blose M, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Imaging Differences in Adult Males versus Adult Females with Dementia.
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Archives of Clinical Neuropsychology, 29(6): 531.


Objective: The purpose of this study was to examine whether differences in cerebral blood flow (CBF) exist in adult males versus adult females diagnosed with dementia at-rest and while concentrating.

Methods: A clinical sample of individuals aged 65-94 was selected. Participants included 182 males and 145 females who received a diagnosis of dementia (i.e., dementia, delirium, and amnestic disorders) based on DSM-IV criteria. The average age was 74.35 years (SD = 6.56). CBF was measured at rest and during administration of the Connors’ Continuous Performance Test II via a SPECT scan. Regions of interest (ROIs) were based on the Automated Anatomical Labeling (AAL) brain atlas.

Results: Using a .001 significant level, t-tests indicated that adult females demonstrated greater CBF in 73 ROIs at rest and while concentrating. Only minor differences in these ROIs existed between rest and concentration. In adult females, the majority of the ROIs that demonstrated greater CBF were located in the telencephalon, specifically the cerebral cortex, the limbic system, and the basal ganglia. In adult males, the ROIs in the cerebellum were the main areas that demonstrated greater CBF.

Conclusion(s): SPECT imaging evidenced that differences in CBF between adult males and adult females exist within those diagnosed with dementia, specifically, adult females’ telencephalons are more active at rest and during concentration than adult males. This indicates that, within a dementia population, adult females and adult males will manifest behavioral and cognitive symptoms of dementia differently since both groups exhibit significantly different amounts of CBF and cerebral activity.

Blose M, Roberts C, Amen D, Willeumier K, Taylor D, Golden C (2014)
SPECT Imaging Differences in Adults versus Older Adults with Dementia.
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Archives of Clinical Neuropsychology, 29(6): 510.


Objective: To investigate whether age affects cerebral blood flow in individuals with dementia at baseline and while concentrating.

Methods: 709 individuals with dementia diagnosed by DSM-IV criteria were given a single photon emission computed tomography (SPECT) scan as part of a comprehensive evaluation. Participants included 368 males and 341 females. 347 individuals were between the ages of 50 and 64 (49%) and 362 individuals were between the ages of 65 and 94 (51%). Baseline SPECT and SPECT while taking the Connors CPT (activation) were generated. An activation score was generated by subtracting z-scores for the baseline from z-scores for the concentration phase.

Results: At the .001 level, t-tests revealed differences in the younger adults as compared to the older results in multiple regions (20) during activation primarily in the temporal lobe and the supramarginal gyrus. The temporal lobe showed more activation with the greatest activation occurring in the inferior temporal gyrus and the middle temporal gyrus.

Conclusion(s): Based on the SPECT images, there is a decrease in activation in the temporal lobe of the brain in older adults with dementia. During the Connors CPT, cerebral blood flow should be greater due to the attention-related tasks of the assessment. The degree of increase was much smaller in the older dementia subjects showing an increasing inability to increase activity under demand conditions. This would impair the ability to respond to the increased demands of the task.

Willeumier K, Taylor DV, Amen, DG.
Neurobiological correlates of introversion-extraversion with activation-state brain SPECT imaging
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(submitted for publication)

Here we explored the relationship between personality and regional cerebral blood flow using the introversion-extraversion subscale of the Keirsey temperament scale (KTS-II) and brain single-photon computed emission tomography (SPECT) in former professional American football players. We administered the KTS-II to a cohort of 78 (mean age ± SD) retired professional football players who underwent a comprehensive evaluation in an outpatient psychiatric clinic which included SPECT imaging as part of a study measuring the effects of repetitive subconcussive impacts on brain function. Using SPSS, whole brain average and region of interest (ROI) analysis were performed on the subscale of introversion-extraversion (introversion, n=26; extraversion, n=38; mixed, n=8; neither, n=6). Introverts show elevated metabolic activity across multiple brain regions including the anterior cingulate gyrus, caudate, temporal lobes, hippocampus, inferior parietal lobe and the cerebellar vermis IX. Alternatively, extraverts show lower overall global activity, with reductions in the inferior orbital and prefrontal cortices. The present study demonstrates distinct regional activity profiles unique to extraversion and introversion during a brain activation-task which has not been previously reported. Further exploration into mapping the neural pathways that are associated with introversion-extraversion may extrapolate meaningful correlations between these personality dimensions and brain physiology.

Harcourt S, Amen DG, Willeumier K, Golden, C.
Regional cerebral blood flow in schizophrenia while in attention task.
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Presented at the American Psychological Association 2014


Introduction: Blood perfusion patterns may be useful in identifying specific deficits in persons with schizophrenia. This exploratory study uses data from high-resolution single-photon emission computed tomography (SPECT) analysis of regional cerebral blood flow (rCBF) in brain regions of interest (ROI) to seek relationships between rCBF and a clinical diagnosis of schizophrenia while participants are engaged in a selective and sustained attention task. The amygdala, hippocampus, and temporal lobe were chosen as focal points of this study based on prior research.

Methods: Clinical participants were adults presenting for psychiatric care at 8 clinics on both U.S. coasts (n=74; age 18-84, M=40.8; 59% male, 65% White, 42% West Coast) who consented to participation; historical diagnosis was confirmed clinically prior to study. Healthy participants (defined as persons having no mental health disorder, neither historically nor upon clinical assessment) were solicited from a West Coast university (n=46; age 18-84, M=40.8; 46% male, 46% White, 100% West Coast). SPECT scans were made of the left- and right-sided ROIs of the amygdala, hippocampus, and temporal lobe, in a resting state, for baseline values of rCBF. Second, SPECT was conducted in the same areas under a concentration task in which the participant engaged in the Conners’ CPT. Z-scores were computed in each lobe of each ROI (z-scores were used rather than raw scores, due to each ROI having unique statistical descriptors), representing rCBF as an index above or below the mean rCBF for the entire sample. The difference of the concentration z-score and the baseline z score was computed, representing net magnitude and direction of change in blood flow. Positive differences represent increases in flow of blood or rCBF, while negative values are decreases in flow. The full procedure is described elsewhere (Amen, Hanks, & Prunella, 2008).

Results: Six t-tests were performed (3 ROIs in each hemisphere) comparing rCBF in concentration condition minus rCBF at baseline, of participants with schizophrenia to healthy participants; all calculations used a significance criterion of p=.01. The t-tests were significant for: the left amygdala with schizophrenia (M=.053, SE=.072) versus healthy (M=-.54, SE=.20), t(56.921)=-2.8; the right amygdala (M=.082, SE=.077) versus healthy (M=-.62, SE=.19), t(60.011)=-3.4; the left hippocampus with schizophrenia (M=.032, SE=.071) versus healthy (M=-.57, SE=.20), t(56.659)=-2.9; the right hippocampus (M=.082, SE=.065) versus healthy (M=-.65, SE=.19), t(55.583)=-3.6; the right temporal lobe (M=-.098, SE=.064) versus healthy (M=.74, SE=.064), t(59.049)=4.8.

Discussion(s): This exploratory analysis found that the ROIs of the amygdala and hippocampus experienced a decrease in rCBF in moving from baseline to a concentration task, in persons with schizophrenia. In the healthy participants, the flow rate instead increased very slightly. The opposite effects were observed in the temporal lobes, with the schizophrenia group showing small decreases in flow rate, and healthy participants showing increases of up to three-quarters of an SD unit in blood flow. In all cases, the right-side flow increased or decreased from 20% to 900% more than the left side; lateral rate differences were greater in the diagnosed group than the healthy group, and in the temporal lobes more so than the amygdala and hippocampus.

Silverman DH, Willeumier K, Torosyan N, Mallam S, Raji C, Dahlbom M, Amen, DG
Regional cerebral blood flow patterns during performance of an attention-focused cognitive task in patients resistant and responsive to antidepressant therapy.
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Accepted by the Society of Nuclear Medicine Meeting 2014


Objective: To assess regional patterns of cerebral blood flow (rCBF) predictive of therapy-resistant versus therapy-responsive unipolar depression.

Methods: Forty patients with a clinical diagnosis of depression and Beck Depression Inventory (BDI) II score= 25 underwent 99mTc-HMPAO SPECT. Brain images were acquired on a Picker 3-headed camera at rest and during an attention-focusing cognitive task. Half (n=20; av. age 43, range 20-66) were responsive (BDI =13 or reduced by 50% 6 months post-treatment) to therapy, and half (n= 20; av. age 41, 19-59) were non-responsive to therapy. The regional pattern of blood flow in the brain of each patient was assessed by quantification of mean activity in each of 47 standardized volumes of interest, relative to mean whole brain activity, and differences between therapy-resistant and therapy-responsive groups were statistically assessed by two-tailed Student t-test.

Results: There were no significant differences (p>0.3) in BDI II scores between responders (32.6±1.6) and non-responders (30.7±1.0) before therapy. At the end of 6 months of treatment, however, the BDI II score was significantly lower (p<0.00000000003) in responders (7.4±1.0) versus non-responders (26.5±1.8). During the attention-focusing task, the left lentiform nucleus (LN) was the region having rCBF that differed most significantly between responders and non-responders (1.19±0.01 and 1.16±0.01 respectively, p<0.02). No difference was seen in the lLN at resting when comparing responders to non-responders (1.18±0.01 for each). Correspondingly, the lLN was also the region in which the change between the resting and attention-focusing task was most significantly different between therapy-resistant and therapy-responsive groups (p<0.03).

Conclusion(s): Higher level of lentiform nucleus blood flow during an attention-focusing task is predictive of clinical response to anti-depressant therapy.

Amen DG, Mallam S, Torosyan N, Silverman DH, Raji C, Dahlbom M, Willeumier K.
Regional cerebral blood flow (rCBF) patterns distinguishing bipolar mood and attention deficit hyperactivity disorders
(submitted for publication)

Raji C, Amen DG, Torosyan N, Willeumier K, Mallam S, Dahlbom, M, Silverman, DH
Altered regional cerebral blood flow patterns in NFL offensive linemen and defensive backs.
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Accepted by the Society of Nuclear Medicine Meeting 2014


Objective: To examine regional patterns of cerebral blood flow (rCBF) associated with offensive line and defensive back positions played by professional football players.

Methods: A total of 71 men (mean age 57 y.o, range 26-82) with a history of playing in the NFL as offensive linemen (OL, n=44) or as defensive backs (DB, n=27) underwent 99mTc-HMPAO SPECT with a Picker 3-headed camera as they performed the Conners’ Continuous Performance Task-II, an attention-focusing cognitive task. A sex-matched control group of non-players (NC, age range 19-84) was studied under identical conditions. The regional pattern of blood flow in the brain of each player and control subject was assessed by quantification of mean activity in each of 47 standardized volumes of interest, relative to mean whole brain activity, and between-group differences were considered statistically significant after Bonferroni-type correction for multiple comparisons (p = 0.001 before adjustment) by two-tailed Student t-test.

Results: In comparing all players to NC, significant diminished rCBF was seen in the right medial anterior temporal (rMAT, p=0.0007) and left anterior cingulate (lGCa, p=0.0002) regions, and significant elevated rCBF was seen in left lentiform nucleus (lLN, p=0.0000006). The significance of diminished rCBF in lGCa was primarily driven by a 3% decrease among OL (p=0.0002), while only 1% decrease (p>0.10) was seen among DB; significance of diminished rCBF in rMAT was primarily driven by a 4% decrease in DB (p=0.0007). The magnitude of rCBF in lLN reflected significant increases of 2-3% in both DB (p=0.0006) and OL (p=0.000002).

Conclusion(s): History of NFL play is associated with alterations in cerebral blood flow in a regionally specific manner, with significant decreases seen in a medial frontal region important for executive functions in offensive linemen, and in a medial temporal region important for memory function especially in defensive backs.

Newberg AB, Serruya M, Gepte A, Intenzo C, Lewis T, Amen DG, Russell D, Wintering N (2014)
Clinical comparison of 99mTc exametazime and 123I ioflupane SPECT in patients with chronic mild traumatic brain injury.
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PLoS One, 9(3): e91088.


Background: This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population.

Methods and Findings: Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both 99mTc exametazime to measure cerebral blood flow (CBF) and 123I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had higher CBF in the right frontal lobe, right thalamus, and left basal ganglia compared to patients without headaches. Lower CBF in the left frontal lobe and right temporal lobe correlated with poorer reported physical health. Higher DAT bindingwas associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients.

Conclusion(s): Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Raji C, Tarzwell R, Pavel D, Schneider H, Uszler J, Thornton J, van Lierop M, Cohen P, Amen DG, Henderson TA (2014)
Clinical utility of SPECT in the diagnosis and treatment of traumatic brain injury: A systematic review.
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PLoS One, 9(3): e91088.

Traumatic brain injury (TBI) is a devastating problem with serious morbidity and mortality. This systematic review evaluated the global literature for single photon emission computed tomography (SPECT) use in TBI. From 1600 studies identified, 71 articles, 19 longitudinal and 52 cross-sectional studies, met rigorous standardized inclusion criteria. Of these, 100% of longitudinal and 98% of cross sectional studies showed SPECT lesion localization not detected by CT or MRI. Almost 80% of longitudinal and 81% of cross sectional articles showed significant correlation between SPECT and neuropsychological or neurological outcomes. This review highlights the extensive literature base for SPECT in evaluating TBI.


Amen DG, Taylor DV, Ojala K, Willeumier K (2013)
Effects of a brain-directed nutrient system on rCBF and neuropsychological testing: A randomized, double blind, placebo controlled, cross-over trial.
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Advances in Mind-Body Medicine, 27(2): 18-27.


Introduction: In a prior study of professional football players with the effects of traumatic brain injury we reported significant improvements in clinical symptoms, neuropsychological testing, and regional cerebral blood flow (rCBF) as assessed by single photon emission computed tomography (SPECT) in an open trial comprised of brain-directed nutrients (BDNs) and lifestyle interventions. Here, we extend this investigation in healthy individuals using the same BDNs, with a more rigorous design, without lifestyle interventions.

Method: We utilized a randomized, double-blind, placebo-controlled, cross-over trial of 25 individuals to determine whether supplementation with BDNs improves rCBF and neuropsychological function. Primary outcome measures include changes in rCBF using SPECT, differences in cognitive and emotional function assessed using the MicroCog and Webneuro, and psychological inventories (Beck Depression Inventory, BDI-II; Brief Symptom Inventory, BSI; Quality of Life Inventory, QOLI).

Results: Region of Interest analysis showed significant improvement in rCBF compared to placebo in the prefrontal cortex, anterior and posterior cingulate gyrus, hippocampus, and cerebellum. Significant improvements were observed on the Microcog (executive function (0.002), reasoning (0.008), memory (0.014), information processing efficiency (0.015) and accuracy (0.027)), Webenuro, (depressed mood (0.017) and emotional identification (0.041)), and BSI (Positive Symptom Total (0.024) and reduced hostility (0.018)).

Conclusion(s): This study demonstrates the potential effectiveness of BDNs to enhance rCBF and neuropsychological function across various cognitive and psychological domains.

Amen DG, Trujillo M, Keator D, Taylor DV, Willeumier K
rCBF gender differences in a sample of 46,034 SPECT scans
(submitted for publication).

Amen DG, Jourdain M, Taylor DV, Pigott HE, Willeumier K (2013)
Multi-site, six month outcome study of complex psychiatric patients evaluated with addition of brain SPECT imaging.
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Advances in Mind-Body Medicine, 27(2): 4-14.


Background: Psychiatric diagnoses are made primarily through clinical histories searching for DSM driven symptom clusters, and outcomes for patients have not substantially improved in decades for many disorders.

Objective: In this study we examine the outcome impact of the addition of SPECT to the assessment of complex patients.

Methods: In this multi-site, prospective study, all new outpatients from four psychiatric clinics were entered into a 6 month outcome study between January 2011 and August 2012. The study was completed after final outcome measures were obtained on 500 patients. Primary Outcome Measures: Evaluations included histories, mental status examinations, Structured Clinical Interview for DSM-IV (SCID-IV), Beck Depression Inventory-II (BDI-II), Brief Symptom Inventory (BSI), Quality of Life Inventory (QOLI) and rest and concentration brain SPECT scans. At 6 months standardized outcome measurements were re-administered (BDI-II, BSI, QOLI), along with questions about improvement and compliance.

Results: 75% of patients reported significant clinical improvement; 55% reported being “very compliant”, 41% “somewhat compliant” and 4% “non-compliant”. Significant improvements were observed across all 3 assessments (BDI mean difference = -6.92, 360 (72%) subjects decreased; BSI mean difference = -0.38, 367 out of 461 (79%) subjects decreased; QOLI mean difference = +1.65, 427 (85%) subjects improved) at 6 months (Hotelling’s T2 = 460, p < 0.0001). Net improvement was measured at 81% (n=405).

Conclusion(s): To authors’ knowledge this is the first outcome study in complex psychiatric patients using SPECT as an additional diagnostic tool, demonstrating significant improvement. Further studies comparing the addition of brain SPECT to “treatment as usual” groups are warranted.

Amen DG (2013)
It’s time to stop flying blind: How not looking at the brain leads to missed diagnoses, failed treatments, and dangerous behaviors.
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Alternative Therapies, 19(2).

Amen DG: It’s Time to Stop Flying Blind: How Not Looking at the Brain Leads to Missed Diagnoses, Failed Treatments, and Dangerous Behaviors, Alternative Therapies, Epub ahead of print January 14, 2013. http://www.alternative-therapies.com/openaccess/ATHM_19-1_Amen.pdf


Amen DG and Burnett L (2012)
Daniel Amen, MD: The impact of brain imaging on psychiatry and treatment for improving brain health and function.
Alternative Therapies, 18(2): 52-58.

Amen D, Highum D, Licata R, Annibali J, Somner L, Pigott HE, Taylor DV, Trujillo M, Newberg A, Henderson TA, Willeumier K (2012)
Specific ways brain SPECT imaging enhances clinical psychiatric practice.
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Journal of Psychoactive Drugs, 44(2): 96-106.


Introduction: Our objective was to ascertain in a prospective case series how often brain single photon emission computed tomography (SPECT) neuroimaging adds relevant information for diagnosis and/or treatment beyond current standard assessment tools in complex psychiatric cases.

Methods: Charts of 109 consecutively evaluated outpatients from four psychiatrics clinics which routinely utilize SPECT imaging for complex cases were analyzed in two stages. In stage one, psychiatrists reviewed detailed clinical histories, mental status exams, and the Structured Clinical Interview for DSM-IV, but not the results of SPECT studies, and assigned a diagnosis, based on DSM-IV criteria, and then developed a comprehensive treatment plan. In stage two, evaluators were given access to the SPECT studies for each patient. They then determined if the scans added new information to the diagnosis and/or treatment plan recorded in stage one. If SPECT added value, the evaluators categorized it as either: 1) additions and/or changes to the diagnoses and/or 2) additions and/or changes to the clinical management.

Results: The addition of SPECT modified the diagnosis or treatment plan in 78.9% (n=86; rated level 2 or 3 change) of cases. The most clinically significant changes were undetected brain trauma (22.9%), toxicity patterns (22.9%) and the need for a structural imaging study (9.2 %). Specific functional abnormalities were seen as follows that potentially could impact treatment: temporal lobe dysfunction (66.1%) and prefrontal hypoperfusion (47.7%).

Conclusion(s): SPECT has the potential to add clinically meaningful information to enhance patient care beyond current assessment tools in complex or treatment resistant cases.

Amen DG, Willeumier K, Johnson R (2012)
The clinical utility of brain SPECT imaging in process addictions.
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Journal of Psychoactive Drugs, 44(1): 18-26.

Brain SPECT imaging is a nuclear medicine study that uses isotopes bound to neurospecific pharmaceuticals to evaluate regional cerebral blood flow (rCBF) and indirectly metabolic activity. With current available technology and knowledge SPECT has the potential to add important clinical information to benefit patient care in many different areas of a substance abuse practice, including in the area of process addictions. This article explores the ways brain SPECT has the potential to be useful to clinicians in helping to understand and direct treatment for complex cases of obesity and sexual addictions. Areas where SPECT can add value include helping clinicians ask better questions, helping them in making more complete diagnoses, evaluating underlying brain systems pathology, decreasing stigma and increasing compliance, and visualizing effectiveness via follow-up evaluations. In particular, SPECT can help identify and assess the issue of brain trauma and toxicity in process addictions, which may be significant contributing factors in treatment failure. Three illustrative case histories will be given.

Willeumier K, Taylor D, Amen D (2012)
Elevated body mass in National Football League players linked to cognitive impairment and decreased prefrontal cortex and temporal pole activity.
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Transl Psychiatry, 2(1): e68.

Obesity is a risk factor for neurodegenerative disease and has been shown to adversely affect cognitive function. Professional athletes who participate in sports which expose them to repetitive concussions may be at heightened risk for cognitive impairment. Here, we investigated the effects of body mass as measured by waist to height ratio (WHtR) on regional cerebral blood flow using SPECT imaging in 38 healthy weight (WHtR mean 49.34% ± 2.8; age 58 ± 9.6) and 38 overweight (WHtR mean 58.7% ± 4.7; age 58 ± 13.3) retired NFL football players. After matching for age and position, we used a 2 sample t-test to determine the differences in blood flow in healthy versus overweight subjects. Statistical parametric mapping (SPM) revealed a higher WHtR ratio is associated with decreased blood flow in Brodmann Areas 8, 9, 10 brain regions involved in attention, reasoning and executive function (P<0.05, family-wise error) along with deficits in the temporal pole. Moreover, overweight athletes had significant decreases in attention (P = 0.01326), general cognitive proficiency (P = 0.012; Microcog: Assessment of Cognitive Functioning (MACF)) and memory (P = 0.005; Mild Cognitive Impairment Screen (MCIS)). The association between elevated WHtR percentage and decreased blood flow in the prefrontal cortex and temporal pole may be correlated with the decreased performance on tests of attention and memory. These findings suggest a weight management program may be critical to the health of athletes who have been exposed to mild brain trauma during their careers.

Harch PG, Andrews SR, Fogarty EF, Amen D, Pezzullo JC, Lucarini J, Aubrey C, Taylor DV, Staab PK, Van Meter KW (2012)
A Phase I study of low pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and posttraumatic stress disorder.
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J Neurotrauma, 29(1): 168-185.


Objective: This is a preliminary report on the safety and efficacy of 1.5 ATA HBOT in military subjects with chronic blast-induced mild-moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD).

Methods: 16 military subjects received forty 1.5 ATA/60 minute HBOTs in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, neuropsychological and psychological testing were completed before and within one week after treatment.

Results: subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post treatment testing demonstrated significant improvement in: symptoms, neurological exam, Full scale IQ (+14.8 points; p=.001), WMS IV Delayed Memory (p<.026), WMS-IV Working Memory (p=.003), Stroop Test (p=.001), TOVA Impulsivity (p=.041), TOVA Variability (p<.045), Grooved Pegboard (p=.028), PCS symptoms (Rivermead PCSQ: p=.0002), PTSD symptoms (PCL-M: p<.001), Depression (PHQ-9: p<.001), Anxiety (GAD-7: p<.007), quality of life (MPQoL: p<.003), and self-report of percent of normal (p<.001),SPECT coefficient of variation in all white matter and some gray matter ROI’s after the first HBOT, and in half of white matter ROIs after 40 HBOT’s, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow).

Conclusion(s): Forty 1.5 ATA HBOTs in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality of life measurements, with concomitant significant changes/normalization of SPECT. Further study of the efficacy and safety of 1.5 ATA HBOT is underway in a larger group of subjects.

Harch P, Andrews SR, Fogarty E, Amen DG, Lucarini J, Van Meter KW (2012)
Response to Letter to the Editor by Wortzel and Colleagues.
J Neurotrauma, 29(14): 2425-2430.


Amen DG, Willeumier K (2011)
Brain SPECT imaging: A powerful, evidence-based tool for transforming clinical psychiatric practice.
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Minerva Psichiatrica, 52(3): 109-23.

Over the past 20 years brain single photon emission computed tomography (SPECT) imaging has developed a substantial, evidence-based foundation and is now recommended by professional societies for numerous indications relevant to psychiatric practice, including dementia, brain trauma, cerebrovascular disease, seizures and complex neuropsychiatric presentations. Unfortunately, SPECT in clinical practice is utilized by only a very small fraction of psychiatric clinicians. This invited article presents a rationale for a more widespread use of SPECT in clinical practice, especially for complex cases, and includes seven clinical applications where it may be immediately helpful in clinical cases.

Willeumier K, Taylor D, Amen D (2011)
Decreased cerebral blood flow in the limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides.
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Translational Psychiatry, 1(8): e28.

Suicide has a high comorbidity with impulsivity and depression, and finding imaging biomarkers indicative of patients at high-risk for suicidal behavior is invaluable to the clinician. Using single-photon emission computed tomography (SPECT) imaging, we have previously reported regional cerebral blood flow (rCBF) decreases in the medial prefrontal cortex, ventral tegmental area, and subgenual cingulate cortex (Brodmann Area 25), a region found to be hypoperfused with treatment-resistant depression. From 2007-2010, we have extended our analysis to include nine additional completed suicides. Twenty-seven healthy, age-gender matched subjects from a previously acquired healthy brain study served as controls to our twenty-one completed suicides. All twenty-one suicides had been previously diagnosed with depression according to DSM-IV criterion. Voxel-by-voxel analyses were performed using statistical parametric mapping (SPM) to compare the differences in 99mTc-HMPAO brain uptake between the groups. Factor analysis of the data identified the top ten regions of hypoperfusion in the suicidal group including the bilateral superior frontal lobes, the right precuneus, the rolandic operculum, postcentral gyrus, left caudate and insular cortex. We also demonstrate more focal decreases in rCBF in the subgenual cingulate cortex (BA 25) in eighteen subjects, supporting our previous hypothesis that hypoperfusion of BA 25 may be a risk factor for suicide in depressed patients. This work suggests that SPECT might be useful in predicting suicidal tendencies in subjects with depression or treatment-resistant depression. Further investigation of this work is necessary to better understand the predictive value of this finding.

Amen DG, Trujillo M, Newberg A, Willeumier K, Tarzwell R, Wu JC, Chaitin B (2011)
Brain SPECT imaging in complex psychiatric cases: An evidence-based, underutilized tool.
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Open Journal of Neuroimaging, 5: 40-48.

Over the past 20 years brain Single Photon Emission Computed Tomography (SPECT) imaging has developed a substantial, evidence-based foundation and is now recommended by professional societies for numerous indications relevant to psychiatric practice. Unfortunately, SPECT in clinical practice is utilized by only a handful of clinicians. This article presents a rationale for a more widespread use of SPECT in clinical practice for complex cases, and includes seven clinical applications where it may help optimize patient care.

Willeumier K, Taylor D, Amen D (2011)
Elevated BMI is associated with decreased blood flow in the prefrontal cortex using SPECT imaging in healthy adults.
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Nature Obesity, 19(5): 1095-7.


Context: Obesity is a risk factor for stroke and neurodegenerative disease. Excess body fat has been linked to impaired glucose metabolism, insulin resistance and impulsivity and may be a precursor to decline in attention and executive cognitive function.

Objective: To investigate the effects of high body mass index on regional cerebral blood flow (rCBF) using SPECT imaging in healthy brain subjects.

Design, setting, and participants: We used SPECT imaging data and analyzed changes in rCBF from 16 adult men and 20 adult women recruited from the community as part of a healthy brain study conducted at the Amen Clinics Inc., a private medical facility, from May 2008 to May 2010. Participants in the study were screened for neurological and psychiatric conditions, concussion history and substance use and excluded based on any conditions known to affect brain function. An additional inclusion criterion for the study was scoring normal on the Connor’s Continuous Performance Test (C-CPT II), an assessment of attention. Subjects were categorized as normal or overweight according to body mass index (BMI). We used a 2 sample t-test to determine the effects of BMI on rCBF. Subjects were matched for age and gender. Main outcome measure: Changes in rCBF in normal and overweight adults. Normal was defined as a BMI of 24.9 or lower. Overweight was defined as a BMI of 25.0 or higher.

Results: Higher BMI in healthy individuals is associated with decreased rCBF in Broadmann Areas 8, 9, 10, 11, 32 and 44, brain regions involved in attention, reasoning and executive function (P<0.05, FEW).

Conclusion(s): We found an elevated BMI is associated with decreased rCBF in the prefrontal cortex of a healthy, middle-aged cohort. These findings indicate that elevated BMI may be a risk factor for impaired executive function and planning, issues associated with the prefrontal cortex.

Amen DG, Wu JC, Taylor D, Willeumier K (2011)
Reversing brain damage in former NFL players: Implications for TBI and substance abuse rehabilitation.
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Journal of Psychoactive Drugs, 43(1): 1-5.


Objective: Brain injuries are common in professional American football players, and their incidence has been associated with mild cognitive impairment, dementia, substance abuse and depression. Finding effective brain rehabilitation strategies is essential to helping retired players live more effective lives. In addition, if brain injury rehabilitation strategies can be found, it potentially has widespread implications for the traumatic brain injury and substance abuse communities whose patient also experience long standing brain damage.

Design: Open label, “pragmatic,” clinical intervention Subjects: 30 retired NFL players, a subset of a larger group of 100 players in a brain imaging and neuropsychological testing study Interventions: An open-label, pragmatic, clinical intervention study, which included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was 6 months. Outcome Measures: Microcog Assessment of Cognitive Functioning and brain SPECT imaging.

Results: In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum.

Conclusion(s): This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions. Randomized, placebo-controlled studies evaluating the individual interventions are warranted in this population.

Amen DG, Newberg A, Thatcher R, Jin Y, Wu J, Keator D, Willeumier K (2011)
Impact of playing American professional football on long term brain function.
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Journal of Neuropsychiatry and Clinical Neurosciences, 23(1): 98-106.

We recruited 100 active and former NFL players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including Microcog. Compared to a normal control group players showed global decreased perfusion, especially in the prefrontal, temporal lobe, parietal, occipital and cerebellar regions. qEEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.


Newberg AB, Wintering N, Waldman MR, Amen D, Khalsa DS, Alavi A (2010)
Cerebral blood flow differences between long-term meditators and non-meditators.
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Conscious Cogn, 19(4): 899-905.

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow (CBF) SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators was significantly higher (p<.05) compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function.

Amen D (2010)
Brain SPECT imaging in clinical practice.
Am J Psychiatry, 167(9): 1125.


Khalsa DS, Amen D, Hanks C, Money N, Newberg A (2009)
Cerebral blood flow changes during chanting meditation.
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Nucl Med Commun, 30(12): 956-61.


Objective: To examine changes in brain physiology during a chanting meditation practice using cerebral blood flow single-photon emission computed tomography.

Methods: Single-photon emission computed tomography scans were acquired in 11 healthy individuals during either a resting state or meditation practice randomly performed on two separate days. Statistical parametric mapping analyses were conducted to identify significant changes in regional cerebral blood flow (rCBF) between the two conditions.

Results: When the meditation state was compared with the baseline condition, significant rCBF increases were observed in the right temporal lobe and posterior cingulate gyrus, and significant rCBF decreases were observed in the left parieto-temporal and occipital gyri.

Conclusion(s): The results offer evidence that this form of meditation practice is associated with changes in brain function in a way that is consistent with earlier studies of related types of meditation as well as with the positive clinical outcomes anecdotally reported by its users.

Amen DG, Prunella JR, Fallon JH, Amen B, Hanks C (2009)
A comparative analysis of completed suicide using high resolution brain SPECT imaging.
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The Journal of Neuropsychiatry and Clinical Neurosciences, 21: 430–439.

The authors compared regional cerebral blood flow in the brains of 12 psychiatric patients who completed the act of suicide with groups of healthy and non-suicidal depressed subjects using statistical parametric mapping. Results were consistent with prior imaging studies on depression and were indicative of impaired impulse control and limbic dysregulation, including significant perfusion deficits in the medial prefrontal and subgenual areas (Brodmann’s areas 11, 25) and ventral tegmentum. These results warrant further research.


Boersma N, Wiersma J, Hanks C, Huijsmans M, van Isselt H, Amen D (2008)
Cerebral blood flow in TBI patients: SPM analysis of HMPAO-SPECT.
Presented at the World Congress on Brain Injury in Lisbon, Portugal April 2008

Amen DG, Hanks C, Prunella, J (2008)
Predicting positive and negative treatment responses to stimulants with brain SPECT imaging.
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Journal of Psychoactive Drugs, 40(2): 131-8.

The goal of this study was to test whether clinician-rated regional cerebral blood flow (rCBF) as rendered by SPECT imaging is a meaningful predictor of patient response to CNS stimulants. Chart reviews were used to identify patients who reported prior significant positive and negative responses to CNS stimulants. Each patient in the study had received resting and concentration SPECT scans using Tc99m exametazime. Differences in cerebral blood flow for frontal regions of interest were assessed in three conditions (resting, concentration, and their difference, or “delta”) using ANCOVAs and age-matched ANOVAs. Prefrontal pole deltas were found to be highly sensitive and specific predictors of response to CNS stimulants, with pole activation predicting adverse responses and pole deactivation predicting good responses. Positive and negative predictive values were greater than .75 for both poles. We conclude that SPECT renderings of rCBF, particularly in the prefrontal cortex, are a potentially powerful clinical tool for anticipating response to stimulant medications, both positive and adverse.

Amen DG, Hanks C, Prunella, J (2008)
Preliminary evidence differentiating ADHD from healthy controls using brain SPECT imaging in older patients.
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Journal of Psychoactive Drugs, 40(2): 139-46.

The objective of this study was to differentiate ADHD patients from a healthy comparison group using high resolution brain SPECT imaging in older patients. Using extensive chart reviews of structured interviews, DSM-IV criteria, and psychiatrist-given diagnoses, we identified 27 patients over age 50 with ADHD, either combined or inattentive types. Patients were compared to an age-matched group of healthy subjects with brain SPECT imaging at rest and during concentration using semiquantitative visual readings. Significantly lower cortical activity is noted in the ADHD group, particularly in the prefrontal poles, orbits, and parietal lobes. Older ADHD patients can be discerned from healthy subjects using brain SPECT. The results support the executive dysfunction model of ADHD.

Shankle WR, Hara J, Bjornsen L, Gade GF, Leport PC, Ali MB, Kim J, Raimo M, Reyes L, Amen D, Rudy L, O’Heany T (2008)
Omentum transposition surgery for patients with Alzheimer’s disease: a case series.
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Neurol Res, 30(3): 313-25.


Objective: To examine effect of omentum transposition surgery (OT) in Alzheimer’s disease (AD).

Methods: Within-subjects design, also known as repeated-measures design, was used. OT was performed on six biopsy-confirmed AD patients (three to the left and right hemispheres each). Follow-up was conducted over 16-50 months. Outcome measures included the sum of the sub-scores of the clinical dementia rating scale (CDRSS), dementia severity rating scale (DSRS), mini-mental status exam (MMSE) and neuropsychiatric inventory (NPI), all normalized to 0-1.0. Outcomes were compared to baseline values and to expected decline with and without cholinesterase inhibitors therapy (ChEI).

Results: Compared to baseline and to expected decline with ChEI, CDRSS scores were 22 and 39% less impaired at means of 14 and 25 months post-OT, and DSRS scores were 12 and 22% less impaired at means of 14 and 19 months post-OT (p<0.0001). Compared to baseline and expected course with and without ChEI, the MMSE scores of the left hemisphere OT patients were not significantly different for 11, 17 and 22 months respectively (p>0.49), while those of the right hemisphere OT patients more rapidly declined. The two patients with significant pre-operative behavioral problems markedly improved; NPI severity scores decreased by 23 (16%) and 78 (54%) points and were sustained for 22 and 42 months.

Discussion(s): OT yielded cognitive, functional or behavioral improvement for up to 3.5 years in these AD patients. Compared to randomized ChEI clinical trials, OT was 34 times more likely to produce clinically significant improvement. Basic research to identify the mechanisms underlying the therapeutic effect of omentum is warranted.


Amen DG, Hanks C, Prunella, JR, Green, A (2007)
An analysis of regional cerebral blood flow in impulsive murderers using single photon emission computed tomography.
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J Neuropsychiatry ClinNeurosci, 19(3): 304-9.

The authors explored differences in regional cerebral blood flow in 11 impulsive murderers and 11 healthy comparison subjects using single photon emission computed tomography. The authors assessed subjects at rest and during a computerized go/no-go concentration task. Using statistical parametric mapping software, the authors performed voxel-by-voxel t tests to assess significant differences, making family-wide error corrections for multiple comparisons. Murderers were found to have significantly lower relative rCBF during concentration, particularly in areas associated with concentration and impulse control. These results indicate that non-emotionally laden stimuli may result in frontotemporal dysregulation in people predisposed to impulsive violence.


Amen DG (2006)
Brain imaging in clinical practice: Pro/con: pro position.
Clinical Psychiatry News, September.


Lansing K, Amen DG, Hanks C, Rudy L (2005)
High resolution brain SPECT imaging and EMDR in police officers with PTSD.
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J Neuropsychiatry ClinNeurosci, 17(4): 526-32.

Eye movement desensitization and reprocessing (EMDR) has been shown to be an effective treatment for posttraumatic stress disorder (PTSD). In this study, the authors evaluated the effectiveness and physiological effects of EMDR in police officers involved with on-duty shootings and who had PTSD. Six police officers involved with on-duty shootings and subsequent delayed-onset PTSD were evaluated with standard measures, the Posttraumatic Stress Diagnostic Scale, and high-resolution brain single photon emission computed tomography (SPECT) imaging before and after treatment. All police officers showed clinical improvement and marked reductions in the Posttraumatic Stress Diagnostic Scale Score (PDS). In addition, there were decreases in the left and right occipital lobe, left parietal lobe, and right precentral frontal lobe as well as significant increased perfusion in the left inferior frontal gyrus. In our study EMDR was an effective treatment for PTSD in this police officer group, showing both clinical and brain imaging changes.


Amen DG, Wu JC, Carmichael B (2003)
The clinical use of brain SPECT imaging in neuropsychiatry.
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Alasbimn Journal, 5(19).

This article reviews the literature on brain SPECT imaging in brain trauma, dementia, and temporal lobe epilepsy. Brain SPECT allows clinicians the ability to view cerebral areas of healthy, low, and excessive perfusion. This information can be correlated with what is known about the function or dysfunction of each area. SPECT has a number of advantages over other imaging techniques, including wider availability, lower cost, and high quality resolution with multi-headed cameras. There are a number of issues that compromise the effective use of SPECT, including low quality of some imaging cameras, and variability of image rendering and readings.


Amen DG (2001)
Why don’t psychiatrists look at the brain: the case for the greater use of SPECT imaging in neuropsychiatry.
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Neuropsychiatry Reviews, 2(1): 19-21.

Psychiatrists are the only medical specialists who rarely look at the organ they treat. The odds are that if a patient is having serious problems with feelings (e.g., depression), thoughts (e.g., schizophrenia), or behavior (e.g., violence), the psychiatrist will never order a brain scan. He or she will prescribe medication, psychotherapy, electroconvulsive therapy, or a host of other treatments that will change brain function—but will not know which areas of the patient’s brain work well, which areas work too hard, and which do not work hard enough. In my opinion, the lack of brain imaging has kept psychiatry behind medicine’s other specialties, reducing our effectiveness with patients and hindering our efforts to reduce stigma and improve compliance.

Amen DG (2001)
Brain SPECT imaging in the assessment and treatment of aggressive behavior: A putative “Reward Deficiency Syndrome (RDS)” behavioral subtype.
Abstract of presentation at the First Conference on “Reward Deficiency Syndrome:” Genetic Antecedents and Clinical Pathways, Northern California, November 12-13, 2000, in Molecular Psychiatry, Vol. 6 Supp. 1: S7.

Amen DG (2001)
Attention, doctors.
Newsweek, Feb 26; 137(9): 72-3.


French AP, Amen DG (1999)
Criminal recidivism as a neurobehavioral syndrome.
J Am Acad Child Adolesc Psychiatry, 38(9): 1070-1.

Amen DG (1999)
Regional cerebral blood flow in alcohol induced violence: A case study.
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Journal of Psychoactive Drugs, 31: 4.

A case is presented of a 20-year-old man who became violent on many occasions after ingesting alcohol. On one occasion he committed an armed robbery. Two brain SPECT studies were performed: one when he was alcohol free, and one after he ingested alcohol in the same pattern as the night of the crime. The “alcohol free” study revealed marked hyperactivity in the cingulate gyrus, right and left lateral frontal lobes, right and left lateral parietal lobes and the right lateral temporal lobe. The “alcohol intoxication” study showed an overall dampening effect on the hyperactive areas of the brain, with only the anterior cingulate gyrus showing excessive activity. In addition, the right and left prefrontal cortex became hypoperfused, decreasing impulse control and judgment, as did the left and right temporal lobes, increasing the likelihood for aggression. This study suggests that this man may have been “self-medicating” an overactive brain, but in the process induced a state that increased the likelihood for aggressive behavior. This case study suggests the need for further research in the area of alcohol-induced violence and the potential usefulness of SPECT imaging, although no conclusions can be drawn from one case.

Amen DG (1998)
Brain SPECT imaging in psychiatry.
Primary Psychiatry, 5(8): 83-90.

Amen DG (1998)
Attention deficit disorder: A guide for primary care physicians.
Primary Psychiatry, 5(7): 76-85.

Amen DG, Waugh M (1998)
High resolution brain SPECT imaging in marijuana smokers with AD/HD. Journal of Psychoactive Drugs
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30(2): 1-13.

Marijuana abuse is common among young Americans and even more common among teenagers and adults with attention deficit/hyperactivity disorder (AD/HD). Many teenagers and young adults believe that marijuana is a safe substance to use despite a number of studies demonstrating cognitive impairment with chronic or heavy usage. Brain single photon emission computer tomography (SPECT) imaging is being used increasingly in psychiatry to study underlying functional brain problems, including AD/HD. SPECT provides information on cerebral blood flow and metabolic function. Brain SPECT studies were performed on 30 heavy marijuana users (who had used on at least a weekly basis for a minimum of one year) with AD/HD from an outpatient psychiatric clinic and 10 AD/HD control group subjects matched for age and sex who had never used drugs. The three-dimensional surface images were used in the analysis of the scans, and were blindly interpreted without knowledge of the clinical data. Decreased perfusion in the prefrontal cortex was the only abnormality seen in the AD/HD control group (80%). In the marijuana group, there was a similar decrease in the perfusion of the prefrontal cortex while performing the same concentration task (83%). However, the marijuana group also demonstrated marked decreased activity in the right and left temporal lobes. The severe and moderate ratings were found in the heaviest users, but not necessarily the longest users. This study demonstrates decreased cerebral perfusion in the temporal lobe regions of the brain on SPECT imaging from chronic marijuana usage.

Amen DG, Yantis S, Trudeau J, Stubblefield MS, Halverstadt JS (1997)
Visualizing the firestorms in the brain: An inside look at the clinical and physiological connections between drugs and violence using brain SPECT imaging.
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Journal of Psychoactive Drugs, 29(4): 307-319.

The connection between drugs and violence has been well documented. Understanding the intricacies of this connection is essential to finding effective interventions. Much has been written about the psychosocial causes of these problems, but there have been few studies exploring the biophysiological interface between drug effects, violent behavior and brain metabolism. Over the past eight years, The Amen Clinic has been extensively involved in the clinical use of brain SPECT imaging to evaluate complicated neuropsychiatric problems, especially related to the issues of both violence and substance abuse. From this work several clinical patterns, as well as brain SPECT imaging patterns, have been recognized that may help further our understanding of these problems. In this article, following a brief review of the literature on drugs, violence and the brain, five clinical examples are explored; the authors show how these support the clinical utility of incorporating SPECT imaging into psychiatric assessment of drug abuse and violence. Finally, a model is proposed to help explain the complex interaction between the brain, violence and drug abuse.

Amen DG, Carmichael B (1997)
Oppositional children similar to OCD on SPECT: Implications for treatment.
Journal of Neurotherapy, 2(2): 1-6.

Amen DG, Waugh ME (1997)
Three years on clomipramine: Before and after brain SPECT study.
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Ann Clin Psychiatry, 9(2): 113-116.

A case is presented of a patient diagnosed with attention deficit disorder, obsessive thinking, anger outbursts, and depression who had a SPECT study prior to treatment and after 3 years of treatment on clomipramine. The follow-up SPECT study showed marked improvement overall in the cerebral perfusion of the brain. At rest marked overactivity was noted in the anterior medial aspects of the frontal lobes, along with “patchy” (increased and decreased) uptake throughout the cortical and subcortical areas of the brain. After treatment for 3 years on clomipramine at 225 mg a day, the follow-up SPECT study revealed a normalization of activity in the anterior medial aspects of the frontal lobes as well as no patchy uptake cortically and subcortically as noted in the study prior to treatment. The clinical usefulness of the SPECT study as it relates to this case is discussed.

Amen DG, Carmichael B (1997)
High resolution brain SPECT imaging in ADHD. Ann Clin Psychiatry
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9(2): 81-86.

Children and adolescents with ADHD were evaluated with high-resolution brain SPECT imaging to determine if there were similarities between reported PET and QEEG findings. Fifty-four children and adolescents with ADHD by DSM-III-R and Conners Rating Scale criteria were evaluated. A non-ADHD control group was also studied with SPECT. Two brain SPECT studies were done on each group, a resting study and an intellectual stress study done while participants were doing a concentration task. Sixty-five percent of the ADHD group revealed decreased perfusion in the prefrontal cortex with intellectual stress, compared to only 5% of the control group. These are findings consistent with PET and QEEG findings. Of the ADHD group who did not show decreased perfusion, two-thirds had markedly decreased activity in the prefrontal cortices at rest.

Amen DG (1997)
Criminal recidivism as a neurobehavioral syndrome.
J Am Acad Child Adolesc Psychiatry, California State University Stanislaus, December issue, 23-29.

Amen DG (1997)
Windows into the ADD mind: Essential knowledge base for educators.
School of Education Journal, California State University Stanislaus, December issue, 23-29.

Amen DG (1996)
High resolution brain SPECT imaging in psychiatry provides real help for patients.
Diagnostic Imaging, 85-88.

Amen DG (1996)
Brain SPECT imaging in psychiatric practice.
Advance for Radiological Professionals, 9(16): 12-13.

Amen DG, Stubblefield M, Carmichael B, Thisted R (1996)
Brain SPECT findings and aggressiveness.
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Ann Clin Psychiatry, 8(3): 129-137.

Forty adolescents and adults who exhibited aggressive behavior within the six months prior to evaluation by physically attacking another person or destroying property were evaluated with brain SPECT imaging. A control group of 40 psychiatric patients who had never been reported to exhibit aggressive behavior were also studied. The brain SPECT studies were read blind to aggressiveness by nuclear physician on two separate occasions. The inter-reading reliability was very high. The brain SPECT patterns of the group with aggressive behavior showed significant differences from the control group in several areas of brain. These findings were most often seen in the following combination: decreased activity in the prefrontal cortex, increased activity in the antero-medial portions of the frontal lobes, left-sided increased activity in the basal ganglia and/or limbic system in comparison to the whole brain and focal abnormalities in the left temporal lobe. These findings indicate a possible cerebral perfusion profile for those who exhibit violent or aggressive behavior. Several case studies and the implications for treatment are discussed.

Amen DG, Paldi F, Thisted RA (1993)
Brain SPECT imaging and ADHD.
J. Am. Acad. Child Adolesc Psychiatry (Letter), 32(5): 1079-1080.

Wain HJ, Amen D, Jabbari B (1990)
The effects of hypnosis on a Parkinsonian tremor: a case report with polygraph/EEG recordings.
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Am J ClinHypn, 33(2): 94-8.

Although Parkinsonian tremors typically disappear during sleep and are reduced during relaxation periods, the effects of hypnosis on this type of movement disorder have been generally ignored. We observed a patient’s severe Parkinsonian tremor under hypnosis and monitored it with EEG and EMG studies. The patient was taught self-hypnosis and performed it three to four times daily in conjunction with taking medication. The results suggest that daily sessions of self-hypnosis can be a useful therapeutic adjunct in the treatment of Parkinsonian tremors.


Amen DG, Jellen L, Merves E, Lee RE (1988)
Minimizing the impact of deployment separation on military children: Stages, current preventive efforts, and system recommendations.
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Military Medicine, 153(9): 441-6.

Discusses factors that most influence the adjustment of the child to parent absence in military families. Interactional patterns between family members that affect children (preschoolers to adolescents) during the pre-deployment, deployment, and post-deployment stages are delineated. Preventive measures that have been found to be helpful for parents to use to minimize the negative effects of parent absence are given. How the military could further minimize the impact of deployment separation on children is examined.

Amen DG (1987)
The target theory of suicide: Ideas on evaluating the need for hospitalization.
Resident and Staff Physician. This paper was awarded the General William C. Menninger Memorial Award for the best paper presented by a psychiatric resident at the annual General William C. Menninger Military Psychiatry Course 1985. The award was presented by Karl Menninger, M.D.

The Psychiatrist at Work.
Published by Psychiatry in Industry committee of the Group for the Advancement of Psychiatry; Dr. Amen served on this committee and contributed to the writing of this monograph.


Amen DG (1986)
Emotional aspects of surgery.
Resident and Staff Physician, 32(1): 76-87.

Harden J, Hales RE, Amen D, Lewis G, Miliken C, Orman D (1986)
Inpatient participation in treatment planning: a preliminary report.
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General Hospital Psychiatry, 8(4): 287-90.

This study investigated the effect of patient participation in treatment planning conferences (TPCs) upon length of hospitalization and upon the frequency of military soldiers being returned to duty. Patients with major affective disorders and schizophrenic disorders showed an 8.2% decrease in hospital stay whereas patients with minor affective disorders, personality disorders, substance abuse, and adjustment disorders showed a 98.8% increase. Additionally, the percentage of active duty soldiers with a major depressive episode who were returned to duty increased significantly when they participated in their TPC.

Wain HJ, Amen DG (1986)
Emergency room use of hypnosis.
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General Hospital Psychiatry, 8(1): 19-22.

Myths about hypnosis have interfered with its use in emergency settings. Specifically, included are myths about who induces the hypnotic state, the length of induction time, and the traumatized patient’s inability to concentrate on a focal point. It is suggested, however, that altered states of awareness occur rapidly and spontaneously in the patient who has experienced acute trauma and/or pain. Two cases are presented that illustrate spontaneous trancelike states occurring in traumatic situations. The cases also show how the recognition of these altered states can facilitate the patient’s care and treatment in an emergency setting.

Wain HJ, Amen DG (1986)
The use of hypnosis in EPS-associated anxiety.
Letter to the Editor in Journal of Clinical Psychiatry, 47(2): 98.

Amen DG (1985)
Post Vietnam stress disorder: A metaphor for current and past life events.
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American Journal of Psychotherapy, 43(4): 580-586. First Prize winner of the Baltimore-D.C. Institute for Psychoanalysis essay contest, Nov.1984.

Delayed posttraumatic stress reactions are often triggered by events that echo the original trauma. It is not uncommon, however, for these delayed reactions to represent a metaphor for other current or past life events. A case is presented that illustrates the diagnostic and therapeutic significance of understanding these reactions as a metaphor.

Wain HJ, Amen DG, Oetgen WJ (1984)
Cardiac arrhythmias and hypnotic intervention: Advantages, disadvantages, precautions, and theoretical considerations.
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American Journal of Clinical Hypnosis, 27(1): 70-75.

Hypnotic intervention as an adjunctive therapeutic modality in medical patients has been well documented. Yet, it has not been used as frequently or productively as one would anticipate, perhaps this is due to a lack of reports or publications on this subject. We present the use of hypnotic intervention in a case of ventricular tachycardia that was uncontrolled on numerous drug regimens. The advantages in this patient from the hypnotic intervention included lessening ectopic beats, increased exercise tolerance, possibly breaking an arrhythmic pattern, and increasing the patient’s sense of participation in his treatment. Disadvantages were also present and most notably included a blocking of the patient’s awareness that an arrhythmia was present, which deviated from his previous pattern, and may have been facilitated by the dissociative strategy used. We suggest the need for well designed, prospective studies in this area to determine the overall usefulness of hypnosis in cardiac patients.

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