Honors & Awards

  • Mentored Career Development Award (K01), NIMH (2013-2016)
  • Fellowship in Child and Adolescent Psychiatry Award, Klingenstein Third Generation Foundation (2004-2007)
  • Young Investigator Award, NARSAD (2003-2005)
  • Individual National Research Service Award (F32), NIMH (1997-1999)

Boards, Advisory Committees, Professional Organizations

  • Affiliated Faculty, Stanford Neurosciences Institute (2014 - Present)

Professional Education

  • Ph.D., Wake Forest University, Neuroscience
  • B.S., University of Illinois, Aerospace Engineering

Research & Scholarship

Current Research and Scholarly Interests

I use neuroimaging to investigate changes in brain function associated with behavioral and pharmacological treatments for pediatric psychiatric disorders.

Clinical Trials

  • Brain Response to Treatment for Pediatric PTSD Not Recruiting

    This study will examine how brain activation changes as a result of behavioral treatment for posttraumatic stress disorder (PTSD) in adolescents. The investigators will conduct functional magnetic resonance imaging (fMRI) scans before and after the widely-used trauma-focused cognitive behavioral therapy to better understand how the brain recovers from illness. This study will provide much needed information about brain abnormalities in abused youth, and could lead to improvements in behavioral treatments for patients who do not respond to current treatments.

    Stanford is currently not accepting patients for this trial. For more information, please contact Amy Garrett, 650-736-1874.

    View full details


All Publications

  • Impact of 5-HTTLPR on hippocampal subregional activation in older adults TRANSLATIONAL PSYCHIATRY Garrett, A., Gupta, S., Reiss, A. L., Waring, J., Sudheimer, K., Anker, L., Sosa, N., Hallmayer, J. F., O'Hara, R. 2015; 5
  • Using neuroimaging to evaluate and guide pharmacological and psychotherapeutic treatments for mood disorders in children CNS SPECTRUMS Singh, M. K., Garrett, A. S., Chang, K. D. 2015; 20 (4): 359-368


    Mood disorders are increasing in childhood, and often require multimodal and comprehensive treatment plans to address a complex array of symptoms and associated morbidities. Pharmacotherapy, in combination with psychotherapeutic interventions, is essential for treatment and stabilization. Current evidence supports the use of a number of interventions in children and adolescents diagnosed with DSM-5 mood spectrum disorders, which are associated with impairments in prefrontal-striatal-limbic networks, which are key for emotional functioning and regulation. Yet, little is known about the neurobiological effects of interventions on the developing brain. This chapter provides a synopsis of the literature demonstrating the neural effects of psychotropic medications and psychotherapy in youth with depressive or bipolar spectrum disorders. Additional longitudinal and biological studies are warranted to characterize the effects of these interventions on all phases and stages of mood illness development in children and adolescents.

    View details for DOI 10.1017/S1092852914000819

    View details for Web of Science ID 000359008300005

    View details for PubMedID 25659836

  • Decreased Hypothalamic Functional Connectivity with Subgenual Cortex in Psychotic Major Depression NEUROPSYCHOPHARMACOLOGY Sudheimer, K., Keller, J., Gomez, R., Tennakoon, L., Reiss, A., Garrett, A., Kenna, H., O'Hara, R., Schatzberg, A. F. 2015; 40 (4): 849-860


    Hypothalamus communication with the rest of the brain and peripheral target tissues is critically important for many physiological and psychological functions. These functions include maintaining neuroendocrine circadian rhythms and managing affective processes. The hypothalamus maintains both direct neural connections within the brain and it also controls a variety of neuroendocrine processes that can influence target tissues throughout the body. Dysregulation of the hypothalamic pituitary adrenal axis and hyperactivity of the subgenual cortex are both frequently observed in depression. However, many details of how the hypothalamus, the hypothalamic pituitary adrenal (HPA) axis, and the subgenual cingulate interact with each other are unknown. We hypothesized that resting-state functional connectivity between the hypothalamus and the subgenual cortex would be associated with altered circadian rhythm in patients with depression and depressive symptoms. We also hypothesized that this would be most apparent in patients that have major depression with psychotic symptoms, who typically have the most robust HPA-axis dysregulation. Resting-state functional magnetic resonance imaging (fMRI) scans were collected to observe low-frequency resting-state functional connectivity patterns of the hypothalamus in 39 healthy participants, 39 patients with major depression, and 22 patients with major depression with psychotic symptoms. Hourly overnight measures of cortisol secretion and multiple measures of psychiatric symptom severity were also collected on all. Strong hypothalamic functional connectivity with the subgenual cortex was observed in healthy participants. This connectivity was significantly reduced in patients with psychotic major depression. Increased cortisol secretion during the circadian nadir and reduced connectivity were both associated with symptom severity. Reduced connectivity and high cortisol secretion during the circadian nadir are both useful for explaining a significant amount of variance in symptom severity that occurs between healthy participants and depressed patients. However, only cortisol secretion was useful for explaining the severity of symptoms within the depressed groups. This study suggests that the communication between the hypothalamus and the subgenual cortex is disrupted in patients with major depression with psychotic features. It also suggests that these disruptions are associated with increased symptom severity and may be a cause or a consequence of cortisol dysregulation.

    View details for DOI 10.1038/npp.2014.259

    View details for Web of Science ID 000349509000007

  • Changes in brain activation following psychotherapy for youth with mood dysregulation at familial risk for bipolar disorder PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Garrett, A. S., Miklowitz, D. J., Howe, M. E., Singh, M. K., Acquaye, T. K., Hawkey, C. G., Glover, G. H., Reiss, A. L., Chang, K. D. 2015; 56: 215-220
  • Predicting clinical outcome using brain activation associated with set-shifting and central coherence skills in Anorexia Nervosa JOURNAL OF PSYCHIATRIC RESEARCH Garrett, A. S., Lock, J., Datta, N., Beenhaker, J., Kesler, S. R., Reiss, A. L. 2014; 57: 26-33


    Patients with Anorexia Nervosa (AN) have neuropsychological deficits in Set-Shifting (SS) and central coherence (CC) consistent with an inflexible thinking style and overly detailed processing style, respectively. This study investigates brain activation during SS and CC tasks in patients with AN and tests whether this activation is a biomarker that predicts response to treatment.FMRI data were collected from 21 females with AN while performing an SS task (the Wisconsin Card Sort) and a CC task (embedded figures), and used to predict outcome following 16 weeks of treatment (either 16 weeks of cognitive behavioral therapy or 8 weeks cognitive remediation therapy followed by 8 weeks of cognitive behavioral therapy).Significant activation during the SS task included bilateral dorsolateral and ventrolateral prefrontal cortex and left anterior middle frontal gyrus. Higher scores on the neuropsychological test of SS (measured outside the scanner at baseline) were correlated with greater DLPFC and VLPFC/insula activation. Improvements in SS following treatment were significantly predicted by a combination of low VLPFC/insula and high anterior middle frontal activation (R squared = .68, p = .001). For the CC task, visual and parietal cortical areas were activated, but were not significantly correlated with neuropsychological measures of CC and did not predict outcome.Cognitive flexibility requires the support of several prefrontal cortex resources. As previous studies suggest that the VLPFC is important for selecting context-appropriate responses, patients who have difficulties with this skill may benefit the most from cognitive therapy with or without cognitive remediation therapy. The ability to sustain inhibition of an unwanted response, subserved by the anterior middle frontal gyrus, is a cognitive feature that predicts favorable outcome to cognitive treatment. CC deficits may not be an effective predictor of clinical outcome.

    View details for DOI 10.1016/j.jpsychires.2014.06.013

    View details for Web of Science ID 000341550100003

    View details for PubMedID 25027478

  • Aberrant Face and Gaze Habituation in Fragile X Syndrome AMERICAN JOURNAL OF PSYCHIATRY Bruno, J. L., Garrett, A. S., Quintin, E., Mazaika, P. K., Reiss, A. L. 2014; 171 (10): 1099-1106
  • Neurobiological Clues of Risk for Bipolar Disorder Development PSYCHIATRIC ANNALS Chang, K. D., Garrett, A., Singh, M. 2014; 44 (10): 466-470
  • Deformations of amygdala morphology in familial pediatric bipolar disorder. Bipolar disorders Kelley, R., Chang, K. D., Garrett, A., Alegría, D., Thompson, P., Howe, M., L Reiss, A. 2013; 15 (7): 795-802


    Smaller amygdalar volumes have been consistently observed in pediatric bipolar disorder subjects compared to healthy control subjects. Whether smaller amygdalar volume is a consequence or antecedent of the first episode of mania is not known. Additionally, smaller volume has not been localized to specific amygdala subregions.We compared surface contour maps of the amygdala between 22 youths at high risk for bipolar disorder, 26 youths meeting full diagnostic criteria for pediatric familial bipolar disorder, and 24 healthy control subjects matched for age, gender, and intelligence quotient. Amygdalae were manually delineated on three-dimensional spoiled gradient echo images by a blinded rater using established tracing protocols. Statistical surface mesh modeling algorithms supported by permutation statistics were used to identify regional surface differences between the groups.When compared to high-risk subjects and controls, youth with bipolar disorder showed surface deformations in specific amygdalar subregions, suggesting smaller volume of the basolateral nuclei. The high-risk subjects did not differ from controls in any subregion.These findings support previous reports of smaller amygdala volume in pediatric bipolar disorder and map the location of abnormality to specific amygdala subregions. These subregions have been associated with fear conditioning and emotion-enhanced memory. The absence of amygdala size abnormalities in youth at high risk for bipolar disorder suggests that reductions might occur after the onset of mania.

    View details for DOI 10.1111/bdi.12114

    View details for PubMedID 24034354

  • Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression PSYCHIATRY RESEARCH-NEUROIMAGING Kelley, R., Garrett, A., Cohen, J., Gomez, R., Lembke, A., Keller, J., Reiss, A. L., Schatzberg, A. 2013; 211 (2): 119-126
  • Volumetric reductions in the subgenual anterior cingulate cortex in adolescents with bipolar I disorder BIPOLAR DISORDERS Singh, M. K., Chang, K. D., Chen, M. C., Kelley, R. G., Garrett, A., Mitsunaga, M. M., Bararpour, L., Howe, M., Reiss, A. L., Gotlib, I. H. 2012; 14 (6): 585-596


    A range of prefrontal and subcortical volumetric abnormalities have been found in adults and adolescents with bipolar disorder. It is unclear, however, if these deficits are present early in the onset of mania or are a consequence of multiple mood episodes or prolonged exposure to medication. The goal of this study was to examine whether youth with bipolar I disorder who recently experienced their first episode of mania are characterized by brain volumetric abnormalities.Anatomical images from magnetic resonance imaging of 26 13- to 18-year-old adolescents with bipolar I disorder and 24 age-comparable healthy controls with no personal or family history of psychopathology were analyzed using whole-brain voxel-based morphometry (VBM).Compared with healthy controls, adolescents with bipolar I disorder had significantly less gray matter volume in the left subgenual cingulate cortex [p<0.05, family-wise error (FWE)-corrected].Adolescents with a recent single episode of mania have smaller subgenual cingulate cortex volume than do their healthy counterparts, suggesting that this anomaly occurs early in the onset of, or may predate the disorder. Longitudinal studies are needed to examine the impact of this volumetric reduction on the course and outcome of this disorder.

    View details for DOI 10.1111/j.1399-5618.2012.01043.x

    View details for Web of Science ID 000308286800002

    View details for PubMedID 22938166

  • Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Garrett, A. S., Reiss, A. L., Howe, M. E., Kelley, R. G., Singh, M. K., Adleman, N. E., Karchemskiy, A., Chang, K. D. 2012; 51 (8): 821-831


    Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late phase of activation, suggesting different temporal characteristics of brain responses.A total of 20 euthymic adolescents with familial BD (14 male) and 21 healthy control subjects (13 male) underwent fMRI scanning during presentation of happy, sad, and neutral facial expressions. Whole-brain voxelwise analyses were conducted in SPM5, using a three-way analysis of variance (ANOVA) with factors group (BD and healthy control [HC]), facial expression (happy, sad, and neutral versus scrambled), and phase (early and late, corresponding to the first and second half of each block of faces).There were no significant group differences in task performance, age, gender, or IQ. Significant activation from the main effect of group included greater DLPFC activation in the HC group, and greater amygdala/hippocampal activation in the BD group. The interaction of Group × Phase identified clusters in the superior temporal sulcus/insula and visual cortex, where activation increased from the early to late phase of the block for the BD but not the HC group.These findings are consistent with previous studies that suggest deficient prefrontal cortex regulation of heightened amygdala response to emotional stimuli in pediatric BD. Increasing activation over time in superior temporal and visual cortices suggests difficulty processing or disengaging attention from emotional faces in BD.

    View details for DOI 10.1016/j.jaac.2012.06.005

    View details for Web of Science ID 000307128300010

    View details for PubMedID 22840553

  • Neurometabolite Effects of Response to Quetiapine and Placebo in Adolescents with Bipolar Depression JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Chang, K., DelBello, M., Chu, W., Garrett, A., Kelley, R., Mills, N., Howe, M., Bryan, H., Adler, C., Eliassen, J., Spielman, D., Strakowski, S. M. 2012; 22 (4): 261-268


    Mood stabilizers have been reported to affect brain concentrations of myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and potential predictors of response to QUET in adolescents with bipolar depression.Twenty-six adolescents with bipolar depression participated in an 8-week placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and 4T at two sites, with 8?cm(3) voxels placed in the right and left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used to calculate absolute concentrations of NAA and mI.Twenty-six subjects had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS] score). Although baseline ACC mI did not predict responder status, responders had significantly lower posttreatment ACC mI values than did nonresponders (3.27±.71 vs. 4.23±.70; p=0.004). There were no significant differences in the changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group (ACC: -0.55±1.3 vs.+0.25±1.5, p=0.23; right-DLPFC: -0.55±1.3 vs. 0.33±0.89, p=0.13; left-DLPFC: -0.04±0.91 vs.+0.29±0.61, p=0.41).We found that posttreatment, not baseline, ACC mI levels were associated with response to QUET in adolescents with bipolar depression. There were no differences in NAA concentration changes between the QUET and PBO groups. Larger studies including different brain regions would help to clarify the effects of QUET on neurochemistry in patients with bipolar disorder.

    View details for DOI 10.1089/cap.2011.0153

    View details for Web of Science ID 000307933800002

    View details for PubMedID 22849427

  • Effects of medication on neuroimaging findings in bipolar disorder: an updated review BIPOLAR DISORDERS Hafeman, D. M., Chang, K. D., Garrett, A. S., Sanders, E. M., Phillips, M. L. 2012; 14 (4): 375-410


    Neuroimaging is an important tool for better understanding the neurobiological underpinnings of bipolar disorder (BD). However, potential study participants are often receiving psychotropic medications which can possibly confound imaging data. To better interpret the results of neuroimaging studies in BD, it is important to understand the impact of medications on structural magnetic resonance imaging (sMRI), functional MRI (fMRI), and diffusion tensor imaging (DTI).To better understand the impact of medications on imaging data, we conducted a literature review and searched MEDLINE for papers that included the key words bipolar disorder and fMRI, sMRI, or DTI. The search was limited to papers that assessed medication effects and had not been included in a previous review by Phillips et al. (Medication effects in neuroimaging studies of bipolar disorder. Am J Psychiatry 2008; 165: 313-320). This search yielded 74 sMRI studies, 46 fMRI studies, and 15 DTI studies.Medication appeared to influence many sMRI studies, but had limited impact on fMRI and DTI findings. From the structural studies, the most robust finding (20/45 studies) was that lithium was associated with increased volumes in areas important for mood regulation, while antipsychotic agents and anticonvulsants were generally not. Regarding secondary analysis of the medication effects of fMRI and DTI studies, few showed significant effects of medication, although rigorous analyses were typically not possible when the majority of subjects were medicated. Medication effects were more frequently observed in longitudinal studies designed to assess the impact of particular medications on the blood oxygen level-dependent (BOLD) signal. With a few exceptions, the observed effects were normalizing, meaning that the medicated individuals with BD were more similar than their unmedicated counterparts to healthy subjects.The effects of psychotropic medications, when present, are predominantly normalizing and thus do not seem to provide an alternative explanation for differences in volume, white matter tracts, or BOLD signal between BD participants and healthy subjects. However, the normalizing effects of medication could obfuscate differences between BD and healthy subjects, and thus might lead to type II errors.

    View details for DOI 10.1111/j.1399-5618.2012.01023.x

    View details for Web of Science ID 000304441200005

    View details for PubMedID 22631621

  • BRAIN ACTIVATION TO FACIAL EXPRESSIONS IN YOUTH WITH PTSD SYMPTOMS DEPRESSION AND ANXIETY Garrett, A. S., Carrion, V., Kletter, H., Karchemskiy, A., Weems, C. F., Reiss, A. 2012; 29 (5): 449-459


    This study examined activation to facial expressions in youth with a history of interpersonal trauma and current posttraumatic stress symptoms (PTSS) compared to healthy controls (HC).Twenty-three medication-naive youth with PTSS and 23 age- and gender-matched HC underwent functional magnetic resonance imaging (fMRI) while viewing fearful, angry, sad, happy, and neutral faces. Data were analyzed for group differences in location of activation, as well as timing of activation during the early versus late phase of the block. Using SPM5, significant activation (P < .05 FWE [Family-Wise Error] corrected, extent = 10 voxels) associated with the main effect of group was identified. Activation from selected clusters was extracted to SPSS software for further analysis of specific facial expressions and temporal patterns of activation.The PTSS group showed significantly greater activation than controls in several regions, including the amygdala/hippocampus, medial prefrontal cortex, insula, and ventrolateral prefrontal cortex, and less activation than controls in the dorsolateral prefrontal cortex (DLPFC). These group differences in activation were greatest during angry, happy, and neutral faces, and predominantly during the early phase of the block. Post hoc analyses showed significant Group × Phase interactions in the right amygdala and left hippocampus.Traumatic stress may impact development of brain regions important for emotion processing. Timing of activation may be altered in youth with PTSS.

    View details for DOI 10.1002/da.21892

    View details for Web of Science ID 000303440700010

    View details for PubMedID 22553009

  • Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder PSYCHIATRY RESEARCH-NEUROIMAGING Karchemskiy, A., Garrett, A., Howe, M., Adleman, N., Simeonova, D. I., Alegria, D., Reiss, A., Chang, K. 2011; 194 (3): 319-325


    Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD.

    View details for DOI 10.1016/j.pscychresns.2011.03.006

    View details for Web of Science ID 000298522600016

    View details for PubMedID 22041532

  • Striatal volumes in pediatric bipolar patients with and without comorbid ADHD PSYCHIATRY RESEARCH-NEUROIMAGING Liu, I. Y., Howe, M., Garrett, A., Karchemskiy, A., Kelley, R., Alegria, D., Reiss, A., Chang, K. 2011; 194 (1): 14-20


    The most prevalent comorbid disorder in pediatric bipolar disorder (BD) is attention-deficit/hyperactivity disorder (ADHD). As caudate volume abnormalities have been demonstrated in both BD and ADHD, this study sought to determine whether these findings could be attributed to separable effects from either diagnosis. High resolution anatomical magnetic resonance (MRI) images were obtained from youth in 4 groups: BD with comorbid ADHD (n=17), BD without comorbid ADHD (n=12), youth with ADHD alone (n=11), and healthy control subjects (n=24). Caudate, putamen, and globus pallidus volumes were manually traced for each subject using BrainImageJava software by a reliable rater blinded to diagnosis. There was a significant effect of diagnosis on striatal volumes, with ADHD associated with decreased caudate and putamen volumes, and BD associated with increased caudate, putamen, and globus pallidus volumes. Thus, the presence or absence of comorbid ADHD in patients with BD was associated with distinct alterations in caudate volumes, suggesting that these groups have different, but related, mechanisms of neuropathology.

    View details for DOI 10.1016/j.pscychresns.2011.06.008

    View details for Web of Science ID 000296544300003

    View details for PubMedID 21875781

  • Increased Subgenual Cingulate Cortex Volume in Pediatric Bipolar Disorder Associated with Mood Stabilizer Exposure JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Mitsunaga, M. M., Garrett, A., Howe, M., Karchemskiy, A., Reiss, A., Chang, K. 2011; 21 (2): 149-155


    The subgenual cingulate (SGC) cortex has been implicated in the pathophysiology of mood disorders. We sought to study morphometric characteristics of the SGC in pediatric subjects with familial bipolar disorder (BD) compared with healthy controls.Twenty children and adolescents with BD (mean age?=?14.6 years, 4 females) and 20 healthy age-, gender-, and intelligence quotient-matched controls underwent high-resolution anatomical magnetic resonance imaging. Patients were primarily euthymic and most were taking medications. SGC cortex volumes were determined by manual tracings from a reliable rater, blinded to diagnosis. Analyses of covariance were performed with total cerebral gray matter and age as covariates.No differences were found in SGC volumes between BD subjects and healthy controls. Further analysis revealed that BD subjects with past mood stabilizer exposure had significantly increased SGC volumes compared with BD subjects without mood stabilizer exposure, and compared with controls. The increase was driven by larger bilateral posterior SGC volumes.Youth with familial BD do not appear to have abnormalities in SGC volume. Mood stabilizer exposure, however, may be correlated with increases in SGC volume.

    View details for DOI 10.1089/cap.2010.0094

    View details for Web of Science ID 000289678800006

    View details for PubMedID 21486168

  • Aberrant Brain Activation During a Working Memory Task in Psychotic Major Depression AMERICAN JOURNAL OF PSYCHIATRY Garrett, A., Kelly, R., Gomez, R., Keller, J., Schatzberg, A. F., Reiss, A. L. 2011; 168 (2): 173-182


    The authors sought to better understand the neural circuitry associated with working memory deficits in psychotic major depression by examining brain function during an N-back task.Study subjects were 16 patients with psychotic major depression, 15 patients with nonpsychotic major depression, and 19 healthy comparison subjects. Functional MRI data were collected while participants responded to letter stimuli that were repeated from the previous trial (1-back) or the one before that (2-back).Relative to the healthy comparison group, both the psychotic and nonpsychotic major depression groups had significantly greater activation in the right parahippocampal gyrus during the 2-back task, and the psychotic major depression group showed this overactivation during the 1-back task as well. The nonpsychotic major depression group showed significantly lower activation than other groups in the right dorsolateral prefrontal cortex and greater activation than the healthy comparison group in the superior occipital cortex. The psychotic major depression group was unique in showing greater activation than both other groups in the right temporoparietal junction, a cluster that also demonstrated connectivity with activation in the left prefrontal cortex.The psychotic major depression group showed aberrant parahippocampal activation at a lower demand level than observed in nonpsychotic major depression. While the nonpsychotic major depression group showed abnormalities in frontal executive regions, the psychotic major depression group showed abnormalities in temporoparietal regions associated with orienting to unexpected stimuli. Considering the functional connectivity of this cluster with left dorsolateral prefrontal cortex regions, these findings may reflect neural compensation for sensory gating deficits in psychotic major depression.

    View details for DOI 10.1176/appi.ajp.2010.09121718

    View details for Web of Science ID 000286972800011

    View details for PubMedID 21078708

  • Aberrant Brain Activation During a Response Inhibition Task in Adolescent Eating Disorder Subtypes AMERICAN JOURNAL OF PSYCHIATRY Lock, J., Garrett, A., Beenhakker, J., Reiss, A. L. 2011; 168 (1): 55-64


    Behavioral and personality characteristics associated with excessive inhibition and disinhibition are observed in patients with eating disorders, but neural correlates of inhibitory control have not been examined in adolescents with these disorders.Thirteen female adolescents with binge eating and purging behaviors (i.e., bulimia nervosa or anorexia nervosa, binge eating/purging type);14 with anorexia nervosa, restricting type; and 13 healthy comparison subjects performed a rapid, jittered event-related go/no-go task. Functional magnetic resonance images were collected using a 3 Tesla GE scanner and a spiral pulse sequence. A whole-brain three-group analysis of variance in SPM5 was used to identify significant activation associated with the main effect of group for the comparison of correct no-go versus go trials. The mean activation in these clusters was extracted for further comparisons in SPSS.The binge eating/purging group showed significantly greater activation than the healthy comparison group in the bilateral precentral gyri, anterior cingulate cortex, and middle and superior temporal gyri as well as greater activation relative to both comparison and restricting type anorexia subjects in the hypothalamus and right dorsolateral prefrontal cortex. Within-group analysis found that only the restricting type anorexia group showed a positive correlation between the percent correct on no-go trials and activation in posterior visual and inferior parietal cortex regions.The present study provides preliminary evidence that during adolescence, eating disorder subtypes may be distinguishable in terms of neural correlates of inhibitory control. This distinction is consistent with differences in behavioral impulsivity in these patient groups.

    View details for DOI 10.1176/appi.ajp.2010.10010056

    View details for Web of Science ID 000285868100010

    View details for PubMedID 21123315

  • Reduced Hippocampal Activity in Youth with Posttraumatic Stress Symptoms: An fMRI Study JOURNAL OF PEDIATRIC PSYCHOLOGY Carrion, V. G., Haas, B. W., Garrett, A., Song, S., Reiss, A. L. 2010; 35 (5): 559-569


    Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) develop cognitive deficits that impact their development. Our goal is to investigate the function of the hippocampus in adolescents with PTSS during a memory processing task.Twenty-seven adolescents between the ages of 10-17 years (16 with PTSS and 11 healthy controls) encoded and retrieved visually presented nouns (Verbal Declarative Memory Task) while undergoing fMRI scanning.The PTSS group demonstrated reduced activation of the right hippocampus during the retrieval component of the task. Further, severity of symptoms of avoidance and numbing correlated with reduced left hippocampal activation during retrieval.Decreased activity of the hippocampus during a verbal memory task may be a neurofunctional marker of PTSS in youth with history of interpersonal trauma. The results of this study may facilitate the development of focused treatments and may be of utility when assessing treatment outcome for PTSS.

    View details for DOI 10.1093/jpepsy/jsp112

    View details for Web of Science ID 000278614700012

    View details for PubMedID 19995868

  • Neural Correlates of Response Inhibition in Pediatric Bipolar Disorder JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Singh, M. K., Chang, K. D., Mazaika, P., Garrett, A., Adleman, N., Kelley, R., Howe, M., Reiss, A. 2010; 20 (1): 15-24


    Pediatric bipolar disorder is characterized by core deficits in mood and executive function and commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD). We aimed to examine response inhibition in this population, as an element of executive function, which, if aberrant, may interfere with learning and information processing.Children (9-18 years) with bipolar I or II disorder (BD, n = 26) and age, gender, and intelligence quotient (IQ) comparable healthy children (HC, n = 22) without any psychopathology were given a standardized Go/NoGo computerized task measuring response inhibition. A whole-brain functional magnetic resonance imaging (MRI) group analysis was performed using statistical parametric mapping software (SPM2) for comparing NoGo to Go epochs.There were no statistically significant group differences between groups in age, gender, or ethnicity. The BD group had high rates of co-morbid disorders, including 81% with ADHD, 62% with oppositional defiant disorder (ODD), and 46% with anxiety disorders. This BD group had fewer correct responses on Go (84% vs. 96%, T[46] = 3.35, p = 0.002) and overall (85% vs. 94%, T[46] = 4.12, p = 0.0002) trials as compared to the HC group. However, there were no statistically significant group differences in response inhibition on NoGo trials (p = 0.11). In the NoGo-Go contrast, the BD group showed increased neural activation in the right dorsolateral prefrontal cortex (DLPFC) compared to HC (T[46] = 4.21, p < 0.001).During accurate NoGo but impaired Go trial performance, children with BD showed increased right DLPFC activation versus controls, suggesting increased recruitment of executive control regions for accurate response inhibition. Studies relating these results to mood regulation in pediatric BD are warranted.

    View details for DOI 10.1089/cap.2009.0004

    View details for Web of Science ID 000274636300003

    View details for PubMedID 20166792

  • Effect of Divalproex on Brain Morphometry, Chemistry, and Function in Youth at High-Risk for Bipolar Disorder: A Pilot Study JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Chang, K., Karchemskiy, A., Kelley, R., Howe, M., Garrett, A., Adleman, N., Reiss, A. 2009; 19 (1): 51-59


    Divalproex has been found efficacious in treating adolescents with and at high risk for bipolar disorder (BD), but little is known about the effects of mood stabilizers on the brain itself. We sought to examine the effects of divalproex on the structure, chemistry, and function of specific brain regions in children at high-risk for BD.A total of 24 children with mood dysregulation but not full BD, all offspring of a parent with BD, were treated with divalproex monotherapy for 12 weeks. A subset of 11 subjects and 6 healthy controls were scanned with magnetic resonance imaging (MRI, magnetic resonance spectroscopy [MRS], and functional MRI [fMRI]) at baseline and after 12 weeks.There were no significant changes in amygdalar or cortical volume found over 12 weeks. Furthermore, no changes in neurometabolite ratios were found. However, we found the degree of decrease in prefrontal brain activation to correlate with degree of decrease in depressive symptom severity.Bipolar offspring at high risk for BD did not show gross morphometric, neurometabolite, or functional changes after 12 weeks of treatment with divalproex. Potential reasons include small sample size, short exposure to medications, or lack of significant neurobiological impact of divalproex in this particular population.

    View details for DOI 10.1089/cap.2008.060

    View details for Web of Science ID 000263913500007

    View details for PubMedID 19232023

  • WOMEN WITH HYPOACTIVE SEXUAL DESIRE DISORDER COMPARED TO NORMAL FEMALES: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY NEUROSCIENCE Arnow, B. A., Millheiser, L., Garrett, A., Polan, M. L., Glover, G. H., Hill, K. R., Lightbody, A., Watson, C., Banner, L., Smart, T., Buchanan, T., Desmond, J. E. 2009; 158 (2): 484-502


    Lack of sexual interest is the most common sexual complaint among women. However, factors affecting sexual desire in women have rarely been studied. While the role of the brain in integrating the sensory, attentional, motivational, and motor aspects of sexual response is commonly acknowledged as important, little is known about specific patterns of brain activation and sexual interest or response, particularly among women. We compared 20 females with no history of sexual dysfunction (NHSD) to 16 women with hypoactive sexual desire disorder (HSDD) in a functional magnetic resonance imaging (fMRI) study that included assessment of subjective sexual arousal, peripheral sexual response using a vaginal photoplethysmograph (VPP), as well as brain activation across three time points. Video stimuli included erotic, sports, and relaxing segments. Subjective arousal to erotic stimuli was significantly greater in NHSD participants compared with HSDD. In the erotic-sports contrast, NHSD women showed significantly greater activation in the bilateral entorhinal cortex than HSDD women. In the same contrast, HSDD females demonstrated higher activation than NHSD females in the medial frontal gyrus (Brodmann area (BA) 10), right inferior frontal gyrus (BA 47) and bilateral putamen. There were no between group differences in VPP-correlated brain activation and peripheral sexual response was not significantly associated with either subjective sexual response or brain activation patterns. Findings were consistent across the three experimental sessions. The results suggest differences between women with NHSD and HSDD in encoding arousing stimuli, retrieval of past erotic experiences, or both. The findings of greater activation in BA 10 and BA 47 among women with HSDD suggest that this group allocated significantly more attention to monitoring and/or evaluating their responses than NHSD participants, which may interfere with normal sexual response.

    View details for DOI 10.1016/j.neuroscience.2008.09.044

    View details for Web of Science ID 000262959900012

    View details for PubMedID 18976696

  • Neuroanatomical Abnormalities in Adolescents With Attention-Deficit/Hyperactivity Disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Garrett, A., Penniman, L., Epstein, J. N., Casey, B. J., Hinshaw, S. P., Glover, G., Tonev, S., Vitolo, A., Davidson, M., Spicer, J., Greenhill, L. L., Reiss, A. L. 2008; 47 (11): 1321-1328


    Several neuroanatomic abnormalities have been reported in patients with attention-deficit/hyperactivity disorder (ADHD). However, findings are not always consistent, perhaps because of heterogeneous subject samples. Studying youths with documented familial ADHD provides an opportunity to examine a more homogeneous population.Twenty-four youths with a confirmed history of familial ADHD and 10 control youths underwent high-resolution structural magnetic resonance imaging examinations. Archived magnetic resonance imaging scan data from 12 control youths were included in the analysis to increase statistical power. Individually drawn region-of-interest methods were used to examine the frontal lobe gyri and caudate.Cerebral total tissue was similar between groups. The volumes of the right caudate and right inferior frontal lobe were larger in the ADHD youths compared with the control youths. Data from a subgroup of the ADHD youths suggest that increasing left caudate volume is associated with decreasing functional activation of this region.Because previous studies have focused primarily on younger subjects or used an extended age range, the present results may reflect neurodevelopmental changes specific to late adolescence in familial ADHD.

    View details for DOI 10.1097/CHI.0b013e318185d285

    View details for Web of Science ID 000260444800012

    View details for PubMedID 18827721

  • Aberrant Brain Activation During Gaze Processing in Boys With Fragile X Syndrome ARCHIVES OF GENERAL PSYCHIATRY Watson, C., Hoeft, F., Garrett, A. S., Hall, S. S., Reiss, A. L. 2008; 65 (11): 1315-1323


    Eye contact is a fundamental component of human social behavior. Individuals with fragile X syndrome (fraX), particularly male subjects, avoid eye contact and display other social deficits. To date (to our knowledge), this behavior in fraX has been studied only in female subjects, who show lesser degrees of gaze aversion.To determine the neural correlates of the perception of direct eye gaze in adolescent boys with fraX using functional magnetic resonance imaging.Cross-sectional study.Academic medical center.Thirteen adolescent boys with fraX, 10 boys with developmental delay, and 13 typically developing control subjects.Behavioral performance and brain activation during functional magnetic resonance imaging were evaluated during the presentation of faces with eye gaze directed to or averted away from subjects and during successive presentations of stimuli with eye gaze directed toward the subject. Whole-brain and region of interest analyses and regression analyses with task performance were performed.Significantly greater activation was observed in prefrontal cortices in controls compared with boys having fraX, who (in contrast) demonstrated elevated left insula activation to direct eye gaze stimuli. Furthermore, compared with controls, boys with fraX showed greater sensitization in the left amygdala with successive exposure to direct gaze.Compared with controls, boys with fraX display distinct patterns of brain activation in response to direct eye gaze. These results suggest that aberrant neural processing of direct eye gaze in subjects with fraX may be related to the associated avoidant response.

    View details for Web of Science ID 000260600300009

    View details for PubMedID 18981343

  • The role of the amygdala in bipolar disorder development DEVELOPMENT AND PSYCHOPATHOLOGY Garrett, A., Chang, K. 2008; 20 (4): 1285-1296


    The amygdala has received great interest as a possible neurophysiological substrate of bipolar disorder (BD). This review summarizes information about the structure and function of the amygdala with attention to its role in experienced emotion and mood. We review the evidence for amygdala pathology in psychiatric conditions and discuss the role of the amygdala in BD during development. There appear to be consistent findings in the neuroimaging literature that suggest an etiological model for BD that involves abnormalities in the structure and function of the amygdala, but also depends on the failure of prefrontal cortical regions to modulate amygdala activity. In addition, evidence is accumulating to suggest that this model has flexible outcomes, depending on factors intrinsic and extrinsic to BD, and may follow several possible paths across the course of maturational development.

    View details for DOI 10.1017/S0954579408000618

    View details for Web of Science ID 000260993800014

    View details for PubMedID 18838042

  • Hippocampal and amygdalar volumes in psychotic and nonpsychotic unipolar depression AMERICAN JOURNAL OF PSYCHIATRY Keller, J., Shen, L., Gomez, R. G., Garrett, A., Solvason, H. B., Reiss, A., Schatzberg, A. F. 2008; 165 (7): 872-880


    The limbic system is thought to underlie dysfunctional affective and cognitive processes in individuals with depression. Neuroanatomical studies of subjects with depression have often examined hippocampal and amygdalar structures, since they are two key structures of the limbic system. Research has often but not always found reduced hippocampal volume in patients with major depression. The purpose of the present study was to examine differences in hippocampal and amygdalar volumes in patients with depression subtypes relative to healthy comparison subjects.Participants were 1) patients with major depression with psychosis, 2) patients with major depression without psychosis, and 3) healthy comparison subjects. To examine hippocampal and amygdalar volumes, all participants underwent structural magnetic resonance imaging (MRI). The authors further examined the effects of clinical and chronicity data on these two brain structures.After age, gender, and total brain volume were controlled, depressed patients with psychosis had a significantly smaller mean amygdala volume relative to depressed patients without psychosis and healthy comparison subjects. There were no differences between depressed patients without psychosis and healthy comparison subjects. Correlational analyses suggested that age of depression onset was strongly associated with amygdala volume. No group differences in hippocampal volume were found.There were no differences between depressed patients and healthy comparison subjects in hippocampal volume. However, psychotic but not nonpsychotic depression was associated with reduced amygdala volume. Reduced amygdala volume was not associated with severity of depression or severity of psychosis but was associated with age at onset of depression. Smaller amygdala volume may be a risk factor for later development of psychotic depression. In addition, chronicity of depression and depression subtype might be two important factors associated with hippocampal and amygdalar volumes in depression.

    View details for DOI 10.1176/appi.ajp.2008.07081257

    View details for Web of Science ID 000257320100016

    View details for PubMedID 18450931

  • A preliminary functional magnetic resonance imaging study of prefrontal-amygdalar activation changes in adolescents with bipolar depression treated with lamotrigine BIPOLAR DISORDERS Chang, K. D., Wagner, C., Garrett, A., Howe, M., Reiss, A. 2008; 10 (3): 426-431


    Hypotheses regarding mood dysregulation in bipolar disorder (BD) have centered on limbic overactivity with relative prefrontal underactivity during mood episodes. Therefore, we hypothesized that adolescents with bipolar depression successfully treated with lamotrigine would show decreases in amygdalar activation, and increases in prefrontal activation.Eight adolescents with BD underwent functional magnetic resonance imaging (fMRI) at baseline and after eight weeks of lamotrigine treatment. Blocks of negatively and neutrally valenced emotional pictures were presented during scanning, and subjects were asked to rate how each picture made them feel. Activation in bilateral amygdalae and dorsolateral prefrontal cortices (DLPFC) for negative minus neutral pictures was correlated with Children's Depression Rating Scale (CDRS) scores.Mean (SD) CDRS scores decreased significantly, from 53.0 (10.6) at baseline to 26.3 (5.3) at Week 8. This clinical improvement was correlated with decreased right amygdalar activation (r = 0.91, p = 0.002). At Week 8, but not baseline, CDRS score was positively correlated with bilateral amygdalar activation (r = 0.85, p = 0.007). DLPFC activation was not correlated with change in CDRS score.These preliminary results indicate that adolescents with BD treated with lamotrigine demonstrated less amygdalar activation when viewing negative stimuli as depressive symptoms improved. Larger controlled studies are needed to confirm these findings.

    View details for Web of Science ID 000254807600008

    View details for PubMedID 18402630

  • Posttraumatic stress symptoms and brain function during a response-inhibition task: An fMRI study in youth DEPRESSION AND ANXIETY Carrion, V. G., Garrett, A., Menon, V., Weems, C. F., Reiss, A. L. 2008; 25 (6): 514-526


    Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) can exhibit difficulties in executive function and physiological hyperarousal. Response inhibition has been identified as a core component of executive function. In this study, we investigate the functional neuroanatomical correlates of response inhibition in youth with PTSS. Thirty right-handed medication-naïve youth between the ages of 10 and 16 years underwent a 3-Tesla Functional Magnetic Resonance Imaging scan during a response-inhibition (Go/No-Go) task. Youth with PTSS (n = 16) were age and gender matched to a control group of healthy youth (n = 14). Between-groups analyses were conducted to identify brain regions of greater activation in the No/Go-Go contrasts. PTSS and control youth performed the task with similar accuracy and response times. Control subjects had greater middle frontal cortex activation when compared with PTSS subjects. PTSS subjects had greater medial frontal activation when compared with control subjects. A sub-group of youth with PTSS and a history of self-injurious behaviors demonstrated increased insula and orbitofrontal activation when compared with those PTSS youth with no self-injurious behaviors. Insula activation correlated positively with PTSS severity. Diminished middle frontal activity and enhanced medial frontal activity during response-inhibition tasks may represent underlying neurofunctional markers of PTSS.

    View details for DOI 10.1002/da.20346

    View details for Web of Science ID 000257017000007

    View details for PubMedID 17598145

  • Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD AMERICAN JOURNAL OF PSYCHIATRY Casey, B. J., Epstein, J. N., Buhle, J., Liston, C., Davidson, M. C., Tonev, S. T., Spicer, J., Niogi, S., Millner, A. J., Reiss, A., Garrett, A., Hinshaw, S. P., Greenhill, L. L., Shafritz, K. M., Vitolo, A., Kotler, L. A., Jarrett, M. A., Glover, G. 2007; 164 (11): 1729-1736


    Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder.Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function.Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children.Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder.

    View details for DOI 10.1176/appi.ajp.2007.06101754

    View details for Web of Science ID 000250811200020

    View details for PubMedID 17974939

  • ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY Epstein, J. N., Casey, B. J., Tonev, S. T., Davidson, M. C., Reiss, A. L., Garrett, A., Hinshaw, S. P., Greenhill, L. L., Glover, G., Shafritz, K. M., Vitolo, A., Kotler, L. A., Jarrett, M. A., Spicer, J. 2007; 48 (9): 899-913


    Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication.A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task.Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions.This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.

    View details for DOI 10.1111/j.1469-7610.2007.01761.x

    View details for Web of Science ID 000249130800007

    View details for PubMedID 17714375

  • Assessment and prevention of head motion during imaging of patients with attention deficit hyperactivity disorder PSYCHIATRY RESEARCH-NEUROIMAGING Epstein, J. N., Casey, B. J., Tonev, S. T., Davidson, M., Reiss, A. L., Garrett, A., Hinshaw, S. P., Greenhill, L. L., Vitolo, A., Kotler, L. A., Jarrett, M. A., Spicer, J. 2007; 155 (1): 75-82


    The present study serves to detail the specific procedures for a mock scanner protocol, report on its use in the context of a multi-site study, and make suggestions for improving such protocols based on data acquired during study scanning. Specifically, a mock scanner compliance training protocol was used in a functional imaging study with a group of adolescents and adults with Attention Deficit Hyperactivity Disorder (ADHD) and a matched sample of healthy children and adults. Head motion was measured during mock and actual scanning. Participants across groups exhibited excess motion (>2 mm) on 43% of runs during the mock scanner. During actual scanning, excessive motion was limited to 10% of runs. There was a clear task-correlated head motion during a go/no-go task that occurred even after the compliance training: participants had a tendency to respond with increased head motion immediately after committing an error. This study illustrates the need to (1) report data attrition due to head motion, (2) assess task-related motion, and (3) consider mock scanner training in functional imaging protocols.

    View details for DOI 10.1016/j.pscyhresns.2006.12.009

    View details for Web of Science ID 000246515400008

    View details for PubMedID 17395436

  • Separating subjective emotion from the perception of emotion-inducing stimuli: An fMRI study NEUROIMAGE Garrett, A. S., Maddock, R. J. 2006; 33 (1): 263-274


    fMRI was used to dissociate neural responses temporally associated with the subjective experience of emotion from those associated with the perception of emotion-inducing stimuli in order to better define the emotion-related functions of the amygdala, lateral orbital frontal cortex (OFC), and hippocampus. Subjects viewed aversive pictures followed by an extended post-stimulus period of sustained subjective emotion. Brain regions showing activation paralleling the period of sustained subjective emotion were distinguished from those showing activation limited to the period of aversive picture presentation. Behavioral results showed that subjective ratings of emotion remained elevated for 20 s after offset of the aversive pictures. fMRI results showed that viewing aversive pictures activated the amygdala, lateral OFC, and hippocampus. Subjective emotion (present both during and after aversive pictures) was temporally associated with activation in the right lateral OFC and left hippocampus but not the amygdala. Ratings of subjective emotion were correlated with activation in the right lateral OFC and left hippocampus. The results support direct amygdala involvement in emotion perception but suggest that amygdala activation is not temporally associated with subjective emotion that occurs after the offset of emotion-related stimuli. The results are consistent with a general role for the lateral OFC in monitoring or reflecting on internal experience and show that hippocampal activation is sustained during a period of subjective emotion, possibly related to enhanced memory encoding for the aversive pictures.

    View details for DOI 10.1016/j.neuroimagae.2006.05.024

    View details for Web of Science ID 000241209800027

    View details for PubMedID 16908199

  • Will neuroimaging ever be used to diagnose pediatric bipolar disorder? DEVELOPMENT AND PSYCHOPATHOLOGY Chang, K., Adleman, N., Wagner, C., Barnea-Goraly, N., Garrett, A. 2006; 18 (4): 1133-1146


    There is a great need for discovery of biological markers that could be used diagnostically for pediatric onset disorders, particularly those with potentially confusing phenomenology such as pediatric-onset bipolar disorder (BD). Obtaining these markers would help overcome current subjective diagnostic techniques of relying on parent and child interview and symptomatic history. Brain imaging may be the most logical choice for a diagnostic tool, and certain neurobiological abnormalities have already been found in pediatric BD. However, much work remains to be done before neuroimaging can be used reliably to diagnose this disorder, and because of the nature of BD and the limitations of imaging technology and technique, neuroimaging will likely at most be only a diagnostic aide in the near future. In this paper we discuss the characteristics of pediatric BD that complicate the use of biological markers as diagnostic tools, how neuroimaging techniques have been used to study pediatric BD so far, and the limitations and potential of such techniques for future diagnostic use.

    View details for DOI 10.1017/S0954579406060548

    View details for Web of Science ID 000241933300009

    View details for PubMedID 17064431

  • Reduced amygdalar gray matter volume in familial pediatric bipolar disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Chang, K., Karchemskiy, A., Barnea-Goraly, N., Garrett, A., Simeonova, D. I., Reiss, A. 2005; 44 (6): 565-573


    Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls.Twenty children and adolescents with BD I (mean age = 14.6 years, four females) and 20 healthy age, gender, and IQ-matched controls underwent high-resolution magnetic resonance imaging at 3 T. Patients were mostly euthymic and most were taking medications. Amygdala, hippocampus, thalamus, and caudate volumes were determined by manual tracings from researchers blinded to diagnosis. Analyses of covariance were performed, with total brain volume, age, and gender as covariates.No differences were found in the volumes of hippocampus, caudate, and thalamus between subjects with BD and controls. Subjects with BD had smaller volumes in the left and right amygdala, driven by reductions in gray matter volume. Exploratory analyses revealed that subjects with BD with past lithium or valproate exposure tended to have greater amygdalar gray matter volume than subjects with BD without such exposure.Children and adolescents with early-onset BD may have reduced amygdalar volumes, consistent with other studies in this population. Prolonged medication exposure to lithium or valproate may account for findings in adults with BD of increased amygdalar volume relative to controls.

    View details for DOI 10.1097/01.chi.0000159948.75136.0d

    View details for Web of Science ID 000229245600011

    View details for PubMedID 15908839

  • Anomalous brain activation during face and gaze processing in Williams syndrome NEUROLOGY Mobbs, D., Garrett, A. S., Menon, V., Rose, F. E., Bellugi, U., Reiss, A. L. 2004; 62 (11): 2070-2076


    To investigate the discrete neural systems that underlie relatively preserved face processing skills in Williams syndrome (WS).The authors compared face and eye-gaze direction processing abilities in 11 clinically and genetically diagnosed WS subjects with 11 healthy age- and sex-matched controls, using functional MRI (fMRI).Compared to controls, WS subjects showed a strong trend toward being less accurate in determining the direction of gaze and had significantly longer response latencies. Significant increases in activation were observed in the right fusiform gyrus (FuG) and several frontal and temporal regions for the WS group. By comparison, controls showed activation in the bilateral FuG, occipital, and temporal lobes. Between-group analysis showed WS subjects to have more extensive activation in the right inferior, superior, and medial frontal gyri, anterior cingulate, and several subcortical regions encompassing the anterior thalamus and caudate. Conversely, controls had greater activation in the primary and secondary visual cortices.The observed patterns of activation in WS subjects suggest a preservation of neural functioning within frontal and temporal regions, presumably resulting from task difficulty or compensatory mechanisms. Persons with WS may possess impairments in visual cortical regions, possibly disrupting global-coherence and visuospatial aspects of face and gaze processing.

    View details for Web of Science ID 000221890400030

    View details for PubMedID 15184616

  • Here's looking at you, kid - Neural systems underlying face and gaze processing in fragile X syndrome ARCHIVES OF GENERAL PSYCHIATRY Garrett, A. S., Menon, V., MacKenzie, K., Reiss, A. L. 2004; 61 (3): 281-288


    Children with fragile X syndrome (fraX) are at risk for manifesting abnormalities in social function that overlap with features of autism and social anxiety disorder. In this study, we analyzed brain activation in response to face and gaze stimuli to better understand neural functioning associated with social perception in fraX.Eleven female subjects with fraX, aged 10 to 22 years, were compared with age-matched female control subjects. Photographs of forward-facing and angled faces, each having direct and averted gaze (4 types of stimuli), were presented in an event-related design during functional magnetic resonance imaging. Subjects were instructed to determine the direction of gaze for each photograph. Activation in brain regions known to respond to face and gaze stimuli, the fusiform gyrus (FG) and superior temporal sulcus (STS), were compared between groups to isolate neural abnormalities in the perception of directed social stimuli.The fraX subjects had decreased accuracy in determining the direction of gaze compared with controls. Region of interest analysis of the FG revealed a significant interaction between diagnostic group and face orientation. Specifically, control subjects had greater FG activation to forward than to angled faces, whereas fraX subjects had no difference in FG activation to forward and angled faces. Controls showed greater left STS activation to all stimuli compared with fraX subjects.Our results suggest that gaze aversion in fraX subjects is related to decreased specialization of the FG in the perception of face orientation. Decreased STS activation in fraX suggests aberrant processing of gaze. These data suggest that gaze aversion in fraX may be related to dysfunction of neural systems underlying both face and gaze processing.

    View details for Web of Science ID 000220064800009

    View details for PubMedID 14993116

  • Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy NEUROPSYCHOLOGIA Kesler, S. R., Garrett, A., Bender, B., Yankowitz, J., Zeng, S. M., Reiss, A. L. 2004; 42 (14): 1971-1978


    Turner syndrome (TS) results from partial or complete X-monosomy and is characterized by deficits in visuospatial functioning as well as social cognition and memory. Neuroimaging studies have demonstrated volumetric differences in the parietal region of females with TS compared to controls. The present study examined amygdala and hippocampus morphology in an attempt to further understand the neural correlates of psychosocial and memory functioning in TS. Thirty females with TS age 7.6-33.3 years (mean = 14.7 +/- 6.4) and 29 age-matched controls (mean age = 14.8 +/- 5.9; range = 6.4-32.7) were scanned using high resolution MRI. Volumetric analyses of the MRI scans included whole brain segmentation and manual delineation of the amygdala and hippocampus. Compared to controls, participants with TS demonstrated significantly larger left amygdala gray matter volumes, irrespective of total cerebral tissue and age. Participants with TS also showed disproportionately reduced right hippocampal volumes, involving both gray and white matter. Amygdala and hippocampal volumes appear to be impacted by X-monosomy. Aberrant morphology in these regions may be related to the social cognition and memory deficits often experienced by individuals with TS. Further investigations of changes in medial temporal morphology associated with TS are warranted.

    View details for DOI 10.1016/j.neuropsychologia.2004.04.021

    View details for Web of Science ID 000224330500012

    View details for PubMedID 15381027

  • Brain regions showing increased activation by threat-related words in panic disorder NEUROREPORT Maddock, R. J., Buonocore, M. H., Kile, S. J., Garrett, A. S. 2003; 14 (3): 325-328


    Threat-related stimuli consistently activate the posterior cingulate cortex in normal subjects and have exaggerated effects on memory in patients with panic disorder. We hypothesized that panic patients would show increased response to threat-related stimuli in the posterior cingulate cortex. While undergoing fMRI, six panic patients and eight healthy volunteers made valence judgements of threat-related and neutral words. Both groups showed threat-related activation in the left posterior cingulate and left middle frontal cortices, but the activation was significantly greater in panic patients. Panic patients also had more right>left asymmetry of activation in the mid-parahippocampal region. The increased responsivity observed in the posterior cingulate and dorsolateral prefrontal cortices is consistent with the hypothesis that panic disorder patients engage in more extensive memory processing of threat-related stimuli.

    View details for DOI 10.1097/01.wnr.0000059776.23521.25

    View details for Web of Science ID 000181641800006

    View details for PubMedID 12634477

  • Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task HUMAN BRAIN MAPPING Maddock, R. J., Garrett, A. S., Buonocore, M. H. 2003; 18 (1): 30-41


    Functional imaging studies consistently find that emotional stimuli activate the posterior cingulate cortex, a region that appears to have memory-related functions. However, prior imaging studies have not controlled for non-emotional stimulus features that might activate this region by engaging memory processes unrelated to emotion. This study examined whether emotional words activated the posterior cingulate cortex when these potentially confounding factors were controlled. Sixty-four pleasant and 64 unpleasant words were matched with neutral words on non-emotional features known to influence memory. Eight subjects underwent block-designed functional magnetic resonance imaging scans while evaluating the valence of these words. The posterior cingulate cortex was significantly activated bilaterally during both unpleasant and pleasant compared to neutral words. The strongest activation peak with both unpleasant and pleasant words was observed in the left subgenual cingulate cortex. Anteromedial orbital and left inferior and middle frontal cortices were also activated by both pleasant and unpleasant words. Right amygdala and auditory cortex were activated only by unpleasant words, while left frontal pole was activated only by pleasant words. The results show that activation of the posterior cingulate cortex by emotional stimuli cannot be attributed to the memory-enhancing effects of non-emotional stimulus features. The findings are consistent with the suggestion that this region may mediate interactions of emotional and memory-related processes. The results also extend prior findings that evaluating emotional words consistently activates the subgenual cingulate cortex, and suggest a means of probing this region in patients with mood disorders.

    View details for DOI 10.1002/hbm.10075

    View details for Web of Science ID 000179838400004

    View details for PubMedID 12454910

  • Time course of the subjective emotional response to aversive pictures: relevance to fMRI studies PSYCHIATRY RESEARCH-NEUROIMAGING Garrett, A. S., Maddock, R. J. 2001; 108 (1): 39-48


    Using functional magnetic resonance imaging (fMRI) to study brain activity related to the experience of emotion presents unique challenges to neuroscientists. One important consideration arises when an experimentally induced subjective emotional response persists after the end of the emotional stimulation epoch. In this case, brain activity related to the emotional response may continue during the subsequent control or comparison epoch. The comparison epoch of the experiment may then contain a lingering emotional response. This study was conducted to better understand the time course of the subjective emotional response to intensely aversive pictures, with the goal of applying this knowledge to the design and analysis of fMRI studies of emotion. A total of 18 women in two separate experiments were shown a series of aversive, neutral and scrambled pictures presented in alternating block designs. Subjects rated the intensity of their negative feelings every 4 s while viewing the pictures. Results indicate that the subjective emotional response persists well after the end of the emotional stimulation epoch. Following a 16-s block of aversive pictures, an average of an additional 16 s elapsed before self-reported negative feelings showed a 74-80% decline. These data suggest that fMRI studies of emotion should consider the time course of the subjective response to emotionally laden stimuli.

    View details for Web of Science ID 000172053800004

    View details for PubMedID 11677066

  • Remembering familiar people: The posterior cingulate cortex and autobiographical memory retrieval NEUROSCIENCE Maddock, R. F., Garrett, A. S., Buonocore, M. H. 2001; 104 (3): 667-676


    Most functional imaging studies of memory retrieval investigate memory for standardized laboratory stimuli. However, naturally acquired autobiographical memories differ from memories of standardized stimuli in important ways. Neuroimaging studies of natural memories may reveal distinctive patterns of brain activation and may have particular value in assessing clinical disorders of memory. This study used functional magnetic resonance imaging to investigate brain activation during successful retrieval of autobiographical memories elicited by name-cued recall of family members and friends. The caudal part of the left posterior cingulate cortex was the most strongly activated region and was significantly activated in all eight subjects studied. Most subjects also showed significant activation of the left anterior orbitomedial, anterior middle frontal, precuneus, cuneus, and posterior inferior parietal cortices, and the right posterior cingulate and motor cortices.Our findings are consistent with prior studies showing posterior cingulate cortex activation during autobiographical memory retrieval. This region is also consistently activated during retrieval of standardized memory stimuli when experimental designs emphasizing successful retrieval are employed. Our results support the hypothesis that the posterior cingulate cortex plays an important role in successful memory retrieval. The posterior cingulate cortex has strong reciprocal connections with entorhinal and parahippocampal cortices. Studies of early Alzheimer's disease, temporal lobectomy, and hypoxic amnesia show that hypometabolism of the posterior cingulate cortex is an early and prominent indicator of pathology in these patients. Our findings suggest that autobiographical memory retrieval tasks could be used to probe the functional status of the posterior cingulate cortex in patients with early Alzheimer's disease or at risk for that condition.

    View details for Web of Science ID 000169933100008

    View details for PubMedID 11440800

  • Cortical activity related to accuracy of letter recognition NEUROIMAGE Garrett, A. S., Flowers, D. L., Absher, J. R., Fahey, F. H., Gage, H. D., Keyes, J. W., Porrino, L. J., Wood, F. B. 2000; 11 (2): 111-123


    Previous imaging and neurophysiological studies have suggested that the posterior inferior temporal region participates in tasks requiring the recognition of objects, including faces, words, and letters; however, the relationship between accuracy of recognition and activity in that region has not been systematically investigated. In this study, positron emission tomography was used to estimate glucose metabolism in 60 normal adults performing a computer-generated letter-recognition task. Both a region of interest and a voxel-based method of analysis, with subject state and trait variables statistically controlled, found task accuracy to be: (1) negatively related to metabolism in the left ventrolateral inferior temporal occipital cortex (Brodmann's area 37, or ventrolateral BA 37) and (2) positively related to metabolism in a region of the right ventrolateral frontal cortex (Brodmann's areas 47 and 11, or right BA 47/11). Left ventrolateral BA 37 was significantly related both to hits and to false alarms, whereas the right BA 47/11 finding was related only to false alarms. The results were taken as supporting an automaticity mechanism for left ventrolateral BA 37, whereby task accuracy was associated with automatic letter recognition and in turn to reduced metabolism in this extrastriate area. The right BA 47/11 finding was interpreted as reflecting a separate component of task accuracy, associated with selectivity of attention broadly and with inhibition of erroneous responding in particular. The findings are interpreted as supporting the need for control of variance due to subject and task variables, not only in correlational but also in subtraction designs.

    View details for Web of Science ID 000085730200003

    View details for PubMedID 10679184