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1.  Reduced emotion processing efficiency in healthy males relative to females 
This study examined sex differences in categorization of facial emotions and activation of brain regions supportive of those classifications. In Experiment 1, performance on the Facial Emotion Perception Test (FEPT) was examined among 75 healthy females and 63 healthy males. Females were more accurate in the categorization of fearful expressions relative to males. In Experiment 2, 3T functional magnetic resonance imaging data were acquired for a separate sample of 21 healthy females and 17 healthy males while performing the FEPT. Activation to neutral facial expressions was subtracted from activation to sad, angry, fearful and happy facial expressions. Although females and males demonstrated activation in some overlapping regions for all emotions, many regions were exclusive to females or males. For anger, sad and happy, males displayed a larger extent of activation than did females, and greater height of activation was detected in diffuse cortical and subcortical regions. For fear, males displayed greater activation than females only in right postcentral gyri. With one exception in females, performance was not associated with activation. Results suggest that females and males process emotions using different neural pathways, and these differences cannot be explained by performance variations.
doi:10.1093/scan/nss137
PMCID: PMC3980801  PMID: 23196633
face emotion processing; affect perception; sex differences; gender differences
2.  Differential Prefrontal and Subcortical Circuitry Engagement During Encoding of Semantically Related Words in Patients with Late Life Depression 
Objective
Verbal memory difficulties are common among individuals with late-life depression (LLD), though there is limited knowledge about disruptions to underlying cerebral circuitry. The purpose of this study is to examine aberrations to cerebral networks implicated in encoding novel verbal semantic material among older adults with LLD.
Methods
Twenty-four older adults with early-onset LLD and 23 non-depressed comparisons (NDC) participated in the study. Participants completed a word list-learning task while undergoing fMRI.
Results
In the context of equivalent recall and recognition of words following scanning and similar hippocampal volumes, patients with LLD exhibited less activation in structures known to be relevant for new learning and memory, including hippocampus, parahippocampal gyrus, insula, and cingulate, relative to non-ill comparisons. An important region in which the LLD group displayed greater activation than the NDC group was in inferior frontal gyrus (IFG), an area involved in cognitive control and controlled semantic/phonological retrieval and analysis; this region may be critical for LLD patients to consolidate encoded words into memory.
Conclusions
Functional irregularities found in LLD patients may reflect different modes of processing to-be-remembered information and/or early changes predictive of incipient cognitive decline. Future studies might consider mechanisms that could contribute to these functional differences, including HPA-axis functioning and vascular integrity, and utilize longitudinal designs in order to understand whether functional changes are predictive of incipient cognitive decline.
doi:10.1002/gps.4165
PMCID: PMC4337801  PMID: 24948034
depression; memory; hippocampus; aging
3.  Impact of Chronic Hypercortisolemia on Affective Processing 
Neuropharmacology  2011;62(1):217-225.
Cushing syndrome (CS) is the classic condition of cortisol dysregulation, and cortisol dysregulation is the prototypic finding in Major Depressive Disorder (MDD). We hypothesized that subjects with active CS would show dysfunction in frontal and limbic structures relevant to affective networks, and also manifest poorer facial affect identification accuracy, a finding reported in MDD.Twenty-one patients with confirmed CS (20 ACTH-dependent and 1 ACTH-independent) were compared to 21 healthy controlsubjects. Identification of affective facial expressions (Facial Emotion Perception Test) was conducted in a 3 Tesla GE fMRI scanner using BOLD fMRI signal. The impact of disease (illness duration, current hormone elevation and degree of disruption of circadian rhythm), performance, and comorbid conditions secondary to hypercortisolemia were evaluated.CS patients made more errors in categorizing facial expressions and had less activation in left anterior superior temporal gyrus, a region important in emotion processing. CS patients showed higher activation in frontal, medial, and subcortical regions relative to controls. Two regions of elevated activation in CS, left middle frontal and lateral posterior/pulvinar areas, were positively correlated with accuracy in emotion identification in the CS group, reflecting compensatory recruitment. In addition, within the CSgroup, greater activation in left dorsal anterior cingulatewas related to greater severity of hormone dysregulation. In conclusion, cortisol dysregulation in CS patients is associated with problems in accuracy of affective discrimination and altered activation of brain structures relevant to emotion perception, processing and regulation, similar to the performance decrements and brain regions shown to be dysfunctional in MDD.
doi:10.1016/j.neuropharm.2011.07.006
PMCID: PMC3196277  PMID: 21787793
HPA; cortisol; ACTH; emotion; affect; fMRI; Cushings
4.  Frontal and Limbic Activation During Inhibitory Control Predicts Treatment Response in Major Depressive Disorder 
Biological psychiatry  2007;62(11):1272-1280.
Background
Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD.
Methods:
Twenty MDD and 22 control volunteer participants matched by age and gender completed a contextual inhibitory control task, the Parametric Go/No-go (PGNG) task during functional magnetic resonance imaging. The PGNG includes three levels of difficulty, a typical continuous performance task and two progressively more difficult versions including Go/No-go hit and rejection trials. After this test, 15 of 20 MDD patients completed a full 10-week treatment with s-citalopram.
Results:
There was a significant interaction among response time (control subjects better), hits (control subjects better), and rejections (patients better). The MDD participants had greater activation compared with the control group in frontal and anterior temporal areas during correct rejections (inhibition). Activation during successful inhibitory events in bilateral inferior frontal and left amygdala, insula, and nucleus accumbens and during unsuccessful inhibition (commission errors) in rostral anterior cingulate predicted post-treatment improvement in depression symptoms.
Conclusions:
The imaging findings suggest that in MDD subjects, greater neural activation in frontal, limbic, and temporal regions during correct rejection of lures is necessary to achieve behavioral performance equivalent to control subjects. Greater activation in similar regions was further predictive of better treatment response in MDD.
doi:10.1016/j.biopsych.2007.02.019
PMCID: PMC2860742  PMID: 17585888
Depression; executive functioning; fMRI; imaging; inhibitory control; mood disorders; SSRIs; treatment response
5.  An evaluation of distinct volumetric and functional MRI contributions toward understanding age and task performance: A study in the basal ganglia 
Brain research  2007;1135(1):58-68.
Prior work by our group and others has implicated the basal ganglia as important in age-related differences in tasks involving motor response control. The present study used structural and functional MRI approaches to analyze this region of interest (ROI) toward better understanding the contributions of structural and functional MRI measures to understanding age-related and task performance-related cognitive differences. Eleven healthy elders were compared with 11 healthy younger adults while they completed the “go” portion of a complex Go/No-go task. Separate ROI’s in the bilateral caudate (C) and putamen/globus pallidus (PGp) were studied based upon previous findings of age-related functional MRI differences in basal ganglia for this portion of the task. Structural volumes and functional activation (in percent area under the curve during correct responses) were independently extracted for these ROI’s. Results showed that age correlated with ROI volume in bilateral PGp and C, while multiple task performance measures correlated with functional activation in the left PGp. The Go/No-go task measures were also significantly correlated with traditional attention and executive functioning measures. Importantly, fMRI activation and volumes from each ROI were not significantly inter-correlated. These findings suggest that structural and functional MRI make unique contributions to the study of performance changes in aging.
doi:10.1016/j.brainres.2006.11.068
PMCID: PMC2078239  PMID: 17210145
Aging; fMRI; Imaging; Executive functioning; Attention Response execution; Motor skill

Results 1-5 (5)