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Multiple techniques exist for the automated segmentation of magnetic resonance images (MRIs). The validity of these techniques can be assessed by evaluating test-retest reliability, inter-scanner reliability, and consistency with manual segmentation. We evaluate these measures for the FSL/FIRST subcortical segmentation tool. We retrospectively analyzed 190 MRI scans from 87 subjects with mood or anxiety disorders and healthy volunteers scanned multiple times on different platforms (N=56) and/or the same platform (N=45, groups overlap), and 146 scans from subjects who underwent both high-resolution and whole brain imaging in a single session, for comparison with manual segmentation of the hippocampus. The thalamus, caudate, putamen, hippocampus, and pallidum were reliably segmented in different sessions on the same scanner (ICC>0.83 scanners and diagnostic groups pooled). In these regions, the range of between-platform reliabilities were lower (0.5270.7, groups pooled), and both methods detected significant differences between genders. Additionally, FIRST segmentations were consistent with manual segmentations (in a subset of images; N=20) in the left caudate and bilateral putamen. This retrospective analysis assesses realistic performance of the algorithm in conditions like those found in multi-site trials or meta-analyses. Additionally, the inclusion of psychiatric patients establishes reliability in subjects exhibiting volumetric abnormalities, validating patient studies.

Objective-Hippocampal volume is reduced in posttraumatic stress disorder (PTSD). In the present study, we sought to determine whether volume loss is homogenously distributed or confined to certain part of the structure.Method-Twenty-two adult outpatients with PTSD (11 after prolonged prepubertal trauma and 11 after single adult trauma) and 22 matched healthy subjects were scanned at the National Institute of Mental Health using high-resolution 3T magnetic resonance imaging between September 2003 and August 2004. PTSD diagnosis was conferred using the Structured Clinical Interview for DSM-IV. Volumes of whole, anterior, and posterior hippocampus and subiculum were compared between groups.Results-Total hippocampal volume was lower in patients with PTSD (p = .2), with a significant diagnosis by hippocampal-subregion interaction (p = .2). Post hoc analysis revealed significantly smaller posterior hippocampi in PTSD (p = .006), with no difference in the volumes of anterior hippocampus or subiculum. No volume differences were found between PTSD participants with prolonged childhood abuse compared to single adult trauma exposure.Conclusions-The posterior hippocampus has been associated with storage, processing, and retrieval of spatiotemporal memories, central to the protective function of fear conditioning. Volume deficit in the posterior hippocampus may indicate malfunction in this faculty, leading to the exaggerated conditioned fear response observed in PTSD.

Objectives-Neuropsychological studies in subjects with bipolar disorder (BD) have reported deficits on a variety of cognitive measures. However, because the majority of subjects were medicated at the time of testing in previous studies, it is currently unclear whether the pattern of deficits reported is related to BD itself or to psychotropic medication. We addressed this issue by examining cognitive performance in a group of unmedicated, currently depressed subjects with BD.Methods-Forty-nine unmedicated subjects who met DSM-IV criteria for BD, depressed phase, and 55 control subjects participated in this study. Most patients were diagnosed with bipolar II disorder. Performance on emotion-dependent, or 'hot', and emotion-independent, or 'cold', cognitive tasks was assessed using tests from the Cambridge Neuropsychological Test Automated Battery.Results-The groups were well matched with respect to general intelligence and demographic variables. Deficits in the unmedicated depressed BD group were apparent on tests tapping 'hot' cognitive processing, for example the Cambridge Gamble task and the Probabilistic Reversal Learning task. However, other than a deficit on the Spatial Span test in the depressed BD subjects, the groups performed equivalently on most measures of 'cold' cognitive processing, for example visual memory, attention, and working memory.Conclusions-These data suggest that deficits on tests involving reward processing, short-term spatial memory storage, and sensitivity to negative feedback in depressed BD subjects represent an effect of the illness itself and not mood-stabilizing medication. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMost of the published neuropsychological investigations of cognitive function in bipolar disorder (BD) have been confounded by the effects of medication. While some studies reported that medicated subjects with BD performed worse than matched controls on a number of neuropsychological tests (1-5, see 6 for a review), it remains unclear whether these deficits are present in unmedicated subjects. Furthermore, while recent studies have reported less pronounced cognitive impairment in patients with bipolar II disorder (BD-II) than bipolar I disorder (BD-I) (3,7-10), in some studies BD-II patients had a different profile of medication than those with 8). The aim of this study was to determine whether cognitive impairment is observed in unmedicated subjects with BD in a group primarily comprising patients with a diagnosis of BD-II.There is some evidence that mood-stabilizing medications, such as lithium, might themselves result in cognitive impairment. While a recent review concluded that the net effect of lithium administration was probably protective (11), it has long been known that patients using such medications report a dulling of intellectual capacity and concentration difficulties (12), and a meta-analysis concluded that lithium administration may negatively affect motor speed and verbal memory (13). Furthermore, studies adminis...

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