Objective Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions, in BD. Methods Thirty-three individuals with BD and 31 healthy comparison participants (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results Functional connectivity was decreased between the pACC and amygdala in the BD group, compared to HC group, during the processing of fearful and happy faces (p<0.005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter including the region of the uncinate fasciculus was identified (p<0.005). Conclusion This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Objective-Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BD). In this study, we used complementary diffusion tensor imaging (DTI) methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods-Subjects included 33 participants with BD and 40 healthy comparison participants.Fractional anisotropy (FA) measures were compared between groups using region of interest (ROI) methods to investigate the anterior, middle and posterior CC and voxel-based methods to further localize abnormalities.Results-In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BD group (P<0.05). Voxel-based analyses similarly localized group differences to the genu, rostral body and anterior midbody of CC (P<0.05, corrected).Conclusion-The findings demonstrate abnormalities in the structural integrity of the anterior CC in BD which may contribute to altered inter-hemispheric connectivity in this disorder.The anterior corpus callosum (CC) has been implicated in bipolar disorder (BD) since at least 1903 when Starr described symptoms detected after anterior CC lesions similar to those of BD, such as "undue excitement, causeless laughter, unusual crying, great depression and a lack of harmony between the association of ideas and the state of feeling which they should awaken" (1). An early magnetic resonance imaging (MRI) study of cerebral morphology in BD detected mid-sagittal CC area decreases (2). Subsequent structural MRI studies provided further evidence for CC white matter abnormalities in BD including in volume, signal intensity Corresponding Author: Fei Wang, M.D., Ph.D. Department of Psychiatry, Yale University School of Medicine, Mailing Address: 300 George Street, Suite 901, New Haven, CT 06511, Phone: 203-785-6180, Fax: 203-737-2513, email: fei.wang@yale.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and structural integrity (3-5), although reports varied in the CC subregions studied and regional differences detected. In this study, complementary diffusion tensor imaging (DTI) region of interest (ROI) and voxel-based methods were used to study the structural integrity of CC white matter in BD and assess the regional localization of differences. Anterior CC reductions in FA in BD were anticipated. Methods ParticipantsThe Structured Clinical Interview for DSM-IV Axis I Disorders Version 2.0 (SCID) (6) confirmed the presence or absence of Axis I Disorders and mood state at scanning for the 33 BD and 40 healt...

Information processing speed was assessed using the visual threshold serial addition test (VT-SAT), a computerized modification of the PASAT designed to assess processing speed by controlling for performance accuracy. Persons with MS (N=43) and healthy individuals (N=32) were administered the VT-SAT varying working memory loads (1-back versus 2-back). Results indicated that at the lower working memory load (1-back) all individuals with MS were able to achieve a working memory performance level equivalent to healthy individuals, but required significantly more processing time to do so. In contrast, at the higher working memory load (2-back), about 70% of MS participants were able to achieve a performance level equivalent to healthy individuals, but again required significantly more processing time. The results are discussed in the context of the dynamic nature of the relationship between processing speed and working memory performance, emphasizing the dependence of this relationship on other cognitive and disease-related factors.