Objective Bipolar disorder is associated with high risk for suicide behavior that often develops in adolescence/young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents/young adults with bipolar disorder with and without history of suicide attempts combines structural, diffusion tensor and functional magnetic resonance imaging methods to investigate implicated abnormalities in structural and functional connectivity within fronto-limbic systems. Method Participants with bipolar disorder included 26 with a prior suicide attempt and 42 without attempts. Regional gray matter volume, white matter integrity and functional connectivity during processing of emotional stimuli were compared between groups and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results Compared to the non-attempter group, the attempter group showed reductions in gray matter volume in orbitofrontal cortex, hippocampus and cerebellum; white matter integrity in uncinate fasciculus, ventral frontal and right cerebellum regions; and amygdala functional connectivity to left ventral and right rostral prefrontal cortex (p<0.05, corrected). In exploratory analyses, among attempters, right rostral prefrontal connectivity was negatively correlated with suicidal ideation (p<0.05), and left ventral prefrontal connectivity was negatively correlated with attempt lethality (p<0.05). Conclusions Adolescent/young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral fronto-limbic neural system subserving emotion regulation. Among suicide attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicide ideation and attempt lethality.

Objectives-In past decades, neuroimaging research in bipolar disorder has demonstrated a convergence of findings in an amygdala-anterior paralimbic cortex neural system. This paper reviews behavioral neurology literature that first suggested a central role for this neural system in the disorder and the neuroimaging evidence that supports it.Methods-Relevant articles are reviewed to provide an amygdala-anterior paralimbic cortex neural system model of bipolar disorder, including articles from the fields of behavioral neurology and neuroanatomy, and neuroimaging.Results-The literature is highly supportive of key roles for the amygdala, anterior paralimbic cortices, and connections among these structures in the emotional dysregulation of bipolar disorder. The functions subserved by their more widely distributed connection sites suggest that broader system dysfunction could account for the range of functions-from neurovegetative to cognitive-disrupted in the disorder. Abnormalities in some components of this neural system are apparent by adolescence, while others, such as those in rostral prefrontal regions, appear to progress over adolescence and young adulthood, suggesting a neurodevelopmental model of the disorder. However, some findings conflict, which may reflect the small sample sizes of some studies, and clinical heterogeneity and methodological differences across studies.Conclusions-Consistent with models derived from early behavioral neurology studies, neuroimaging studies support a central role for an amygdala-anterior paralimbic neural system in bipolar disorder, and implicate abnormalities in the development of this system in the disorder. This system will be an important focus of future studies on the developmental pathophysiology, detection, treatment, and prevention of the disorder. OverviewNeuroimaging research over the past several decades has yielded a convergent view of bipolar disorder (BD) that supports a central role for an amygdala-anterior paralimbic cortex neural system in the disorder. This model draws from early behavioral neurology reports of lesions in anterior paralimbic cortices and seizure foci in mesial temporal structures, such as the amygdala, in patients whose symptoms were similar to those of individuals with primary mood disorders. It also draws from neuroanatomic and neurobehavioral studies, which identified connections among the amygdala and anterior paralimbic structures, including the ventral prefrontal cortex (VPFC), insular cortex (IC), and temporopolar cortex (TPC), and the central role of this system of interconnected structures in emotional regulation. These studies also identified more widely distributed connection sites of this system including more rostral, dorsal and lateral prefrontal cortices (PFC), hippocampus, striatum, thalamus, cerebellum and hypothalamus (1-5). Together, the structures of this system subserve the phylogenetically broad range of functions characteristically disrupted in BD, from basic biological rhythm and neurovegetative processes, s...

Objectives Convergent evidence supports limbic, anterior paralimbic, and prefrontal cortex (PFC) abnormalities in emotional processing in bipolar disorder (BD) and suggests that some abnormalities are mood-state-dependent and others persist into euthymia. However, few studies have assessed elevated, depressed, and euthymic mood states while individuals processed emotional stimuli of varying valence to investigate trait- and state-related neural system responses. Here, regional brain responses to positive, negative, and neutral emotional stimuli were assessed in individuals with BD during elevated, depressed, and euthymic mood states. Methods One hundred and thirty-four subjects participated in functional magnetic resonance imaging scanning while processing faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in elevated mood states, 19 depressed, 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait- and mood-state-related features. Results Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), and ventral striatum responses to happy and neutral faces were decreased in the BD group, compared to the HC group, and were not influenced by mood state. Elevated mood states were associated with decreased right rostral PFC activation to fearful and neutral faces, and depression was associated with increased left OFC activation to fearful faces. Conclusions The findings suggest that abnormal VACC, OFC, and ventral striatum responses to happy and neutral stimuli are trait features of BD. Acute mood states may be associated with additional lateralized abnormalities of diminished right rostral PFC responses to fearful and neutral stimuli in elevated states and increased left OFC responses to fearful stimuli in depressed states.

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Background: In critical care settings, electroencephalography (EEG) with reduced number of electrodes (reduced montage EEG, rm-EEG) might be a timely alternative to the conventional full montage EEG (fm-EEG). However, past studies have reported variable accuracies for detecting seizures using rm-EEG. We hypothesized that the past studies did not distinguish between differences in sensitivity from differences in classification of EEG patterns by different readers. The goal of the present study was to revisit the diagnostic value of rm-EEG when confounding issues are accounted for. Methods: We retrospectively collected 212 adult EEGs recorded at Massachusetts General Hospital and reviewed by two epileptologists with access to clinical, trending, and video information. In Phase I of the study, we re-configured the first 4 h of the EEGs in lateral circumferential montage with ten electrodes and asked new readers to interpret the EEGs without access to any other ancillary information. We compared their rating to the reading of hospital clinicians with access to ancillary information. In Phase II, we measured the accuracy of the same raters reading representative samples of the discordant EEGs in full and reduced configurations presented randomly by comparing their performance to majority consensus as the gold standard. Results: Of the 95 EEGs without seizures in the selected fm-EEG, readers of rm-EEG identified 92 cases (97%) as having no seizure activity. Of 117 EEGs with "seizures" identified in the selected fm-EEG, none of the cases was labeled as normal on rm-EEG. Readers of rm-EEG reported pathological activity in 100% of cases, but labeled them as seizures (N = 77), rhythmic or periodic patterns (N = 24), epileptiform spikes (N = 7), or burst suppression (N = 6). When the same raters read representative epochs of the discordant EEG cases (N = 43) in both fm-EEG and rm-EEG configurations, we found high concordance (95%) and intra-rater agreement (93%) between fm-EEG and rm-EEG diagnoses. Conclusions: Reduced EEG with ten electrodes in circumferential configuration preserves key features of the traditional EEG system. Discrepancies between rm-EEG and fm-EEG as reported in some of the past studies can be in part due to methodological factors such as choice of gold standard diagnosis, asymmetric access to ancillary clinical information, and inter-rater variability rather than detection failure of rm-EEG as a result of electrode reduction per se.