The Amygdala in Schizophrenia and Bipolar Disorder: A Synthesis of Structural MRI, Diffusion Tensor Imaging, and Resting-State Functional Connectivity Findings.

Frequently implicated in psychotic spectrum disorders, the amygdala serves as an important hub for elucidating the convergent and divergent neural substrates in schizophrenia and bipolar disorder, the two most studied groups of psychotic spectrum conditions. A systematic search of electronic databases through December 2017 was conducted to identify neuroimaging studies of the amygdala in schizophrenia and bipolar disorder, focusing on structural MRI, diffusion tensor imaging (DTI), and resting-state functional connectivity studies, with an emphasis on cross-diagnostic studies. Ninety-four independent studies were selected for the present review (49 structural MRI, 27 DTI, and 18 resting-state functional MRI studies). Also selected, and analyzed in a separate meta-analysis, were 33 volumetric studies with the amygdala as the region-of-interest. Reduced left, right, and total amygdala volumes were found in schizophrenia, relative to both healthy controls and bipolar subjects, even when restricted to cohorts in the early stages of illness. No volume abnormalities were observed in bipolar subjects relative to healthy controls. Shape morphometry studies showed either amygdala deformity or no differences in schizophrenia, and no abnormalities in bipolar disorder. In contrast to the volumetric findings, DTI studies of the uncinate fasciculus tract (connecting the amygdala with the medial- and orbitofrontal cortices) largely showed reduced fractional anisotropy (a marker of white matter microstructure abnormality) in both schizophrenia and bipolar patients, with no cross-diagnostic differences. While decreased amygdalar-orbitofrontal functional connectivity was generally observed in schizophrenia, varying patterns of amygdalar-orbitofrontal connectivity in bipolar disorder were found. Future studies can consider adopting longitudinal approaches with multimodal imaging and more extensive clinical subtyping to probe amygdalar subregional changes and their relationship to the sequelae of psychotic disorders.

Getting Lost Behavior in Patients with Mild Alzheimer's Disease: A Cognitive and Anatomical Model.

BACKGROUND: Getting lost behavior (GLB) in the elderly is believed to involve poor top-down modulation of visuospatial processing, by impaired executive functions. However, since healthy elderly and elderly with Alzheimer's disease (AD) experience a different pattern of cognitive decline, it remains unclear whether this hypothesis can explain GLB in dementia. OBJECTIVE: We sought to identify whether poor executive functions and working memory modulate the relationship between visuospatial processing and prevalence of GLB in healthy elderly and patients with AD. Complementary to this, we explored whether brain regions critical for executive functions modulate the relationship between GLB and brain regions critical for visuospatial processing. METHOD: Ninety-two participants with mild AD and 46 healthy age-matched controls underwent neuropsychological assessment and a structural MRI. GLB was assessed using a semistructured clinical interview. Path analysis was used to explore interactions between visuospatial deficits, executive dysfunction/working memory, and prevalence of GLB, in AD and controls independently. RESULTS: For both healthy controls and patients with mild AD, visuospatial processing deficits were associated with GLB only in the presence of poor working memory. Anatomically, GLB was associated with medial temporal atrophy in patients with mild AD, which was not strengthened by low frontal gray matter (GM) volume as predicted. Instead, medial temporal atrophy was more strongly related to GLB in patients with high frontal GM volumes. For controls, GLB was not associated with occipital, parietal, medial temporal, or frontal GM volume. CONCLUSION: Cognitively, a top-down modulation deficit may drive GLB in both healthy elderly and patients with mild AD. This modulation effect may be localized in the medial temporal lobe for patients with mild AD. Thus, anatomical substrates of GLB in mild AD may not follow the typical top-down modulation mechanisms often reported in the healthy aging population. Implications advance therapeutic practices by highlighting the need to target both working memory and visuospatial deficits simultaneously, and that anatomical substrates of GLB may be disease specific.