How brain activity is synchronized across individuals during narrative comprehension has previously been characterized by functional magnetic resonance imaging (fMRI) in healthy and patient populations. To our knowledge, there has been limited investigation as to how it is affected by major depressive disorder (MDD). We addressed this issue with fMRI through examination of inter-subject synchronization in the default mode network (DMN), brain structures which have previously been implicated in MDD pathology. Twenty-two patients with MDD and 20 matched control participants listened to Intact versus Scrambled versions of an auditory narrative; these experimental conditions differed in the degree of temporal integration they demanded. Across conditions, we found a significant increase in synchrony within DMN for intact narratives. As compared to controls, patients demonstrated a significant increase in synchrony across multiple DMN regions, some specific for intact narratives. Our findings highlight the impact of brain abnormalities in MDD on an ecologically relevant cognitive function.

γ-Aminobutyric acid (GABA), a primary inhibitory neurotransmitter in the brain, plays a significant role in aging and in neurodegenerative disorders, including Alzheimer’s disease (AD). We investigated the relationship between GABA levels in the dorsomedial/dorsoanterolateral prefrontal cortex (DM/DA-PFC) and memory in high-AD risk participants. Thirty-eight participants (14 Cognitively Normal [CN], 11 with Subjective Cognitive Decline (SCD), and 13 Mild Cognitive Impairment [MCI]) underwent magnetic resonance spectroscopy at 3 Tesla. SCD and MCI participants were grouped together to form a single high-AD risk group (N = 24) for the purposes of statistical analyses. Partial correlations of GABA+/Cr level with verbal memory, assessed on California Verbal Learning Test-II, and nonverbal memory, assessed on Brief Visuospatial Memory Test and Rey-Osterrieth test, were examined separately within the high-AD risk and CN groups. GABA+/Cr levels were positively correlated with long-delayed verbal memory (r = 0.69, P = 0.009) and immediate nonverbal memory (r = 0.97, P = 0.03) in high-AD risk, but not in CN participants. These results remained significant after controlling for depression. These preliminary findings, which require replication due to the limited sample sizes, are the first report of an association between GABA+/Cr levels within the DM/DA-PFC and memory performance in high-AD risk individuals.