Dataset Information

Altered amygdala circuits underlying valence processing among manic and depressed phases in bipolar adults.

ABSTRACT: BACKGROUND:Disruptions in affective processing characterize mood disorders, yet the neural mechanisms underlying internal state dependency in affective processes are not well understood. The present work presents a pilot investigation into state dependency among neural circuits known to be involved in processing affective information, by examining acute manic and depressive mood phases in adults with bipolar disorder and major depressive disorder. METHODS:The present study probed affective processes with a well-validated passive picture-viewing task amongst acutely manic (n?=?8) or acutely depressed (bipolar depression: n?=?11; major depression: n?=?15) mood-disordered adults during functional magnetic resonance imaging . RESULTS:Beta-series correlation analyses seeded from the amygdala revealed distinct neural circuits distinguished across current mood state rather than diagnostic boundaries. We delineated an amygdala-striatum pathway that distinguished depressed from manic mood phase, rather than between diagnostic boundaries, in processing valenced information. Specifically, we found differences in this neural response to negative, but not positive, images across clinical mood states. LIMITATIONS:As a preliminary investigation of state-dependent affective processes, the current investigation is predominantly limited by the small sample size. While it provides direction and generates hypotheses for further work, future studies need to replicate and expand the reported effects with larger samples. CONCLUSIONS:These findings demonstrate the conditions under which mood state-dependent affective processes cut cross traditional diagnostic boundaries, speaking to recent advances in transdiagnostic disease mechanisms, and can guide future work examining the neural mechanisms driving symptomatology in affective disorders.

SUBMITTER: Man V

PROVIDER: S-EPMC6351166 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Altered amygdala circuits underlying valence processing among manic and depressed phases in bipolar adults.

Man Vincent V Gruber June J Glahn David C DC Cunningham William A WA

Journal of affective disorders 20181103

<h4>Background</h4>Disruptions in affective processing characterize mood disorders, yet the neural mechanisms underlying internal state dependency in affective processes are not well understood. The present work presents a pilot investigation into state dependency among neural circuits known to be involved in processing affective information, by examining acute manic and depressive mood phases in adults with bipolar disorder and major depressive disorder.<h4>Methods</h4>The present study probed ...[more]

PMID: 30423467

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Project description:Animals perform innate behaviors that are stereotyped responses to specific evolutionarily relevant stimuli in the absence of prior learning or experience. These behaviors can be reduced to an axis of valence, whereby specific odors evoke approach and avoidance. The cortical amygdala (plCoA) mediates innate attraction and aversion to odor. However, little is known about how this brain area gives rise to behaviors of opposing motivational valence. Here, we sought to define the circuit features of plCoA that give rise to innate olfactory behaviors of valence. We characterized the physiology, gene expression, and projections of this structure, identifying a divergent, topographic organization that selectively controls innate attraction and avoidance to odor. First, we examined odor-evoked responses in these areas and found sparse encoding of odor identity, but not valence. We next considered a topographic organization and found that optogenetic stimulation of the anterior and posterior domains of plCoA elicits attraction and avoidance, respectively, suggesting a functional axis for valence. Using single cell and spatial RNA sequencing, we identified the molecular cell types in plCoA, revealing an anteroposterior gradient in cell types, whereby anterior glutamatergic neurons preferentially express Slc17a6 and posterior neurons express Slc17a7. Activation of these respective cell types recapitulates appetitive and aversive valence behaviors, and chemogenetic inhibition reveals partial necessity for valence responses to innate appetitive or aversive odors. Finally, we identified topographically organized circuits defined by projections, whereby anterior neurons preferentially project to medial amygdala, and posterior neurons preferentially project to nucleus accumbens, which are respectively sufficient and necessary for innate negative and positive olfactory valence. Together, these data advance our understanding of how the olfactory system generates stereotypic, hardwired attraction and avoidance, and supports a model whereby distinct, topographically distributed plCoA populations direct innate olfactory valence responses by signaling to divergent valence-specific targets, linking upstream olfactory identity to downstream valence behaviors, through a population code. This represents a novel circuit motif in which valence encoding is represented not by the firing properties of individual neurons, but by population level identity encoding that is routed through divergent targets to mediate distinct valence.

Project description:ContextPrematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce.ObjectiveTo compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants' amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months.ParticipantsEighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation.OutcomesAmygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months.ResultsAmygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm(3), p < 0.001), and overall right amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm(3), p < 0.001). White matter volumes were significantly smaller (p < 0.001) and CSF volumes significantly larger (p < 0.001) in preterm than in term born infants, while cortical and subcortical gray matter volumes were not significantly different between groups. Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm(3), p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode.ConclusionOur results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development might be linked to alterations in white matter connectivity reported in premature infants. Moreover, our data suggests that such alterations might affect infants' fear-processing capabilities.

Dataset Information

Altered amygdala circuits underlying valence processing among manic and depressed phases in bipolar adults.

Publications

Altered amygdala circuits underlying valence processing among manic and depressed phases in bipolar adults.

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