Biology subjects

Kunugi, H.

Publications and source records attributed to Kunugi, H..

3 recordsLinked to original sources

bioRxiv2021

The cerebellum as a moderator of negative bias of facial expression processing in depressive patients

BackgroundNegative bias--a mood-congruent bias in emotion processing--is an important aspect of major depressive disorder (MDD), and such a bias in facial expression recognition has a significant effect on patients social lives. Neuroscience research shows abnormal activity in emotion-processing systems regarding facial expressions in MDD. However, the neural basis of negative bias in facial expression processing has not been explored directly. MethodsSixteen patients with MDD and twenty-three healthy controls (HC) who underwent an fMRI scan during an explicit facial emotion task with happy to sad faces were selected. We identified brain areas in which the MDD and HC groups showed different correlations between the behavioral negative bias scores and functional activities. ResultsBehavioral data confirmed the existence of a higher negative bias in the MDD group. Regarding the relationship with neural activity, higher activity of happy faces in the posterior cerebellum was related to a higher negative bias in the MDD group, but lower negative bias in the HC group. LimitationsThe sample size was small, and the possible effects of medication were not controlled for in this study. ConclusionsWe confirmed a negative bias in the recognition of facial expressions in patients with MDD. fMRI data suggest the cerebellum as a moderator of facial emotion processing, which biases the recognition of facial expressions toward their own mood.

neuroscience↗

bioRxiv2021

Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimers disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

neuroscience↗

bioRxiv2019

AUTS2 regulation of synapses for proper synaptic inputs and social communication.

Impairments in synapse development are thought to cause numerous psychiatric disorders. Autism susceptibility candidate 2 (AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in the Auts2-deficient primary cultured neurons as well as Auts2 mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression in Auts2 mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability. Auts2 mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals with AUTS2 mutations.

neuroscience↗