Biology subjects

Uhlhaas, P. J.

Publications and source records attributed to Uhlhaas, P. J..

3 recordsLinked to original sources

bioRxiv2024

Reconfiguration of Functional Brain Hierarchy in Schizophrenia

The multidimensional nature of schizophrenia requires a comprehensive exploration of the functional and structural brain networks. While prior research has provided valuable insights into these aspects, our study goes a step further to investigate the reconfiguration of the hierarchy of brain dynamics, which can help understand how brain regions interact and coordinate in schizophrenia. We applied an innovative thermodynamic framework, which allows for a quantification of the degree of functional hierarchical organization by analysing resting state fMRI-data. Our findings reveal increased hierarchical organization at the whole-brain level and within specific resting-state networks in individuals with schizophrenia, which correlated with negative symptoms, positive formal thought disorder and apathy. Moreover, using a machine learning approach, we showed that hierarchy measures allow a robust diagnostic separation between healthy controls and schizophrenia patients. Thus, our findings provide new insights into the nature of functional connectivity anomalies in schizophrenia, suggesting that they could be caused by the breakdown of the functional orchestration of brain dynamics.

neuroscience↗

bioRxiv2024

Large-scale Dynamical Fingerprints of Distributed Synaptic Alterations in Early-Stage Psychosis

Psychotic disorders, such as schizophrenia, present a major challenge for research and clinical practice: its pathogenesis is complex, the individual symptomatology is heterogenous, and there is a lack of biomarkers for the early detection, diagnosis, and individualized treatment. Mounting evidence indicates that the synaptic and microcircuitry alterations underlying psychosis are widely distributed in the brain. Here, we developed a magnetoencephalography approach to map the resulting alterations of local cortical population dynamics across the human cerebral cortex. We identified large-scale patterns of changes in neural dynamics that were remarkably similar between first-episode psychosis patients and individuals at clinical high risk for psychosis. These spatial patterns also resembled those induced by pharmacological manipulations of excitatory NMDA glutamate receptors and inhibitory GABA-A receptors in healthy participants. Differences in those spatial patterns of cortical dynamics between psychosis patients related to individual symptomatology. Our study opens a new window on the distributed pathophysiology of psychosis. TeaserCortex-wide changes in neural mass dynamics due to psychosis resemble changes due to GABA-A or NMDA receptor manipulation and relate to clinical symptoms.

neuroscience↗

bioRxiv2023

40 Hz Steady-State Responses in Human Auditory Cortex Depend on GABAergic Neuronal Inhibition

The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography (MEG) recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants. All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under placebo. The GABAA receptor-agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition. Significance statementThe 40 Hz auditory steady-state response is a candidate non-invasive biomarker for schizophrenia and related neuropsychiatric disorders. Yet, the understanding of the synaptic basis of this neurophysiological signature in humans has remained incomplete. We combined magnetoencephalography (MEG) recordings with placebo-controlled pharmacological interventions in healthy human subjects to test the modulation of the 40 Hz ASSR in auditory cortex by two synaptic components that have been implicated in the generation of neuronal oscillations in cortical microcircuits: glutamate N-methyl-aspartate glutamate (NMDA) receptors and gamma-amino-butyric acid (GABA) -A receptors. Boosting GABAergic transmission, but not blocking NMDA-receptors, increased the amplitude of this ASSR. Thus, GABAergic inhibition modulates 40 Hz steady-state responses in auditory cortex.

neuroscience↗