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bioRxiv

62 papers in the library · 96 citations · publishing 2018-2026

Papers

Neural substrates of cognitive impairment in a NMDAR hypofunction mouse model of schizophrenia and rescue by risperidone

bioRxiv January 18, 2023 Cristina Delgado-Sallent, Thomas Gener, Pau Nebot et al. preprint

In mice with NMDAR hypofunction induced by subchronic phencyclidine (PCP), memory and auditory perception impairments are linked to disrupted connectivity between the medial prefrontal cortex and the dorsal hippocampus. Short-term memory relies on high gamma connectivity from the prefrontal cortex to the hippocampus, while long-term memory retrieval depends on theta connectivity from the hippocampus to the prefrontal cortex. Subchronic PCP impairs both short-term and long-term memory, increases prefrontal activity, decreases hippocampal activity, and disrupts this connectivity. Two weeks of daily risperidone rescues memory deficits, attenuates hippocampal desynchronization, and also ameliorates auditory perception impairments and their neural correlates.

Network analysis of the human structural connectome including the brainstem

bioRxiv July 22, 2022 Salma Salhi, Youssef Kora, Gisu Ham et al.

A computational graph-theoretic analysis of the human structural connectome, incorporating subcortical structures including the brainstem, finds that the brainstem ranks highest across degree, eigenvector, and betweenness centrality metrics. The averaged connectome was derived from 100 healthy adult subjects using Python DIPY and Nibabel libraries. The results indicate the importance of including the brainstem in structural network analyses and suggest that such network-based methods can inform theories of consciousness, including global workspace theory, integrated information theory, and the thalamocortical loop theory.

Behavioural and molecular characterisation of the Dlg2 haploinsufficiency rat model of genetic risk for psychiatric disorder

bioRxiv October 12, 2021 Sophie Waldron, Rachel Pass, Simonas Griesius et al.

Genetic evidence links disruptions in the DLG2 gene to increased risk for schizophrenia, autism, and intellectual disability. To explore psychiatric traits associated with reduced DLG2 function, a rat model with one functional copy of the Dlg2 gene (Dlg2+/-) was tested for anxiety, sensorimotor gating, reward responses, social behavior, and movement after phencyclidine administration. The rats showed reduced PSD-93 mRNA and protein without compensation from related genes. They exhibited an exaggerated locomotor response to phencyclidine, a hallmark of psychosis models, but no deficits in other behaviors. These findings suggest that DLG2 haploinsufficiency produces subtle, psychosis-related effects, unlike the more severe impairments seen in models with complete gene loss.

Physiological basis underlying antidepressant-induced activation of TrkB receptors

bioRxiv August 31, 2021 O. Alitalo, S. Kohtala, Marko Rosenholm et al. preprint

Both pharmacological and non-pharmacological treatments for depression activate TrkB receptors—a known antidepressant target—by inducing a physiological response linked to sedation. Rapid-acting antidepressants trigger TrkB signaling by evoking a state characterized by electroencephalographic slow-wave activity, behavioral immobility, reduced cerebral glucose utilization, and lowered body temperature. This signaling was not impaired in animals with reduced activity-dependent BDNF release but was diminished by maintaining animals in a warm ambient temperature. Preventing the hypothermic response attenuated the behavioral effects of the rapid-acting antidepressant nitrous oxide. The findings suggest that changes in energy expenditure and thermoregulation are essential, but not sufficient, for antidepressant responses, challenging pharmacology-centric hypotheses and highlighting the role of bioenergetics and thermoregulation.

Mapping the subcortical connectivity of the human default mode network

bioRxiv July 14, 2021 Jian Li, W. Curley, B. Guérin et al. preprint

The default mode network (DMN) supports self-awareness and introspection, key to consciousness. Using 7 Tesla resting-state functional MRI data from 168 healthy volunteers and a novel NASCAR tensor decomposition method, researchers mapped DMN subcortical connectivity. They found that signals in the central lateral thalamus and ventral tegmental area strongly correlate with the DMN, with additional sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei. The putamen and globus pallidus are anti-correlated with the DMN, supporting the mesocircuit hypothesis of consciousness. This map can guide therapeutic neuromodulation targets for patients with disorders of consciousness.

A Dynamic Affective Core to bind the Contents, Context, and Value of Conscious Experience

bioRxiv May 21, 2021 K. Kishida, L. P. Sands preprint

Conscious subjective experience is private and dynamic, posing a challenge that neuroscience often sidesteps by focusing on information processing and behavior rather than the 'hard problem' of how neural activity produces phenomenal experience. Computational methods combined with brain-measurement tools are beginning to link dynamic changes in subjective affect with reproducible neurobehavioral signals. Research applying reinforcement learning theory has revealed connections between dopaminergic signals and changes in subjective affect, though dopamine alone cannot explain all affective dynamics. The authors review foundational work, highlight open questions, and propose a Dynamic Affective Core Hypothesis integrating how conscious experiences represent content and context with how they acquire affective subjective value.

Decrease of Functional Connectivity within the Default Mode Network by a Brief Training of Focused Attention on the Breath in Novices

bioRxiv February 12, 2021 S. Trova, Yukie Tsuji, Haruka Horiuchi et al. preprint

Six days of focused-attention meditation training in novices reduces functional connectivity within the default mode network (DMN), specifically between the ventromedial prefrontal cortex and the posterior cingulate cortex in theta and alpha bands, as measured by electroencephalography. This change correlates with increased state-level mindfulness scores. The findings indicate that even brief meditation practice can modify DMN activity in beginners.

Higher-order sensorimotor circuit of the brain’s global network supports human consciousness

bioRxiv September 23, 2020 Pengmin Qin, Xuehai Wu, Changwei W Wu et al. preprint

Local brain regions may support consciousness by acting as hubs within the brain's global network. Using resting-state fMRI data from people in various conscious states—NREM-sleep, REM-sleep, anesthesia, and brain injury patients—and a graph-theoretical measure for detecting local hubs, the authors identify higher-order sensory and motor regions whose degree centrality is significantly reduced during unconsciousness. These regions form a sensorimotor circuit that correlates with levels of consciousness. The findings suggest that integration of higher-order sensorimotor function may be a key mechanism of consciousness, opening novel perspectives for therapeutic modulation of unconsciousness.

Subjective visibility report is facilitated by conscious predictions only

bioRxiv July 9, 2020 Josipa Alilovic, H. Slagter, S. van Gaal preprint

Valid predictions improve conscious perception of a second target in an attentional blink task, but only when the predictive first target is consciously seen. Unseen first targets do not produce this benefit, regardless of the time interval between targets. The findings clarify how predictive processing and conscious access interact.

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia

bioRxiv November 2, 2019 R. Limongi, P. Jeon, M. Mackinley et al. preprint

Psychosis may arise from disrupted brain connectivity caused by insufficient NMDA receptor activity. In a study of 20 people with first-episode psychosis and 20 healthy controls, glutamate levels in the dorsal anterior cingulate cortex (dACC) were linked to altered inhibitory connections within the salience network. Specifically, higher glutamate correlated with weaker inhibitory influence on excitatory neurons in the dACC among those with psychosis. Abnormalities in cognitive-control task performance were tied to these disrupted connections, and the strength of connections from the dACC to the anterior insula was inversely related to social withdrawal severity. The findings suggest that glutamate-driven disinhibition contributes to connectivity deficits and cognitive impairments in psychosis.

Visual signals suppress Alpha Power Increases & Frequency Decreases before and after a Mindfulness Meditation Intervention for Problem Gambling

bioRxiv June 29, 2018 Kaili-Larissa Martin, Farah Jindani, N. Turner et al. preprint

Mindfulness meditation has been used effectively for over five years to treat problem gambling, but the neural mechanisms behind the improvements were unknown. Using resting-state electroencephalography, researchers measured changes in alpha oscillations before and after an eight-week mindfulness meditation intervention and a pre/post five-minute mindfulness meditation body scan in people with problem gambling. After the eight-week intervention, alpha power increased and alpha peak frequency decreased, while the opposite occurred after the brief body scan. The largest alpha rhythm changes were in the frontal and temporal lobes, areas involved in reward and sensory processing. These changes may reflect improved attentional control.