Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia

Diminished synaptic gain - the sensitivity of postsynaptic responses to neural inputs - may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms. Participants with schizophrenia (Scz, n=108), their relatives (n=57), and controls (n=107) underwent three electroencephalography paradigms - resting, mismatch negativity, and 40 Hz auditory steady-state response - and resting functional magnetic resonance imaging. Dynamic causal modelling was used to quantify synaptic connectivity in cortical microcircuits. Across all four paradigms, characteristic Scz data features were best explained by models with greater self-inhibition (decreased synaptic gain), in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in Scz, in three paradigms. Thus, psychotic symptoms of Scz may result from a downregulation of inhibitory interneurons that may compensate for diminished postsynaptic gain in pyramidal cells.

A Photoelectric-Stimulated MoS2 Transistor for Neuromorphic Engineering

The von Neumann bottleneck has spawned the rapid expansion of neuromorphic engineering and brain-like networks. Synapses serve as bridges for information transmission and connection in the biological nervous system. The direct implementation of neural networks may depend on novel materials and devices that mimic natural neuronal and synaptic behavior. By exploiting the interfacial effects between MoS2 and AlOx, we demonstrate that an h-BN-encapsulated MoS2 artificial synapse transistor can mimic the basic synaptic behaviors, including EPSC, PPF, LTP, and LTD. Efficient optoelectronic spikes enable simulation of synaptic gain, frequency, and weight plasticity. The Pavlov classical conditioning experiment was successfully simulated by electrical tuning, showing associated learning behavior. In addition, h-BN encapsulation effectively improves the environmental time stability of our devices. Our h-BN-encapsulated MoS2 artificial synapse provides a new paradigm for hardware implementation of neuromorphic engineering.

The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder

New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stress-related synaptic dysconnectivity in the neurobiology and treatment of PTSD. Here, we integrate this perspective within a broader framework—in other words, a dual pathology model of ( a) stress-related synaptic loss arising from amino acid–based pathology and ( b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy.