Current findings and perspectives on aberrant neural oscillations in schizophrenia

Abstract

There is now consistent evidence that neural oscillation at low‐ and high‐frequencies constitute an important aspect of the pathophysiology of schizophrenia. Specifically, impaired rhythmic activity may underlie the deficit to generate coherent cognition and behavior, leading to the characteristic symptoms of psychosis and cognitive deficits. Importantly, the generating mechanisms of neural oscillations are relatively well‐understood and thus enable the targeted search for the underlying circuit impairments and novel treatment targets. In the following review, we will summarize and assess the evidence for aberrant rhythmic activity in schizophrenia through evaluating studies that have utilized Electro/Magnetoencephalography to examine neural oscillations during sensory and cognitive tasks as well as during resting‐state measurements. These data will be linked to current evidence from post‐mortem, neuroimaging, genetics, and animal models that have implicated deficits in GABAergic interneurons and glutamatergic neurotransmission in oscillatory deficits in schizophrenia. Finally, we will highlight methodological and analytical challenges as well as provide recommendations for future research.

Long-range inhibition synchronizes and updates prefrontal task activity

“…In summary, our results reveal circuit mechanisms which switch the prefrontal cortex from maintaining to updating behavioral strategies, functions for interhemispheric GABAergic projections in the neocortex, roles for gamma synchrony in information processing beyond communication through coherence, and new forms of network plasticity. These findings identify a new callosal connection originating from prefrontal parvalbumin neurons as a critical circuit locus for understanding and modulating the deficits in gamma synchrony and behavioral flexibility that are major features of schizophrenia 9–10 .…”

“…Thus, callosal parvalbumin projections switch prefrontal circuits from maintaining to updating behavioral strategies by synchronizing callosal communication and preventing it from inappropriately maintaining outdated neural representations. These findings may explain how deficits in prefrontal parvalbumin neurons and gamma synchrony cause impaired behavioral flexibility in schizophrenia 9–10 , and identify long-range projections from prefrontal parvalbumin neurons as a key circuit locus for understanding and treating these deficits.…”

Toward recovery in schizophrenia: Current concepts, findings, and future research directions

“…More importantly, abnormalities in gamma-band oscillations are linked to current evidence from postmortem, genetic, and animal model studies that have implicated alterations in GABAergic interneurons and glutamatergic neurotransmission in schizophrenia. 67 For clinically relevant research, pharmacokinetic studies using PET showed increased D2 dopamine receptor (D2R) drug occupancy in the striatum of patients with schizophrenia, which provided one of the bases for the "dopamine hypothesis," a fundamental theory associated with treatment with antipsychotics. 79 PET studies also revealed that D2R drug occupancy needs to be maintained at 65-80% ("therapeutic window") to ensure a good balance between producing extrapyramidal syndromes and antipsychotic effects.…”

“…17 Specifically, patients are treated at the initial stage, when optimal treatment responsiveness is expected, and the response to the treatment is accurately and objectively evaluated 61,62,21,63,64 In addition, the recent development of brain imaging techniques has enabled us to view the structure, function, and chemical/metabolic composition of the brain in living subjects. While numerous diagnostic measures, such as salivary cortisol levels and blood markers of inflammation and oxidation, have been proposed for use in the context of schizophrenia 21,65 neuroimaging and neurophysiological methods, especially magnetic resonance imaging (MRI) and electroencephalography (EEG)/magnetencephalography (MEG), are potential diagnostic approaches with which we have accumulated much knowledge because of their noninvasiveness and frequent use in clinical settings 66,67 In addition, magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) enable us to evaluate abnormalities in chemical and metabolic changes in patient brains while they are living.…”

Optogenetic Methods to Investigate Brain Alterations in Preclinical Models

“…In humans, alterations in excitatory/inhibitory balance, neurodevelopmental processes and neuromodulation have been identified at cellular, molecular and synaptic level [ 150 ]. At the systems level, alterations in functional connectivity and synchrony, resulting in aberrant gamma oscillations in cognitive and sensory brain areas, have been shown to be present since the early onset of the disorder [ 151 , 152 ]. The neuronal circuits underlying such alterations remain largely to be identified, and a clear etiopathogenetic mechanism underlying SCZ is still missing.…”