Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia

Abstract

Sensory processing deficits, first investigated by Kraeplin and Bleuler as possible pathophysiological mechanisms in schizophrenia, are now being re-characterized in the context of modern understanding of the involved molecular and neurobiological brain mechanisms. The National Institute of Mental Health Research Domain Criteria position these deficits as intermediaries between molecular and cellular mechanisms and clinical symptoms of schizophrenia such as hallucinations. The pre-pulse inhibition of startle responses by a weaker preceding tone, the inhibitory gating of response to paired sensory stimuli characterized using the auditory P50 evoked response, and the detection of slightly different stimuli that elicits the cortical Mismatch Negativity potential demonstrate deficits in early sensory processing mechanisms, whose molecular and neurobiological bases are increasingly well understood. Deficits in sensory processing underlie more complex cognitive dysfunction and, vice versa, are affected by higher-level cognitive difficulties. These deficits are now being used to identify genes involved in familial transmission of the illness and to monitor potentially therapeutic drug effects for both treatment and prevention. This research also provides a clinical reminder that patients’ sensory perception of the surrounding world, even during treatment sessions, may differ considerable from others’ perceptions. A person’s ability to understand and interact effectively with surrounding world ultimately depends upon an underlying sensory experience of it.

Global brain connectivity alterations in patients with schizophrenia and bipolar spectrum disorders

“…We anticipated centrality reductions in hub regions across patient groups, with stronger reductions associated with more severe symptoms. Further, we hypothesized altered centrality of regions involved in sensorimotor and perceptual processing; [20][21][22] centrality decreases in frontal, anterior cingulate, precuneus and parietal regions in patients with schizophrenia; 18 and aberrant limbic centrality in patients with BD. 15 In order to address questions pertaining to regional specificity, we performed fullbrain analyses with stringent corrections for multiple comparisons using permutation testing.…”

Disintegration of sensorimotor brain networks in schizophrenia

“…This is in line with previous studies documenting sensory and perceptual deficits in various domains from early-stage processing to cognitive stimulus interpretation. 39,40 The strong sensory involvement overlaps with findings from electroencephalogram studies, associating schizophrenia with a broad range of sensory deficits reflected among various eventrelated potentials (eg, reduced pre-pulse inhibition (PPI), MMN [mismatch negativity], P1, P3). 40 Our data support both focal (within sensorimotor/ visual nodes) and distal (between sensorimotor/visual and thalamus/higher-order nodes) connectivity differences in schizophrenia, including edges implicating dorsal attention, default mode, frontoparietal, and thalamus nodes.…”

“…39,40 The strong sensory involvement overlaps with findings from electroencephalogram studies, associating schizophrenia with a broad range of sensory deficits reflected among various eventrelated potentials (eg, reduced pre-pulse inhibition (PPI), MMN [mismatch negativity], P1, P3). 40 Our data support both focal (within sensorimotor/ visual nodes) and distal (between sensorimotor/visual and thalamus/higher-order nodes) connectivity differences in schizophrenia, including edges implicating dorsal attention, default mode, frontoparietal, and thalamus nodes. The thalamo-cortical functional disintegration in schizophrenia is in line with the prominent role of the thalamus in relaying and coordinating information between various cortical sources, including perceptual and motor processes, and supports a role of altered thalamus connectivity in the pathophysiology.…”

“…Thus, shifting future research focus from the cognitive to the sensory domain may enhance our understanding of schizophrenia pathophysiology. 40 …”

Neural mechanisms of mismatch negativity (MMN) dysfunction in schizophrenia

“…At the neurochemical and anatomical levels MMN has been shown to reflect impaired Nmethyl-D-aspartate receptor (NMDAR) function [12][13][14][15] at the level of supratemporal auditory cortex in schizophrenia 2,[15][16][17][18] . By contrast, ensemble-level processes contributing to MMN impairments have been studied to a lesser degree.…”