Lateralization of Auditory Sensory Gating and Neuropsychological Dysfunction in Schizophrenia

Abstract

Objective: Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships. Method: Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures. Results: M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory. Conclusions: Converging evidence from E EG , ME G , a nd n europsycho logica l measures points to left hemisphere dysfunction as strongly related to the wellestablished sensory gating deficit in schizophrenia.

Cortical Evoked Response to Gaps in Noise: Within-Channel and Across-Channel Conditions

“…Specifically, the P1 is thought to be generated in the superior temporal gyrus, and is associated with auditory inhibition and sensory gating (Huotilainen, et al, 1998;Thoma, et al, 2003;Waldo, Gerhardt, Baker, Drebing, Adler, & Freedman, 1992). The N1 component is thought to reflect stimulus characteristics such as intensity and timing (Naatanen & Picton, 1987), and may be generated by activity in the superior temporal plane as well as other sources in the temporal and frontal lobes (Knight, Scabini, Woods, & Clayworth, 1988; Papanicolaou, Bau-mann, Rogers, Saydjari, Amparo, & Eisenberg, 1990;Scherg, Vajsar, & Picton, 1989).…”

“…Therefore, the P1-N1-P2 is particularly well suited for studying a number of acoustic cues important for the perception of speech, including silent gaps. These peaks occur approximately 50 ms (P1), 100 ms (N1), and 200 ms (P2) after stimulus onset and are thought to represent synchronous neural firing in the thalamic-cortical segment of the central auditory system in response to the onset of acoustic change (for review see Key, Dove, & Maguire, 2005; also Naatanen & Picton, 1987;Wolpaw & Penry, 1975;Woods, 1995).Specifically, the P1 is thought to be generated in the superior temporal gyrus, and is associated with auditory inhibition and sensory gating (Huotilainen, et al, 1998;Thoma, et al, 2003;Waldo, Gerhardt, Baker, Drebing, Adler, & Freedman, 1992). The N1 component is thought to reflect stimulus characteristics such as intensity and timing (Naatanen & Picton, 1987), and may be generated by activity in the superior temporal plane as well as other sources in the temporal and frontal lobes (Knight, Scabini, Woods, & Clayworth, 1988; Papanicolaou, Bau-mann, Rogers, Saydjari, Amparo, & Eisenberg, 1990;Scherg, Vajsar, & Picton, 1989).…”

Towards a functional topography of sensory gating areas: Invasive P50 recording and electrical stimulation mapping in epilepsy surgery candidates

“…Furthermore, there is now accumulating evidence from invasive EEG (Grunwald et al, 2003), EP source analyses (Weisser, 2001) and MEG (Thoma, 2003) studies that P50 sensory gating in a double-click paradigm is also topographically related to that sensory area. This is in accordance with the repeated finding of a cluster of superior posterior temporal P50max-sites in the present study and with the occurrence of a co-location of the sites with ESMassociated auditory pseudohallucinations and P50-gating in our patient no.…”

“…If an impairment in sensory gating in schizophrenic patients, at least in part, underlies sensory overload and attention dysfunctions in these patients, then the assumption of a "frontotemporal network" (Thoma, 2003) for gating is theoretically much more plausible than that of a modal bitemporal gating network. Attention, cognitive control, and top-down modulation of sensory input are mainly frontal functions that may be applied to an input which has already, in part, been "gated" modally in the respective sensory areas.…”

“…In a study with invasive P50 recordings from subdural strip and grid electrodes in epilepsy patients, Grunwald et al (2003) also found two major areas of P50 gating, one temporoparietal and one pre-and midfrontal. The insensitivity of the magnetoencephalography (MEG) for the detection of a frontal component (Weisser et al, 2001;Thoma et al, 2003) indicates that this frontal source may originate from deeper structures or have a radial orientation, as MEG is known to be relatively insensitive for both kinds of sources.…”