Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia

Abstract

A critical component of cognitive impairments in schizophrenia can be characterized as a disturbance in cognitive control, or the ability to guide and adjust cognitive processes and behavior flexibly in accordance with one's intentions and goals. Cognitive control impairments in schizophrenia are consistently linked to specific disturbances in prefrontal cortical functioning, but the underlying neurophysiologic mechanisms are not yet well characterized. Synchronous gamma-band oscillations have been associated with a wide range of perceptual and cognitive processes, raising the possibility that they may also help entrain prefrontal cortical circuits in the service of cognitive control processes. In the present study, we measured induced gamma-band activity during a task that reliably engages cognitive control processes in association with prefrontal cortical activations in imaging studies. We found that higher cognitive control demands were associated with increases in induced gamma-band activity in the prefrontal areas of healthy subjects but that control-related modulation of prefrontal gamma-band activity was absent in schizophrenia subjects. Disturbances in gamma-band activity in patients correlated with illness symptoms, and gamma-band activity correlated positively with performance in control subjects but not in schizophrenia patients. Our findings may provide a link between previously reported postmortem abnormalities in thalamofrontocortical circuitry and alterations in prefrontal activity observed in functional neuroimaging studies. They also suggest that deficits in frontal cortical gamma-band synchrony may contribute to the cognitive control impairments in schizophrenia.

Fig. 1.

Cognitive task description. (Left) Low-control trials signaled by green cues. (Right) High-control trials signaled by red cues.

Fig. 2.

Behavioral data. Error rates (ER) and reaction times (RT) for low-control (green) and high-control (red) trials are shown. Patients show greater differences between high- and low-control error rates compared with controls.

Fig. 3.

Frequency–time plots of within- and across-group comparisons of induced γ-band activity. All plots span frequencies 8–80 Hz (y axis), which includes the 30- to 80-Hz range used to define γ activity in the band-specific analyses, over the baseline (−200 to 0 ms), cue (0–500 ms), and delay (500–1,500 ms) periods (x axis). (Left and Center) Statistical comparisons (Wilcoxon signed-rank test) of high- vs. low-control conditions. (Left) Controls. (Center) Patients. (Right) Group comparison of the difference between the high- and low-control conditions (controls vs. patients; Mann–Whitney U test). Shown are negative log P values for all plots. For display purposes, all values represent the statistical comparisons without multiple-comparison corrections. (Upper) Left frontal electrode. (Lower) Right frontal electrode. The frontal scalp map is a summary map of group differences over the delay period, showing locations of the left and right electrodes (circled; the back of the head is not shown because of very minimal activation differences). (Left and Center) Hot colors denote greater γ power for the high- vs. low-control condition, and cool colors show the reverse. (Right) Hot colors denote controls having greater positive differences between the high- and low-control conditions compared with patients, and cool colors show the reverse.

Fig. 4.

Correlation with performance. Shown are accuracy rates for high-control condition for healthy control subjects plotted against late delay γ power for the high-control condition in the right frontal region.