Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia

Abstract

Objective: Deficits in sensory gating are a common feature of schizophrenia. Failure of inhibitory gating mechanisms, shown by poor suppression of evoked responses to repeated auditory stimuli, has been previously studied using EEG methods. These methods yield information about the temporal characteristics of sensory gating deficits, but do not identify brain regions involved in the process. Hence, the neuroanatomical substrates of poor sensory gating in schizophrenia remain largely unknown. This study used functional magnetic resonance imaging (fMRI) to investigate the functional neuroanatomy of sensory gating deficits in schizophrenia.

Methods: Twelve patients with schizophrenia and 12 healthy comparison subjects were scanned at 3 Tesla while performing a sensory gating task developed for fMRI. P50 EEG evoked potential recordings from a paired-stimulus conditioning-test paradigm were obtained from the same subjects.

Results: Compared to healthy comparison subjects, patients with schizophrenia exhibited greater activation in the hippocampus, thalamus, and dorsolateral prefrontal cortex (DLPFC) during the fMRI sensory gating task. No group difference was observed in the superior temporal gyrus. Schizophrenia subjects also showed decreased P50 suppression as measured with EEG. Hemodynamic response in the fMRI measure was positively correlated with test/conditioning ratios from the EEG sensory gating measure.

Conclusions: Poor sensory gating in schizophrenia is associated with dysfunction of an apparent network of brain regions, including the hippocampus, thalamus and DLPFC. Greater activation of these regions is consistent with evidence for diminished inhibitory function in schizophrenia.

Figure 1

Schematic representation of experimental design. For all conditions, two seconds of scanning was followed by 6 s of silence for inhibitory circuitry to resent. Following the silent period, subjects were presented with a single click, repeated clicks each separated by 500ms, or silence.

Figure 2

Increased hemodynamic response in subjects with schizophrenia (N=12) relative to healthy comparison subjects (N=12) during sensory gating. Statistical parametric maps thresholded at P < 0.01, overlaid onto the average T1-weighted anatomy of all subjects. Local maxima located at x = -24, y = -18, z = -15 (left hippocampus), x = -9, y = -12, z = 3 (left thalamus), x = 9, y = -21, z = 3 (right thalamus), x = -48, y = 36, z = 27 (left DLPFC). Graphs below show mean blood oxygenation level dependent (BOLD) responses in terms of % signal change, relative to the global mean, for the sensory gating measure, (repeated clicks – single click), and for each condition separately, compared to silence. Error bars indicate standard deviations.

Figure 3

Activation across groups of bilateral primary auditory cortex in response to single click (N=24). Statistical parametric maps thresholded at P < 0.01, overlaid onto the average T1-weighted anatomy of all subjects. Local maxima located at x = -42, y = -33, z = -12 (left Heschl's gyrus), x = 42, y = -30, z = 12 (right Heschle's gryus)

Figure 4

P50 sensory gating ratios in schizophrenia subjects (N=11) and healthy comparison subjects (N=11).

Figure 5

Correlations between P50 sensory gating ratios and hemodynamic response during fMRI sensory gating task in the thalamus, hippocampus and DLPFC.