Reduced natural oscillatory frequency of frontal thalamocortical circuits in schizophrenia

CONTEXT: Converging evidence from electrophysiological studies suggests that in individuals with schizophrenia, electroencephalographic frontal fast oscillations are reduced. It is still unclear whether this reduction reflects an intrinsic deficit of underlying cortical/thalamocortical circuits and whether this deficit is specific for frontal regions. Recent electrophysiological studies in healthy individuals have established that, when perturbed, different brain regions oscillate at a specific, intrinsically generated dominant frequency, the natural frequency. OBJECTIVE: To assess the natural frequency of the posterior parietal, motor, premotor, and prefrontal cortices in patients with schizophrenia and healthy control subjects. DESIGN: High-density electroencephalographic recordings during transcranial magnetic stimulation of 4 cortical areas were performed. Several transcranial magnetic stimulation–evoked electroencephalographic oscillation parameters, including synchronization, amplitude, and natural frequency, were compared across the schizophrenia and healthy control groups. SETTING: Wisconsin Psychiatric Institute and Clinic, University of Wisconsin–Madison. PARTICIPANTS: Twenty patients with schizophrenia and 20 age-matched healthy control subjects. MAIN OUTCOME MEASURES: High-density electroencephalographic measurements of transcranial magnetic stimulation–evoked activity in 4 cortical areas, scores on the Positive and Negative Syndrome Scale, and performance scores (reaction time, accuracy) on 2 computerized tasks (word memory [Penn Word Recognition Test] and facial memory [Penn Facial Memory Test]). RESULTS: Patients with schizophrenia showed a slowing in the natural frequency of the frontal/prefrontal regions compared with healthy control subjects (from an average of a 2-Hz decrease for the motor area to an almost 10-Hz decrease for the prefrontal cortex). The prefrontal natural frequency of individuals with schizophrenia was slower than in any healthy comparison subject and correlated with both positive Positive and Negative Syndrome Scale scores and reaction time on the Penn Word Recognition Test. CONCLUSIONS: These findings suggest that patients with schizophrenia have an intrinsic slowing in the natural frequency of frontal cortical/thalamocortical circuits, that this slowing is not present in parietal areas, and that the prefrontal natural frequency can predict some of the symptoms as well as the cognitive dysfunctions of schizophrenia.