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Original Article | ONLINE FIRST

Reduced Natural Oscillatory Frequency of Frontal Thalamocortical Circuits in Schizophrenia

Fabio Ferrarelli, MD, PhD; Simone Sarasso, PhD; Yelena Guller, BS; Brady A. Riedner, PhD; Michael J. Peterson, MD, PhD; Michele Bellesi, MD, PhD; Marcello Massimini, MD, PhD; Bradley R. Postle, PhD; Giulio Tononi, MD, PhD
Arch Gen Psychiatry. 2012;69(8):766-774. doi:10.1001/archgenpsychiatry.2012.147.
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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.

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Figures

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Grahic Jump Location

Figure 1. Patients with schizophrenia showed a reduction in several transcranial magnetic stimulation (TMS)–evoked fast oscillation parameters, including amplitude, duration, and frequency content in frontal cortical areas. The TMS was administered to 4 cortical areas (shown in the 3-dimensional individual magnetic resonance imaging reconstruction), and TMS-evoked electroencephalographic responses were collected for patients with schizophrenia and healthy control subjects (gray traces). The black traces reflect the responses at the electrodes closest to the TMS. Data are shown for a representative subject from each group. Event-related spectral perturbation plots show the TMS-related changes in amplitude and their duration, with dotted lines highlighting the frequency with the highest activity, the natural frequency, for each cortical area.

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Grahic Jump Location

Figure 2. The frequency of transcranial magnetic stimulation–evoked prefrontal oscillations was the most sensitive parameter for identifying patients with schizophrenia and healthy control subjects. A, The individual natural frequency values of healthy control subjects and patients with schizophrenia are shown for 4 cortical areas. Horizontal lines indicate mean natural frequency values of each group for each cortical area. * P < .05; † P < .001. B, The natural frequency at these cortical areas, which are displayed in 3-dimensional magnetic resonance imaging, is shown for each study participant.

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Grahic Jump Location

Figure 3. The frequency of prefrontal cortex oscillations was inversely related to the level of positive symptoms on the Positive and Negative Syndrome Scale (PANSS) (A) as well as to the reaction time of correct responses on a word memory task (B) in patients with schizophrenia.

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