Natural Oscillatory Frequency Slowing in the Premotor Cortex of Early-Course Schizophrenia Patients: A TMS-EEG Study

Abstract

Despite the heavy burden of schizophrenia, research on biomarkers associated with its early course is still ongoing. Single-pulse Transcranial Magnetic Stimulation coupled with electroencephalography (TMS-EEG) has revealed that the main oscillatory frequency (or “natural frequency”) is reduced in several frontal brain areas, including the premotor cortex, of chronic patients with schizophrenia. However, no study has explored the natural frequency at the beginning of illness. Here, we used TMS-EEG to probe the intrinsic oscillatory properties of the left premotor cortex in early-course schizophrenia patients (<2 years from onset) and age/gender-matched healthy comparison subjects (HCs). State-of-the-art real-time monitoring of EEG responses to TMS and noise-masking procedures were employed to ensure data quality. We found that the natural frequency of the premotor cortex was significantly reduced in early-course schizophrenia compared to HCs. No correlation was found between the natural frequency and age, clinical symptom severity, or dose of antipsychotic medications at the time of TMS-EEG. This finding extends to early-course schizophrenia previous evidence in chronic patients and supports the hypothesis of a deficit in frontal cortical synchronization as a core mechanism underlying this disorder. Future work should further explore the putative role of frontal natural frequencies as early pathophysiological biomarkers for schizophrenia.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram

“…The ERSP allows identifying the changes in power as a function of time and frequency, and RSP provides specific normalized information about the distribution of power across frequency bands. Inter-trial coherence (ITC) was extracted as a measure of phase synchronization. Time-frequency maps were extracted between 8 and 45 Hz using Morlet wavelets with 3.5 cycles as implemented in the EEGLAB toolbox and previously reported [12,16,45]. ERSP was computed from the time-frequency maps as the ratio of the spectral power of individual EEG trials relative to the pre-stimulus period [13,45]. The significance of ERSP maps with respect to the baseline was assessed by bootstrapping samples from the pre-stimulus period (500 permutations, two-sided comparison, p-value < 0.05 after False Discovery Rate (FDR) correction for multiple comparisons).…”

Repetitive transcranial magnetic stimulation to the motor cortex leads to a sequential increase in phase synchronization and power of TMS-evoked electroencephalographic recordings

“…Time-frequency maps were extracted between 8 and 45 Hz using Morlet wavelets with 3.5 cycles, as implemented in the EEGLAB toolbox and previously reported [31]. The following TMS- evoked EEG parameters were extracted in the time-frequency domain: Event-related spectral perturbation (ERSP) was calculated to quantify power amplitudes in the frequency domain.…”

“…For M1 stimulation, C1, C3, Cp3, Cp1 electrodes were selected, likewise for DLPFC (AF3, F3, F1, FC3, FC1), ACC (FCz, Cz, FC1, FC2, C1, C2), and PSI (FC7, F C3, C7, C5, C3). Time-frequency maps were extracted between 8 and 45 Hz using Morlet wavelets with 3.5 cycles, as implemented in the EEGLAB toolbox and previously reported [31]. The following TMSevoked EEG parameters were extracted in the time-frequency domain:…”

“…ERSP was computed from the time-frequency maps as the average spectral power ratio of individual EEG trials relative to the pre-stimulus period (-600 to -50 ms). ERSP allows the identification of the changes in power as a function of time and frequency [9,31]. The significance of ERSP maps with respect to the baseline was assessed by bootstrapping samples from the pre-stimulus period (500 permutations, two-sided comparison, p-value < 0.05 after false discovery rate (FDR) correction for multiple comparisons).…”

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram

“…Time‐frequency maps were extracted between 8 and 45 Hz using Morlet wavelets with 3.5 cycles as implemented in the EEGLAB toolbox and previously reported (Donati et al, 2021 ; Ferrarelli et al, 2012 ; Rosanova et al, 2009 ). ERSP was computed from the time‐frequency maps as the ratio of the spectral power of individual EEG trials relative to the pre‐stimulus period (Donati et al, 2023 ; Rosanova et al, 2009 ). The significance of ERSP maps with respect to the baseline was assessed by bootstrapping samples from the pre‐stimulus period (500 permutations, two‐sided comparison, p ‐value < .05 after false discovery rate (FDR) correction for multiple comparisons).…”