RESUMO
BACKGROUND: Abnormalities in dorsolateral prefrontal cortex (DLPFC) oscillations are neurophysiological signatures of schizophrenia thought to underlie its cognitive deficits. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a measure of cortical oscillations unaffected by sensory relay functionality and/or patients' level of engagement, which are important confounding factors in schizophrenia. Previous TMS-EEG work showed reduced fast, gamma-range oscillations and a slowing of the main DLPFC oscillatory frequency, or natural frequency, in chronic schizophrenia. However, it is unclear whether this DLPFC natural frequency slowing is present in early-course schizophrenia (EC-SCZ) and is associated with symptom severity and cognitive dysfunction. METHODS: We applied TMS-EEG to the left DLPFC in 30 EC-SCZ and 28 healthy control (HC) subjects. Goal-directed working memory performance was assessed using the "AX" Continuous Performance Task (AX-CPT). The EEG frequency with the highest cumulative power at the stimulation site, or natural frequency, was extracted. We also calculated the local Relative Spectral Power (RSP) as the average power in each frequency band divided by the broadband power. RESULTS: Compared to HC, EC-SCZ had reduced DLPFC natural frequency (p=0.0000002, Cohen's d=-2.32) and higher DLPFC beta-range RSP (p=0.0003, Cohen's d=0.77). In EC-SCZ, the DLPFC natural frequency was inversely associated with negative symptoms. Across all participants, the beta-band RSP negatively correlated with the AX-CPT performance. CONCLUSIONS: A DLPFC oscillatory slowing is an early pathophysiological biomarker of schizophrenia that is associated with its symptom severity and cognitive impairments. Future work should assess whether non-invasive neurostimulation can ameliorate prefrontal oscillatory deficits and related clinical functions in EC-SCZ.
RESUMO
Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.