Prefrontal oscillatory slowing in early-course schizophrenia is associated with worse cognitive performance and negative symptoms: a TMS-EEG study.

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.

N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study.

N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho's alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.

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

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.

Examining First Night Effect on Sleep Parameters with hd-EEG in Healthy Individuals.

Difficulty sleeping in a novel environment is a common phenomenon that is often described as the first night effect (FNE). Previous works have found FNE on sleep architecture and sleep power spectra parameters, especially during non-rapid eye movement (NREM) sleep. However, the impact of FNE on sleep parameters, including local differences in electroencephalographic (EEG) activity across nights, has not been systematically assessed. Here, we performed high-density EEG sleep recordings on 27 healthy individuals on two nights and examined differences in sleep architecture, NREM (stages 2 and 3) EEG power spectra, and NREM power topography across nights. We found higher wakefulness after sleep onset (WASO), reduced sleep efficiency, and less deep NREM sleep (stage 3), along with increased high-frequency NREM EEG power during the first night of sleep, corresponding to small to medium effect sizes (Cohen's d ≤ 0.5). Furthermore, study individuals showed significantly lower slow-wave activity in right frontal/prefrontal regions as well as higher sigma and beta activities in medial and left frontal/prefrontal areas, yielding medium to large effect sizes (Cohen's d ≥ 0.5). Altogether, these findings suggest the FNE is characterized by less efficient, more fragmented, shallower sleep that tends to affect especially certain brain regions. The magnitude and specificity of these effects should be considered when designing sleep studies aiming to compare across night effects.