Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Sodium valproate in migraine without aura and medication overuse headache: A randomized controlled trial

Objective: To assess the efficacy, safety and tolerability of sodium valproate (800. mg/die) compared with placebo in medication-overuse headache patients with a history of migraine without aura. Methods: This is a multicenter, randomized, double-blind, placebo-controlled study enrolled medication-overuse headache patients for a 3-month treatment period with sodium valproate (800. mg/day) or placebo after a 6 day outpatient detoxification regimen, followed by a 3-month follow-up. Primary outcome was defined by the proportion of patients achieving ≥50% reduction in the number of days with headache per month (responders) from the baseline to the last 4 weeks of the 3-month treatment. Multivariate logistic regression models were used on the primary endpoint, adjusting for age, sex, disease duration, comorbidity and surgery. The last-observation-carried-forward method was used to adjust for missing values. Results: Nine sites enrolled 130 patients and, after a 6-day detoxification phase, randomized 88 eligible patients. The 3-month responder rate was higher in the sodium valproate (45.0%) than in the placebo arm (23.8%) with an absolute difference of about 20% (p=0.0431). Sodium valproate had safety and tolerability profiles comparable to placebo. Conclusions: The present study supports the efficacy and safety of sodium valproate in the treatment of medication overuse headache with history of migraine after detoxification

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study

Background: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. Materials and methods: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. Results: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50–160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220–560 ms; 190–420 ms). Patients showed a reduction of both early (50–110 ms) gamma increase and later (180–230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. Conclusion: Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics

Lack of habituation of evoked visual potentials in analytic information processing style: evidence in healthy subjects.

Habituation is considered one of the most basic mechanisms of learning. Habituation deficit to several sensory stimulations has been defined as a trait of migraine brain and also observed in other disorders. On the other hand, analytic information processing style is characterized by the habit of continually evaluating stimuli and it has been associated with migraine. We investigated a possible correlation between lack of habituation of evoked visual potentials and analytic cognitive style in healthy subjects. According to Sternberg–Wagner self-assessment inventory, 15 healthy volunteers (HV) with high analytic score and 15 HV with high global score were recruited. Both groups underwent visual evoked potentials recordings after psychological evaluation. We observed significant lack of habituation in analytical individuals compared to global group. In conclusion, a reduced habituation of visual evoked potentials has been observed in analytic subjects. Our results suggest that further research should be undertaken regarding the relationship between analytic cognitive style and lack of habituation in both physiological and pathophysiological conditions

A study of migraine characteristics in joint hypermobility syndrome a.k.a. Ehlers-Danlos syndrome, hypermobility type

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients. The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent group comparisons. Results showed that in JHS/EDS-HT: (1) migraine has an earlier onset (12.6 vs 17 years of age; p = 0.005); (2) the rate of migraine days/month is higher (15 vs 9.3 days/month; p = 0.01); (3) accompanying symptoms are usually more frequent; (4) HIT-6 and MIDAS scores are higher (p = 0.04 and p = 0.03); (5) efficacy of rescue medication is almost identical, although, total drug consumption is significantly lower (p < 0.04). Joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type patients have a more severe headache syndrome with respect to the MO group, therefore demonstrating that migraine has a very high impact on quality of life in this disease