Shared reduction of oscillatory natural frequencies in bipolar disorder, major depressive disorder and schizophrenia.

INTRODUCTION: Recent studies have demonstrated that cortical brain areas tend to oscillate at a specific natural frequency when directly perturbed by transcranial magnetic stimulation (TMS). Fast electroencephalographic (EEG) oscillations, which typically originate from frontal regions, have been reported to be markedly reduced in schizophrenia. METHODS: Here we employed TMS/EEG to assess the natural frequency of the premotor area in a sample of 48 age-matched participants (12 each in major depression disorder (MDD)), bipolar disorder (BPD), schizophrenia (SCZ) and healthy controls. Event related spectral perturbations (ERSP) were obtained for each study participant using wavelet decomposition. RESULTS: TMS resulted in a significant activation of the beta/gamma band response (21-50 Hz) to frontal cortical perturbation in healthy control subjects. By contrast, the main frequencies of frontal EEG responses to TMS were significantly reduced in patients with BPD, MDD and SCZ (11-27 Hz) relative to healthy subjects. CONCLUSIONS: Patients with bipolar disorder, major depression and schizophrenia showed a significantly lower natural frequency of frontal cortico-thalamocortical circuits compared to healthy controls. These results suggest a common neurobiological mechanism of corticothalamic impairment. The most likely candidates include dysfunction of GABAergic circuits. LIMITATIONS: Further studies are needed to consider other biological markers, gene variants, and their interaction with clinical variables.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

BACKGROUND: It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. METHODS: We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. RESULTS: Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. CONCLUSIONS: Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms.

Transcranial magnetic stimulation combined with high-density EEG in altered states of consciousness.

BACKGROUND: This review discusses the advantages of transcranial magnetic stimulation combined with high-density electroencephalography (TMS-hdEEG) over other current techniques of brain imaging. METHODS AND RESULTS: Its application was reviewed, focusing particularly on disorders of consciousness, in the perspective of recent theories of consciousness. Assessment of non-communicative patients with disorders of consciousness remains a clinical challenge and objective measures of the level of consciousness are still needed. Current theories suggest that a key requirement for consciousness is the brain's capacity to rapidly integrate information across different specialized cortical areas. TMS-EEG allows the stimulation of any given cortical area and the recording of the immediate electrical cortical response. This technique has recently been successfully employed to measure changes in brain complexity under physiological, pharmacological and pathological conditions. CONCLUSIONS: This suggests that TMS-EEG is a reliable tool to discriminate between conscious and unconscious patients at the single subject level. Future works are needed to validate and implement this technique as a clinical tool.

Human cortical excitability increases with time awake.

Prolonged wakefulness is associated not only with obvious changes in the way we feel and perform but also with well-known clinical effects, such as increased susceptibility to seizures, to hallucinations, and relief of depressive symptoms. These clinical effects suggest that prolonged wakefulness may be associated with significant changes in the state of cortical circuits. While recent animal experiments have reported a progressive increase of cortical excitability with time awake, no conclusive evidence could be gathered in humans. In this study, we combine transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to monitor cortical excitability in healthy individuals as a function of time awake. We observed that the excitability of the human frontal cortex, measured as the immediate (0-20 ms) EEG reaction to TMS, progressively increases with time awake, from morning to evening and after one night of total sleep deprivation, and that it decreases after recovery sleep. By continuously monitoring vigilance, we also found that this modulation in cortical responsiveness is tonic and not attributable to transient fluctuations of the level of arousal. The present results provide noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep.

Assessing the effects of electroconvulsive therapy on cortical excitability by means of transcranial magnetic stimulation and electroencephalography.

Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resistant patients with severe major depression. Animal studies have demonstrated that electroconvulsive seizures produce potentiation-like synaptic remodeling in both sub-cortical and frontal cortical circuits. However, the electrophysiological effects of ECT in the human brain are not known. In this work, we evaluated whether ECT induces a measurable change in the excitability of frontal cortical circuits in humans. Electroencephalographic (EEG) potentials evoked by transcranial magnetic stimulation (TMS) were collected before and after a course of ECT in eight patients with severe major depression. Cortical excitability was measured from the early and local EEG response to TMS. Clinical assessment confirmed the beneficial effects of ECT on depressive symptoms at the group level. TMS/EEG measurements revealed a clear-cut increase of frontal cortical excitability after ECT as compared to baseline, that was significant in each and every patient. The present findings corroborate in humans the idea that ECT may produce synaptic potentiation, as previously observed in animal studies. Moreover, results suggest that TMS/EEG may be employed in depressed patients to monitor longitudinally the electrophysiological effects of different therapeutic neuromodulators, e.g. ECT, repetitive TMS, and sleep deprivation. To the extent that depression involves an alteration of frontal cortical excitability, these measurements may be used to guide and evaluate treatment progression over time at the single-patient level.