Multimodal Transcranial Magnetic Stimulation Research Articles

Sex differences in mild vascular cognitive impairment: A multimodal transcranial magnetic stimulation study.

Sex differences in vascular cognitive impairment (VCI) at risk for future dementia are still debatable. Transcranial magnetic stimulation (TMS) is used to evaluate cortical excitability and the underlying transmission pathways, although a direct comparison between males and females with mild VCI is lacking. Sixty patients (33 females) underwent clinical, psychopathological, functional, and TMS assessment. Measures of interest consisted of: resting motor threshold, latency of motor evoked potentials (MEPs), contralateral silent period, amplitude ratio, central motor conduction time (CMCT), including the F wave technique (CMCT-F), short-interval intracortical inhibition (SICI), intracortical facilitation, and short-latency afferent inhibition, at different interstimulus intervals (ISIs). Males and females were comparable for age, education, vascular burden, and neuropsychiatric symptoms. Males scored worse at global cognitive tests, executive functioning, and independence scales. MEP latency was significantly longer in males, from both sides, as well CMCT and CMCT-F from the left hemisphere; a lower SICI at ISI of 3 ms from the right hemisphere was also found. After correction for demographic and anthropometric features, the effect of sex remained statistically significant for MEP latency, bilaterally, and for CMCT-F and SICI. The presence of diabetes, MEP latency bilaterally, and both CMCT and CMCT-F from the right hemisphere inversely correlated with executive functioning, whereas TMS did not correlate with vascular burden. We confirm the worse cognitive profile and functional status of males with mild VCI compared to females and first highlight sex-specific changes in intracortical and cortico-spinal excitability to multimodal TMS in this population. This points to some TMS measures as potential markers of cognitive impairment, as well as targets for new drugs and neuromodulation therapies.

Spontaneous Fluctuations in Oscillatory Brain State Cause Differences in Transcranial Magnetic Stimulation Effects Within and Between Individuals.

Transcranial magnetic stimulation (TMS) can cause measurable effects on neural activity and behavioral performance in healthy volunteers. In addition, TMS is increasingly used in clinical practice for treating various neuropsychiatric disorders. Unfortunately, TMS-induced effects show large intra- and inter-subject variability, hindering its reliability, and efficacy. One possible source of this variability may be the spontaneous fluctuations of neuronal oscillations. We present recent studies using multimodal TMS including TMS-EMG (electromyography), TMS-tACS (transcranial alternating current stimulation), and concurrent TMS-EEG-fMRI (electroencephalography, functional magnetic resonance imaging), to evaluate how individual oscillatory brain state affects TMS signal propagation within targeted networks. We demonstrate how the spontaneous oscillatory state at the time of TMS influences both immediate and longer-lasting TMS effects. These findings indicate that at least part of the variability in TMS efficacy may be attributable to the current practice of ignoring (spontaneous) oscillatory fluctuations during TMS. Ignoring this state-dependent spread of activity may cause great individual variability which so far is poorly understood and has proven impossible to control. We therefore also compare two technical solutions to directly account for oscillatory state during TMS, namely, to use (a) tACS to externally control these oscillatory states and then apply TMS at the optimal (controlled) brain state, or (b) oscillatory state-triggered TMS (closed-loop TMS). The described multimodal TMS approaches are paramount for establishing more robust TMS effects, and to allow enhanced control over the individual outcome of TMS interventions aimed at modulating information flow in the brain to achieve desirable changes in cognition, mood, and behavior.

A Review of Studies Leveraging Multimodal TMS-fMRI Applications in the Pathophysiology and Treatment of Schizophrenia.

The current review provides an overview of the existing literature on multimodal transcranial magnetic stimulation, and functional magnetic resonance imaging (TMS/fMRI) studies in individuals with schizophrenia and discusses potential future avenues related to the same. Multimodal studies investigating pathophysiology have explored the role of abnormal thalamic reactivity and have provided further evidence supporting the hypothesis of schizophrenia as a disorder of aberrant connectivity and cortical plasticity. Among studies examining treatment, low-frequency rTMS for the management of persistent auditory verbal hallucinations (AVH) was the most studied. While multimodal TMS/fMRI studies have provided evidence of involvement of local speech-related and distal networks on stimulation of the left temporoparietal cortex, current evidence does not suggest the superiority of fMRI based neuronavigation over conventional methods or of active rTMS over sham for treatment of AVH. Apart from these, preliminary findings suggest a role of rTMS in treating deficits in neurocognition, social cognition, and self-agency. However, most of these studies have only examined medication-resistant symptoms and have methodological concerns arising from small sample sizes and short treatment protocols. That being said, combining TMS with fMRI appears to be a promising approach toward elucidating the pathophysiology of schizophrenia and could also open up a possibility toward developing personalized treatment for its persistent and debilitating symptoms.

P07-S Multimodal TMS has the potential to improve the diagnostic process in epilepsy

Background In epilepsy, a disturbed cortical excitability results in a predisposition to generate seizures. The limited diagnostic sensitivity of the electroencephalogram motivates the search for a novel biomarker. Transcranial magnetic stimulation (TMS) is a technique to assess cortical excitability. We used a multimodal TMS approach to evaluate differences between healthy controls, first seizure patients diagnosed with epilepsy and those without epilepsy. Methods We included twenty-one healthy subjects and twenty-one first seizure patients, of which seven were diagnosed with epilepsy. Both motor cortices were stimulated with 50 single pulses and 50 paired pulses at six interstimulus intervals (ISIs) between 50–300 As single pulse TMS readouts we analyzed amplitudes of the motor evoked potential (MEP) and TMS evoked potential (TEP). For paired pulse stimulation, we assessed long intracortical inhibition (LICI) of the MEP and TEP. Results We found no significant differences in MEP or TEP amplitudes using single pulse TCompared to healthy controls, epilepsy patients showed significantly increased LICI of the N100 and P180 components for ISI 200 Furthermore, we found facilitation at ISI 100 ms in epilepsy patients and inhibition in patients without epilepsy. Conclusions Multimodal TMS has the potential to improve the diagnostic process in epilepsy. Biomarkers include increased LICI at ISI 200 ms and facilitation at ISI 100 At a group level, paired pulse TMS differentiated between healthy controls, patients with epilepsy and patients without epilepsy. To establish the true potential, data of more patients is needed, which may enable analysis at the individual level.

Unilateral cortical hyperexcitability in congenital hydrocephalus: A TMS study

Introduction: Changes in cortical excitability are considered to play an important role in promoting brain plasticity both in healthy people and in neurological diseases. Hydrocephalus is a brain development disorder related to an excessive accumulation of cerebrospinal fluid (CSF) in the ventricular system. The functional relevance of cortical structural changes described in this disease is largely unexplored in human. We investigated cortical excitability using multimodal transcranial magnetic stimulation (TMS) in a case of congenital hydrocephalus with almost no neurological signs. Methods: A caucasian 40 years old, ambidextrous and multilingual woman affected by occult spina bifida and congenital symmetrical hydrocephalous underwent a TMS study. The intracortical and interhemispheric paired pulse paradigms were used, together with the mapping technique. Results: No significant differences were found in the resting motor thresholds between the two hemispheres. Instead, the intracortical excitability curves were statistically different between the two hemispheres (with short intracortical inhibition (SICI) being strongly reduced and intracortical facilitation (ICF) enhanced in the right one), and the interhemispheric curves showed a general hyper-excitability on the right hemisphere (when conditioned by the left one) and a general hypo-excitability in the left hemisphere (when conditioned by the right one). It is noteworthy that an asymmetric right hemisphere (RH) change of excitability was observed by means of mapping technique. Conclusion: We hypothesize that in this ambidextrous subject, the observed RH hyper-excitability could represent a mechanism of plasticity to preserve functionality of specific brain areas possibly devoted to some special skills, such as multilingualism.