Transcranial Magnetic Stimulation Assessments Research Articles

TMS assessment of corticospinal tract integrity after stroke: broadening the concept to inform neurorehabilitation prescription.

Upper limb actions require intersegmental coordination of the scapula, shoulders, elbows, forearms, wrists, and hand muscles. Stroke hemiparesis, presenting as an impairment of an intersegmentally coordinated voluntary movement, is associated with altered integrity of corticospinal tract (CST) transmission from the motor cortex (M1) to muscles. Motor evoked potentials (MEPs) elicited by M1 transcranial magnetic stimulation (TMS) of "at rest" muscles, or as a backup, during muscle contraction have been used to identify CST integrity and predict the outcome after hemiparesis, under the implicit assumption that MEPs present in only one or two muscles are manifest surrogates of CST integrity for other muscles of the upper limbs. This study presents a method for applying TMS during motor tasks that involve proximal and distal muscles. It focuses on evaluating multi-muscle electromyography (EMG) and MEPs across all task-relevant limb segments. Protocols are presented for assessing voluntary motor behavior in individuals with hemiparetic stroke using isometric, unimanual, bimanual, and "REST" conditions that broaden the concept of the degree of CST integrity in order to inform clinical prescription for neurorehabilitation and distinguish its potential as a prognostic tool. Data describing the recordings of multi-muscle transcranial magnetic stimulation induced motor evoked potentials (TMS-MEP) will be presented in a case of subacute hemiparetic stroke to elucidate our perspective.

Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis

ObjectiveInvestigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability. MethodsParticipants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition. ResultsParticipants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS<3). This resulted in lower E/I ratios in the higher disability group. Individuals with higher disability presented with asymmetrical E/I ratios between brain hemispheres, a pattern not present in the group with lower disability. In regression analyses controlling for demographics, lowered TMS-probed E/I ratio predicted variance in disability (R2 = 0.37, p < 0.001), upper extremity function (R2 = 0.35, p < 0.001), walking speed (R2 = 0.22, p = 0.005), and cognitive performance (R2 = 0.25, p = 0.007). Receiver Operating Characteristic curve analysis confirmed ‘excellent’ discriminative ability of the E/I ratio in distinguishing high and low disability. Finally, excitation superiorly correlated with the E/I ratio than overall inhibition in both hemispheres (p ≤ 0.01). ConclusionThe E/I ratio is a potential neurophysiological biomarker of disability level in MS, especially when assessed in the hemisphere corresponding to the weaker body side. Interventions aimed at increasing cortical excitation or reducing inhibition may restore E/I balance potentially stalling progression or improving function in MS.

No effect of whole-hand water flow stimulation on skill acquisition and retention during sensorimotor adaptation.

Repetitive somatosensory stimulation (RSS) is a conventional approach to modulate the neural states of both the primary somatosensory cortex (S1) and the primary motor cortex (M1). However, the impact of RSS on skill acquisition and retention in sensorimotor adaptation remains debated. This study aimed to investigate whether whole-hand water flow (WF), a unique RSS-induced M1 disinhibition, influences sensorimotor adaptation by examining the hypothesis that whole-hand WF leads to M1 disinhibition; thereby, enhancing motor memory retention. Sixty-eight young healthy participants were randomly allocated to three groups based on the preconditioning received before motor learning: control, whole-hand water immersion (WI), and whole-hand WF. The experimental protocol for all the participants spanned two consecutive days. On the initial day (day 1), baseline transcranial magnetic stimulation (TMS) assessments (T0) were executed before any preconditioning. Subsequently, each group underwent their respective 30 min preconditioning protocol. To ascertain the influence of each preconditioning on the excitability of the M1, subsequent TMS assessments were conducted (T1). Following this, all participants engaged in the motor learning (ML) of a visuomotor tracking task, wherein they were instructed to align a cursor with a target trajectory by modulating the pinch force. Upon completion of the ML session, final TMS assessments (T2) were conducted. All participants were required to perform the same motor learning 24 h later on day 2. The results revealed that whole-hand WF did not significantly influence skill acquisition during sensorimotor adaptation, although it did reduce intracortical inhibition. This phenomenon is consistent with the idea that S1, rather than M1, is involved in skill acquisition during the early stages of sensorimotor adaptation. Moreover, memory retention 24 h after skill acquisition did not differ significantly across the three groups, challenging our initial hypothesis that whole-hand WF enhances memory retention throughout sensorimotor adaptation. This could be due to the inability of whole-hand WF to alter sensorimotor connectivity and integration, as well as the nature of the plastic response elicited by the preconditioning. In conclusion, these findings suggest that although whole-hand WF attenuates intracortical inhibition, it does not modulate skill acquisition or motor memory retention during sensorimotor adaptation.

178 Brains on the Pitch: Investigating the Neurophysiological and Neurocognitive Effects of Repetitive Head Impacts in Adolescent Female Soccer Players During a Single Season

INTRODUCTION: Repetitive exposure to head impact in contact sports has raised concerns for potential long-term structural and functional neurologic effects. This relationship has been minimally explored in female athletes, with conflicting results arising from the limited reports on this topic. METHODS: Prospective cohort design with pre- and post-season assessments of neurocognitive function, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). Neurocognitive battery evaluated processing speed, memory, and executive function domains via computerized (ImPACT) and paper-and-pencil testing. TMS assessments included motor evoked potential onset; interhemispheric conduction times; intercortical and intracortical inhibition. DTI measures included fractional anisotropy (FA) for white matter tracts of interest, including: posterior limb of internal capsule; cortical spinal tract; corpus callosum - selected for common involvement in traumatic brain injury within other studies. RESULTS: One player was officially diagnosed with concussion and was included in analysis. Neurocognitive performance was intact relative to same aged peers, and there were no significant differences over the season based on mean reliable change indices (-0.79-0.93). Paired t-test analysis indicated that the TMS measures were not significantly different between the two timepoints. Furthermore, DTI FA values and TMS measures were not notably different pre- versus postseason. CONCLUSIONS: In this cohort of high school female athletes, we did not observe significant anatomic, physiologic, or functional effects from repetitive head impacts. Our findings contradict previous studies that showed significant neurophysiologic and neurocognitive changes, even in the absence of clinically-observed concussion. Further research is needed to fully understand the long-term consequences of repetitive head impacts in female athletes and to develop effective strategies for mitigating potential risks.

Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

Expression of CD40 and CD192 in Classical Monocytes in Multiple Sclerosis Patients Assessed with Transcranial Magnetic Stimulation.

Expression of CD40 and CD192 markers in different monocyte subpopulations has been reported to be altered in people with MS (pwMS). Also, functional connectivity of the corticospinal motor system pathway alterations has been proved by transcranial magnetic stimulation (TMS). The study objective was to investigate the expression of CD40 and CD192 in classical (CD14++CD16-), intermediate CD14++CD16+ and non-classical (CD14+CD16++) blood monocyte subpopulations in pwMS, undergoing neurophysiological TMS assessment of the corticospinal tract integrity by recording motor-evoked potentials (MEPs). Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing-remitting MS treated with teriflunomide. Then, immunological analysis was conducted on peripheral blood samples collected from the patients and 10 healthy controls (HC). The blood samples were incubated with anti-human CD14, CD16, CD40 and CD192 antibodies. Next, pwMS underwent neurological testing of functional disability (EDSS) and TMS assessment with recording MEPs from upper and lower extremity muscles. The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40's pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.

Motor Cortex Inhibition and Facilitation Correlates with Fibromyalgia Compensatory Mechanisms and Pain: A Cross-Sectional Study.

The role of transcranial magnetic stimulation (TMS) measures as biomarkers of fibromyalgia syndrome (FMS) phenotypes is still unclear. We aimed to determine the clinical correlates of TMS measures in FMS patients. We conducted a cross-sectional analysis that included 58 patients. We performed standardized TMS assessments, including resting motor threshold (MT), motor-evoked potential (MEP), short intracortical inhibition (SICI), and intracortical facilitation (ICF). Sociodemographic, clinical questionnaires, and quantitative sensory testing were collected from all of the patients. Univariate and multivariate linear regression models were built to explore TMS-associated factors. We found that SICI did not significantly correlate with pain levels but was associated with sleepiness, comorbidities, disease duration, and anxiety. On the other hand, ICF showed a positive correlation with pain levels and a negative correlation with body mass index (BMI). BMI was a negative effect modifier of the ICF and pain association. The clinical correlates of MT and MEP were scarce. Our results suggest that SICI and ICF metrics are potential phenotyping biomarkers in FMS related to disease compensation and levels of pain perception, respectively. The clinical translation of TMS paired-pulse protocols represents an opportunity for a mechanistic understanding of FMS and the future development of precision treatments.

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.

Clinical application of transcranial magnetic stimulation in multiple sclerosis.

Multiple sclerosis (MS) is a common chronic, autoimmune-mediated inflammatory and neurodegenerative disease of the central nervous system. The treatment of MS has enormous progress with disease-modifying drugs, but the complexity of the disease course and the clinical symptoms of MS requires personalized treatment and disease management, including non-pharmacological treatment. Transcranial magnetic stimulation (TMS) is a painless and non-invasive brain stimulation technique, which has been widely used in neurological diseases. In this review, we mainly focus on the progress of physiological assessment and treatment of TMS in MS.

Motor Cortical Network Flexibility is Associated With Biomechanical Walking Impairment in Chronic Stroke

Background: The inability to flexibly modulate motor behavior with changes in task demand or environmental context is a pervasive feature of motor impairment and dysfunctional mobility after stroke. Objective: The purpose of this study was to test the reactive and modulatory capacity of lower-limb primary motor cortical (M1) networks using electroencephalography (EEG) measures of cortical activity evoked by transcranial magnetic stimulation (TMS) and to evaluate their associations with clinical and biomechanical measures of walking function in chronic stroke. Methods: TMS assessments of motor cortex excitability were performed during rest and active ipsilateral plantarflexion in chronic stroke and age-matched controls. TMS-evoked motor cortical network interactions were quantified with simultaneous EEG as the post-TMS (0–300 ms) beta (15–30 Hz) coherence between electrodes overlying M1 bilaterally. We compared TMS-evoked coherence between groups during rest and active conditions and tested associations with poststroke motor impairment, paretic propulsive gait deficits, and the presence of paretic leg motor evoked potentials (MEPs). Results: Stroke (n = 14, 66 ± 9 years, F = 4) showed lower TMS-evoked cortical coherence and activity-dependent modulation compared to controls (n = 9, 68 ± 6 years, F = 3). Blunted reactivity and atypical modulation of TMS-evoked coherence were associated with lower paretic ankle moments for propulsive force generation during walking and absent paretic MEPs. Conclusions: Impaired flexibility of motor cortical networks to react to TMS and modulate during motor activity is distinctly associated with paretic limb biomechanical walking impairment, and may provide useful insight into the neuromechanistic underpinnings of chronic post-stroke mobility deficits.

Standing Neurophysiological Assessment of Lower Extremity Muscles Post-Stroke.

Transcranial magnetic stimulation (TMS) is a common tool used to measure the behavior of motor circuits in healthy and neurologically impaired populations. TMS is used extensively to study motor control and the response to neurorehabilitation of the upper extremities. However, TMS has been less utilized in the study of lower extremity postural and walking-specific motor control. The limited use and the additional methodological challenges of lower extremity TMS assessments have contributed to the lack of consistency in lower extremity TMS procedures within the literature. Inspired by the decreased ability to record lower extremity TMS motor evoked potentials (MEP), this methodological report details steps to enable post-stroke TMS assessments in a standing posture. The standing posture allows for the activation of the neuromuscular system, reflecting a state more akin to the system's state during postural and walking tasks. Using dual-top force plates, we instructed participants to equally distribute their weight between their paretic and non-paretic legs. Visual feedback of the participants' weight distribution was provided. Using image guidance software, we delivered single TMS pulses via a double-cone coil to the participants' lesioned and non-lesioned hemispheres and measured the corticomotor response of the paretic and non-paretic tibialis anterior and soleus muscles. Performing assessments in the standing position increased the TMS response rate and allowed for the use of the lower stimulation intensities compared to the standard sitting/resting position. Utilization of this TMS protocol can provide a common approach to assess the lower extremity corticomotor response post-stroke when the neurorehabilitation of postural and gait impairments are of interest.

The Signature of Primary Writing Tremor Is Dystonic.

It has been debated for decades whether primary writing tremor is a form of dystonic tremor, a variant of essential tremor, or a separate entity. We wished to test the hypothesis that primary writing tremor and dystonia share a common pathophysiology. The objective of the present study was to investigate the pathophysiological hallmarks of dystonia in patients affected by primary writing tremor. Ten patients with idiopathic dystonic tremor syndrome, 7 with primary writing tremor, 10 with essential tremor, and 10 healthy subjects were recruited. They underwent eyeblink classic conditioning, blink recovery cycle, and transcranial magnetic stimulation assessment, including motor-evoked potentials and short- and long-interval intracortical inhibition at baseline. Transcranial magnetic stimulation measures were also recorded after paired-associative plasticity protocol. Primary writing tremor and dystonic tremor syndrome had a similar pattern of electrophysiological abnormalities, consisting of reduced eyeblink classic conditioning learning, reduced blink recovery cycle inhibition, and a lack of effect of paired-associative plasticity on long-interval intracortical inhibition. The latter 2 differ from those obtained in essential tremor and healthy subjects. Although not significant, slightly reduced short-interval intracortical inhibition and a larger effect of paired-associative plasticity in primary writing tremor and dystonic tremor syndrome, compared with essential tremor and healthy subjects, was observed. Our initial hypothesis of a common pathophysiology between dystonia and primary writing tremor has been confirmed. Primary writing tremor might be considered a form of dystonic tremor. © 2021 International Parkinson and Movement Disorder Society.

Reliability of corticospinal excitability estimates for the vastus lateralis: Practical considerations for lower limb TMS task selection

Transcranial magnetic stimulation (TMS) is increasingly used to examine lower extremity corticospinal excitability (CSE) in clinical and sports research. Because CSE is task-specific, there is growing emphasis on the use of ecological tasks. Nevertheless, the comparative reliability of CSE measurements during established (e.g. knee extensions; KE) and more recent ecological (e.g. squats; SQT) lower extremity tasks has received less attention. The aim of this study was to compare the test–retest reliability of CSE, force, and muscle activity (EMG) during isometric SQT and KE. 19 right-footed men (age: 25 ± 5 yrs) with similar fitness and body composition performed SQT (N = 7) or KE (N = 12) on two consecutive days. Force and EMG were recorded during maximum voluntary isometric contractions (MVC). Corticospinal excitability was determined in the dominant leg during light (15% MVC) contractions based on motor evoked potential (MEP) stimulus–response-curves (SRC). Test-retest reliability, absolute agreement, and consistency were determined for force, EMG, and SRC MEP maximum (MEPMAX) and rising phase midpoint (V50). As a secondary analysis, all outcomes were compared between groups with mixed-methods ANCOVAs (Task × Time, covariate: body-fat-percentage). Compared with SQT, KE displayed better test–retest reliability and agreement for MEPMAX whereas V50, force, and EMG were similarly reliable. Force (p = 0.01) and MEPMAX (p = 0.02) were also greater during KE despite a similar V50 (p = 0.11). Differences in test–retest reliability, absolute agreement, and between-group comparisons highlight the need to carefully select lower limb TMS assessment tasks and encourage future efforts to balance ecological validity with statistical sensitivity.

Classification accuracy of TMS for the diagnosis of mild cognitive impairment

ObjectiveTo evaluate the performance of a Random Forest (RF) classifier on Transcranial Magnetic Stimulation (TMS) measures in patients with Mild Cognitive Impairment (MCI). MethodsWe applied a RF classifier on TMS measures obtained from a multicenter cohort of patients with MCI, including MCI-Alzheimer’s Disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), and healthy controls (HC). All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The primary outcome measures were the classification accuracy, precision, recall and F1-score of TMS in differentiating each disorder. Results160 participants were included, namely 64 patients diagnosed as MCI-AD, 28 as MCI-FTD, 14 as MCI-DLB, and 47 as healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.72 to 0.86), high precision (0.72–0.90), high recall (0.75–0.98), and high F1-scores (0.78–0.92), in differentiating each neurodegenerative disorder. By computing a new classifier, trained and validated on the current cohort of MCI patients, classification indices showed even higher accuracy (ranging from 0.83 to 0.93), precision (0.87–0.89), recall (0.83–1.00), and F1-scores (0.85–0.94). ConclusionsTMS may be considered a useful additional screening tool to be used in clinical practice in the prodromal stages of neurodegenerative dementias.

Integration of Convergent Sensorimotor Inputs Within Spinal Reflex Circuits in Healthy Adults

The output from motor neuron pools is influenced by the integration of synaptic inputs originating from descending corticomotor and spinal reflex pathways. In this study, using paired non-invasive brain and peripheral nerve stimulation, we investigated how descending corticomotor pathways influence the physiologic recruitment order of the soleus Hoffmann (H-) reflex. Eleven neurologically unimpaired adults (9 females; mean age 25 ± 3 years) completed an assessment of transcranial magnetic stimulation (TMS)-conditioning of the soleus H-reflex over a range of peripheral nerve stimulation (PNS) intensities. Unconditioned H-reflex recruitment curves were obtained by delivering PNS pulses to the posterior tibial nerve. Subsequently, TMS-conditioned H-reflex recruitment curves were obtained by pairing PNS with subthreshold TMS at short (−1.5 ms) and long (+10 ms) intervals. We evaluated unconditioned and TMS-conditioned H-reflex amplitudes along the ascending limb, peak, and descending limb of the H-reflex recruitment curve. Our results revealed that, for long-interval facilitation, TMS-conditioned H-reflex amplitudes were significantly larger than unconditioned H-reflex amplitudes along the ascending limb and peak of the H-reflex recruitment curve. Additionally, significantly lower PNS intensities were needed to elicit peak H-reflex amplitude (Hmax) for long-interval facilitation compared to unconditioned. These findings suggest that the influence of descending corticomotor pathways, particularly those mediating long-interval facilitation, contribute to changing the recruitment gain of the motor neuron pool, and can inform future methodological protocols for TMS-conditioning of H-reflexes. By characterizing and inducing short-term plasticity in circuitry mediating short- and long-interval TMS-conditioning of H-reflex amplitudes, future studies can investigate supraspinal and spinal circuit contributions to abnormal motor control, as well as develop novel therapeutic targets for neuromodulation.

On the Use of TMS to Investigate the Pathophysiology of Neurodegenerative Diseases.

Neurodegenerative diseases are a collection of disorders that result in the progressive degeneration and death of neurons. They are clinically heterogenous and can present as deficits in movement, cognition, executive function, memory, visuospatial awareness and language. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that allows for the assessment of cortical function in vivo. We review how TMS has been used for the investigation of three neurodegenerative diseases that differ in their neuroanatomical axes: (1) Motor cortex—corticospinal tract (motor neuron diseases), (2) Non-motor cortical areas (dementias), and (3) Subcortical structures (parkinsonisms). We also make four recommendations that we hope will benefit the use of TMS in neurodegenerative diseases. Firstly, TMS has traditionally been limited by the lack of an objective output and so has been confined to stimulation of the motor cortex; this limitation can be overcome by the use of concurrent neuroimaging methods such as EEG. Given that neurodegenerative diseases progress over time, TMS measures should aim to track longitudinal changes, especially when the aim of the study is to look at disease progression and symptomatology. The lack of gold-standard diagnostic confirmation undermines the validity of findings in clinical populations. Consequently, diagnostic certainty should be maximized through a variety of methods including multiple, independent clinical assessments, imaging and fluids biomarkers, and post-mortem pathological confirmation where possible. There is great interest in understanding the mechanisms by which symptoms arise in neurodegenerative disorders. However, TMS assessments in patients are usually carried out during resting conditions, when the brain network engaged during these symptoms is not expressed. Rather, a context-appropriate form of TMS would be more suitable in probing the physiology driving clinical symptoms. In all, we hope that the recommendations made here will help to further understand the pathophysiology of neurodegenerative diseases.

Obstructive Sleep Apnea Syndrome: A Preliminary Navigated Transcranial Magnetic Stimulation Study.

PurposeAn increase in resting motor threshold (RMT), prolonged cortical silent period duration (CSP), and reduced short-latency afferent inhibition (SAI), confirmed with previous transcranial magnetic stimulation (TMS), suggest decreased cortical excitability in obstructive sleep apnea syndrome (OSAS). The present study included MRI of OSAS patients for navigated TMS assessment of the RMT, as an index of the threshold for corticospinal activation at rest, and SAI as an index of cholinergic neurotransmission. We hypothesize to confirm findings on SAI and RMT with adding precision in the targeting of motor cortex in OSAS.Subjects and MethodsAfter acquiring head MRIs for 17 severe right-handed OSAS and 12 healthy subjects, the motor cortex was mapped with nTMS to assess the RMT and SAI, with motor evoked potentials (MEPs) recorded from the abductor-pollicis brevis (APB) muscle. The 120%RMT intensity was used for the SAI by a paired-pulse paradigm in which the electrical stimulation to the median nerve is followed by magnetic stimulation of the motor cortex at inter-stimulus intervals (ISIs) of 18–28 ms (ISIs18-28). The SAI control condition included a recording of MEPs without peripheral stimulation. Latency and amplitude of MEP at RMT at 120%RMT for eleven different at ISIs18-28 were analyzed.ResultsThe study showed a significantly lower percentage deviation of MEP amplitude at ISIs(18-28ms) from the control condition between OSAS and healthy subjects (U=44.0, p=0.01). The intensity of stimulation at RMT was significantly higher in OSAS subjects (U=55.0, p=0.04*). Correlation analysis showed that BMI significantly negatively correlated (ρ=−0.47) with MEP amplitude percentage deviation in OSAS patients.ConclusionThe nTMS study results in increased RMT, and reduced cortical afferent inhibition in OSAS patients for SAI at ISIs18-28, confirming previous findings of impaired cortical afferent inhibition in OSAS. Future nTMS studies are desirable to elucidate the role of RMT and SAI in diagnostics and treatment of OSAS, and to elucidate the usefulness of nTMS in OSAS research.

Classification Accuracy of Transcranial Magnetic Stimulation for the Diagnosis of Neurodegenerative Dementias.

Transcranial magnetic stimulation (TMS) has been suggested as a reliable, noninvasive, and inexpensive tool for the diagnosis of neurodegenerative dementias. In this study, we assessed the classification performance of TMS parameters in the differential diagnosis of common neurodegenerative disorders, including Alzheimer disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). We performed a multicenter study enrolling patients referred to 4 dementia centers in Italy, in accordance with the Standards for Reporting of Diagnostic Accuracy. All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The investigators who performed the index test were masked to the results of the reference test and all other investigations. We trained and tested a random forest classifier using 5-fold cross-validation. The primary outcome measures were the classification accuracy, precision, recall, and F1 score of TMS in differentiating each neurodegenerative disorder. A total of 694 participants were included, namely 273 patients diagnosed as AD, 67 as DLB, and 207 as FTD, and 147 healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.89 to 0.92), high precision (0.86-0.92), high recall (0.93-0.98), and high F1 scores (0.89-0.95) in differentiating each neurodegenerative disorder. TMS is a noninvasive procedure that reliably and selectively distinguishes AD, DLB, FTD, and HC, representing a useful additional screening tool to be used in clinical practice. Ann Neurol 2020;87:394-404.

Safety and Feasibility of Transcranial Magnetic Stimulation as an Exploratory Assessment of Corticospinal Connectivity in Infants After Perinatal Brain Injury: An Observational Study.

Perinatal brain injuries often impact the corticospinal system, leading to motor impairment and cerebral palsy. Although transcranial magnetic stimulation (TMS) has been widely used to study corticospinal connectivity in adults and older children, similar studies of young infants are limited. The objective was to establish the safety and feasibility of advanced TMS assessments of the corticospinal connectivity of young infants with perinatal brain injury. This was a pilot, cross-sectional study of 3- to 12-month-old (corrected age) infants with perinatal stroke or intracranial hemorrhage. Six participants (2 term, 4 preterm) were assessed with stereotactic neuronavigation-guided TMS. Single-pulse TMS was applied to each hemisphere and responses were recorded simultaneously from both upper limbs. During data collection, vital signs and stress responses were measured to assess safety. Developmental motor outcomes were evaluated using the General Movements Assessment and Bayley Scales of Infant and Toddler Development (3rd edition). A clinical diagnosis of cerebral palsy was recorded, if available. No adverse events occurred during TMS testing. All sessions were well tolerated. Contralateral motor evoked responses were detected in 4 of 6 participants. Both contralateral and ipsilateral responses were observed in 2 of 6 participants. TMS responses were not obtained in all participants. This could be related to the location of brain injury or developmental stage of the corticospinal system controlling the wrist flexor muscle group from which responses were recorded. This study provides a summary of the framework for performing novel TMS assessments in infants with perinatal brain injury. Implementing this approach to measure corticospinal connectivity in hypothesis-driven studies in young infants appears to be justified. Such studies could inform the characterization of corticospinal development and the neural mechanisms driving recovery following early interventions.

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.