Higher Resting Motor Threshold Research Articles

Corticospinal excitability across lower limb muscles in humans.

Electrophysiological studies in nonhuman primates reported the existence of strong corticospinal output from the primary motor cortex to distal compared with proximal hindlimb muscles. The extent to which corticospinal output differs across muscles in the leg in humans remains poorly understood. Using transcranial magnetic stimulation over the leg representation of the primary motor cortex, we constructed motor evoked potential (MEP) recruitment curves to measure the resting motor threshold (RMT), maximum MEP amplitude (MEP-max), and slope in the biceps femoris, rectus femoris, tibialis anterior, soleus, and a foot muscle (i.e., abductor hallucis) in intact humans. We found that the RMT was lower and the MEP-max and slope were larger in the abductor hallucis compared with most other muscles tested. In contrast, the RMT was higher and the MEP-max and slope were lower in the biceps femoris compared to all other muscles tested. Corticospinal responses in the rectus femoris, tibialis anterior, and soleus were in between those obtained from other leg muscles, with the soleus having a higher RMT and lower MEP-max and slope than the rectus femoris and tibialis anterior. To examine the origin of increases in corticospinal excitability in the abductor hallucis, we compared short-interval intracortical inhibition (SICI) and F-waves between the abductor hallucis and tibialis anterior. SICI was similar across muscles while the F-wave amplitude was larger in the abductor hallucis compared with the tibialis anterior. These results support a nonuniform distribution of corticospinal output to leg muscles, highlighting that increases in corticospinal excitability in a foot muscle could be related to a spinal origin.NEW & NOTEWORTHY We provide evidence on how corticospinal output differs across muscles in the leg in intact humans. We found that corticospinal responses were larger in a distal intrinsic foot muscle and were smaller in the biceps femoris compared to all other muscles in the leg. Increases in corticospinal excitability to an intrinsic foot muscle could have a spinal origin.

Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review.

Repetitive transcranial magnetic stimulation (rTMS) is widely utilized as an effective treatment for major depressive disorder (MDD) with varying response rates. Factors associated with better treatment outcome remain scarce. This naturalistic retrospective chart review hopes to shed light on easily obtainable and measurable predictive factors for patients referred to rTMS. Protocol parameters, medication, rated scales, rTMS protocols, and treatment outcomes were reviewed for 196 patients with MDD who received rTMS at Saint Boniface Hospital between 2013 and 2019. Logistic regression and marginal effects were used to assess the different predictor variables for response (50% reduction or more on the Hamilton Depression Rating Scale (Ham-D)) and remission (Ham-D of ≤7 by the last session). HamD at 10 sessions was predictive of remission, and Sheehan Disability Scale (SDS) at 10 sessions was predictive of response to rTMS. Ham-D, SDS, and Beck Anxiety Inventory were predictive of remission and response by Beck Anxiety Inventory 20 sessions. High frequency rTMS had a similar response and remission rate to low frequency, but higher response rate to intermittent Theta Burst Stimulation with no difference in remission rate. Positive predictive factors of response were lower age and bupropion use. Negative predictive factors were antipsychotics, anticonvulsants, or benzodiazepine use. For remission, antipsychotics or anticonvulsants use were negative predictors; bupropion use and higher resting motor threshold were positive predictors. Severity of depression as measured by baseline HamD was not associated with different probabilities of treatment success.

Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients

Fatigue, attentional deficits and cognitive fluctuations are the most characterizing symptoms of neurological involvement in Post COVID-19 syndrome (PCS). As the intraindividual variability (IIV) in cognitive performances has been recognized as a hallmark of brain-related disorders associated with cognitive deficits, it could be an interesting measure to elucidate the mechanisms subtending both the attentive impairment and the cognitive fluctuations in these patients. By referring to IIV analysis of Reaction Times (RTs), the present study aims to define the attentive impairment and its relation to fluctuations and fatigue, in patients suffering from Post COVID-19 neurological symptoms. 74 patients were enrolled. They underwent an extensive clinical and neuropsychological assessments, as well as computerized Sustained Attention and Stroop tasks. For studying IIV, RTs distributions of performances in computerized tasks were fitted with ex-Gaussian distribution, for obtaining the τ values. Finally, the Resting Motor Threshold (RMT) was also collected to estimate cortical excitability. 29 healthy volunteers served as controls. Patients showed poorer scores in Montreal Cognitive Assessment and higher RMT, in comparison with controls. In Sustained Attention Task, Mean, µ, σ and τ values were significantly higher in PCS patients (p value = < 0.0001; 0.001; 0.018 and < 0.0001, respectively). Repeated measures ANOVA comparing the RTs mean in Stroop task within-subject and between-subjects revealed significant condition and group effect (p < 0.0001 both) and significant interaction (p = 0.005), indicating worst performances in patients. The mean of the derived interference value was significantly higher in PCS patients than in controls (p = 0.036). Patients suffering from PCS show deficits in attention, both in the sustained and executive components. Both high RTs means and high IIV subtend these deficits and could explain the often-complained cognitive fluctuations in this population.

Anesthesia inhibited corticospinal excitability and attenuated the modulation of repetitive transcranial magnetic stimulation

BackgroundLots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation.MethodsMEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation.ResultsThe RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 μV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 μV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness.ConclusionsThis study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP.

Transcranial Magnetic Stimulation in Succinic Semialdehyde Dehydrogenase Deficiency: A Measure of Maturational Trajectory of Cortical Excitability.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a disorder of GABA degradation with use-dependent downregulation of postsynaptic GABAA/B receptors. We aim to measure the resulting cortical excitation: inhibition ratio using transcranial magnetic stimulation. In this single-center observational study, 18 subjects with SSADHD and 8 healthy controls underwent transcranial magnetic stimulation. Resting motor threshold, cortical silent period, and long-interval intracortical inhibition were measured in both groups. Resting motor threshold in focal epilepsy patients from an institutional transcranial magnetic stimulation database were also included. SSADHD subjects had higher resting motor threshold than healthy controls but lower relative to focal epilepsy patients. Resting motor threshold decreased with age in all groups. Cortical silent period was longer in SSADHD subjects than in healthy controls. No difference was detected in long-interval intracortical inhibition between the 2 groups. Findings suggest abnormal corticospinal tract physiology in SSADHD, but with preserved developmental trajectory for corticospinal tract maturation. Defining features of these transcranial magnetic stimulation metrics in SSADHD will be better elucidated through this ongoing longitudinal study.

Probing the Brain-Body Connection Using Transcranial Magnetic Stimulation (TMS): Validating a Promising Tool to Provide Biomarkers of Neuroplasticity and Central Nervous System Function.

Transcranial magnetic stimulation (TMS) is a non-invasive method used to investigate neurophysiological integrity of the human neuromotor system. We describe in detail, the methodology of a single pulse TMS protocol that was performed in a large cohort of people (n = 110) with multiple sclerosis (MS). The aim was to establish and validate a core-set of TMS variables that predicted typical MS clinical outcomes: walking speed, hand dexterity, fatigue, and cognitive processing speed. We provide a brief and simple methodological pipeline to examine excitatory and inhibitory corticospinal mechanisms in MS that map to clinical status. Delayed and longer ipsilateral silent period (a measure of transcallosal inhibition; the influence of one brain hemisphere’s activity over the other), longer cortical silent period (suggestive of greater corticospinal inhibition via GABA) and higher resting motor threshold (lower corticospinal excitability) most strongly related to clinical outcomes, especially when measured in the hemisphere corresponding to the weaker hand. Greater interhemispheric asymmetry (imbalance between hemispheres) correlated with poorer performance in the greatest number of clinical outcomes. We also show, not surprisingly, that TMS variables related more strongly to motor outcomes than non-motor outcomes. As it was validated in a large sample of patients with varying severities of central nervous system dysfunction, the protocol described herein can be used by investigators and clinicians alike to investigate the role of TMS as a biomarker in MS and other central nervous system disorders.

Examination of Corticospinal and Spinal Reflexive Excitability During the Course of Postoperative Rehabilitation After Anterior Cruciate Ligament Reconstruction.

To investigate corticospinal and spinal reflexive excitability and quadriceps strength in healthy athletes and athletes after anterior cruciate ligament reconstruction (ACLR) over the course of rehabilitation. Prospective cohort study. Eighteen athletes with ACLR and 18 healthy athletes, matched by sex, age, and activity, were tested at (1) 2 weeks after surgery, (2) the "quiet knee" time point, defined as full range of motion and minimal effusion, and (3) return to running, defined as achieving a quadriceps index of 80% or greater. We measured (1) corticospinal excitability, using resting motor threshold (RMT) and motor-evoked potential amplitude at a stimulator intensity of 120% of RMT (MEP120) to the vastus medialis, (2) spinal reflexive excitability, calculating the ratio of the maximal Hoffmann reflex to the maximal M-wave to the vastus medialis, and (3) isometric quadriceps strength. The ACLR group had higher RMTs in the nonsurgical limb and higher MEP120 in the surgical limb at all time points. The healthy-athlete group did not have interlimb differences. The RMT was positively associated with quadriceps strength 2 weeks after surgery; MEP120 was associated with quadriceps strength at all time points. Compared to healthy athletes, athletes after ACLR had altered corticospinal excitability that did not change from 2 weeks after surgery to the time of return to running. J Orthop Sports Phys Ther 2020;50(9):516-522. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9329.

Surgical treatment of meningiomas located in the rolandic area: the role of navigated transcranial magnetic stimulation for preoperative planning, surgical strategy, and prediction of arachnoidal cleavage and motor outcome.

Surgical treatment of convexity meningiomas is usually considered a low-risk procedure. Nevertheless, the risk of postoperative motor deficits is higher (7.1%-24.7% of all cases) for lesions located in the rolandic region, especially when an arachnoidal cleavage plane with the motor pathway is not identifiable. The authors analyzed the possible role of navigated transcranial magnetic stimulation (nTMS) for planning resection of rolandic meningiomas and predicting the presence or lack of an intraoperative arachnoidal cleavage plane as well as the postoperative motor outcome. Clinical data were retrospectively collected from surgical cases involving patients affected by convexity, parasagittal, or falx meningiomas involving the rolandic region, who received preoperative nTMS mapping of the motor cortex (M1) and nTMS-based diffusion tensor imaging (DTI) fiber tracking of the corticospinal tract before surgery at 2 different neurosurgical centers. Surgeons' self-reported evaluation of the impact of nTMS-based mapping on surgical strategy was analyzed. Moreover, the nTMS mapping accuracy was evaluated in comparison with intraoperative neurophysiological mapping (IONM). Lastly, we assessed the role of nTMS as well as other pre- and intraoperative parameters for predicting the patients' motor outcome and the presence or absence of an intraoperative arachnoidal cleavage plane. Forty-seven patients were included in this study. The nTMS-based planning was considered useful in 89.3% of cases, and a change of the surgical strategy was observed in 42.5% of cases. The agreement of nTMS-based planning and IONM-based strategy in 35 patients was 94.2%. A new permanent motor deficit occurred in 8.5% of cases (4 of 47). A higher resting motor threshold (RMT) and the lack of an intraoperative arachnoidal cleavage plane were the only independent predictors of a poor motor outcome (p = 0.04 and p = 0.02, respectively). Moreover, a higher RMT and perilesional edema also predicted the lack of an arachnoidal cleavage plane (p = 0.01 and p = 0.03, respectively). Preoperative motor status, T2 cleft sign, contrast-enhancement pattern, and tumor volume had no predictive value. nTMS-based motor mapping is a useful tool for presurgical assessment of rolandic meningiomas, especially when a clear cleavage plane with M1 is not present. Moreover, the RMT can indicate the presence or absence of an intraoperative cleavage plane and predict the motor outcome, thereby helping to identify high-risk patients before surgery.

Primary lateral sclerosis and the amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum of diseases. Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n = 27) and ALS-FTD (n = 12). Clinical features, Addenbrooke's Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS). Global cognition was impaired in PLS (mean total ACE score 82.5 ± 13.6), similar to ALS-FTD (mean total ACE score 76.3 ± 7.7, p > 0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5 ± 6.2) compared ALS-FTD (50.1 ± 7.2, p < 0.001) and ALS (62.3 ± 12.6, p = 0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4 ± 22.4months) and shortest in ALS-FTD (38.5 ± 4.5months, p = 0.002). Bulbar onset disease (β = - 0.45, p = 0.007) and RMT (β = 0.54, p = 0.001) were independent predictors of global cognition while motor scores (β = 0.47, p = 0.036) and SICI (β = 0.58, p = 0.006) were significantly associated with ALSFRS. The cognitive profile in PLS resembles ALS-FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS-FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS-FTD. Overall, while these findings support the notion that PLS lies on the ALS-FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

The role of pulse shape in motor cortex transcranial magnetic stimulation using full-sine stimuli.

A full-sine (biphasic) pulse waveform is most commonly used for repetitive transcranial magnetic stimulation (TMS), but little is known about how variations in duration or amplitude of distinct pulse segments influence the effectiveness of a single TMS pulse to elicit a corticomotor response. Using a novel TMS device, we systematically varied the configuration of full-sine pulses to assess the impact of configuration changes on resting motor threshold (RMT) as measure of stimulation effectiveness with single-pulse TMS of the non-dominant motor hand area (M1). In young healthy volunteers, we (i) compared monophasic, half-sine, and full-sine pulses, (ii) applied two-segment pulses consisting of two identical half-sines, and (iii) manipulated amplitude, duration, and current direction of the first or second full-sine pulse half-segments. RMT was significantly higher using half-sine or monophasic pulses compared with full-sine. Pulses combining two half-sines of identical polarity and duration were also characterized by higher RMT than full-sine stimuli resulting. For full-sine stimuli, decreasing the amplitude of the half-segment inducing posterior-anterior oriented current in M1 resulted in considerably higher RMT, whereas varying the amplitude of the half-segment inducing anterior-posterior current had a smaller effect. These findings provide direct experimental evidence that the pulse segment inducing a posterior-anterior directed current in M1 contributes most to corticospinal pathway excitation. Preferential excitation of neuronal target cells in the posterior-anterior segment or targeting of different neuronal structures by the two half-segments can explain this result. Thus, our findings help understanding the mechanisms of neural stimulation by full-sine TMS.

Abnormal Corticospinal Excitability in Patients with Disorders of Consciousness

BackgroundTranscranial magnetic stimulation (TMS) has been frequently used to explore changes in the human motor cortex in different conditions, while the extent of motor cortex reorganization in patients in vegetative state (VS) (now known as unresponsive wakefulness syndrome, UWS) and minimally conscious (MCS) states due to severe brain damage remains largely unknown. Objective/hypothesisIt was hypothesized that cortical motor excitability would be decreased and would correlate to the level of consciousness in patients with disorders of consciousness. MethodsCorticospinal excitability was assessed in 47 patients (24 VS/UWS and 23 MCS) and 14 healthy controls. The test parameters included maximal peak-to-peak M-wave (Mmax), F-wave persistence, peripheral and central motor conduction times, sensory (SEP) and motor evoked (MEP) potential latencies and amplitudes, resting motor threshold (RMT), stimulus/response curves, and short latency afferent inhibition (SAI). TMS measurements were correlated to the level of consciousness (assessed using the Coma Recovery Scale-Revised). ResultsOn average, the patient group had lower Mmax, lower MEP and SEP amplitudes, higher RMTs, narrower stimulus/response curves, and reduced SAI compared to the healthy controls (P < 0.05). The SAI alterations were correlated to the level of consciousness (P < 0.05). ConclusionsThe findings demonstrated the impairment of the cortical inhibitory circuits in patients with disorders of consciousness. Moreover, the significant relationship was found between cortical inhibition and clinical consciousness dysfunction.

Chronic Ankle Instability and Corticomotor Excitability of the Fibularis Longus Muscle

Neuromuscular deficits are common in people with chronic ankle instability (CAI). Corticomotor pathways are very influential in the production of voluntary muscle function, yet these pathways have not been evaluated in people with CAI. To determine if corticomotor excitability of the fibularis longus (FL) differs between individuals with unilateral CAI and matched control participants without CAI. Case-control study. Laboratory. Patients or Other Participants: Ten people with CAI (4 men, 6 women; age = 21.2 ± 1.23 years, height = 175.13 ± 9.7 cm, mass = 77.1 ± 13.58 kg) and 10 people without CAI (4 men, ± women; age = 21.2 ± 2.3 years; height = 172.34 ± 8.86 cm, mass = 73.4 ± 7.15 kg) volunteered for this study. Transcranial magnetic stimulation was performed over the motor cortex on neurons corresponding with the FL. All testing was performed with the participant in a seated position with a slightly flexed knee joint and the ankle secured in 10 8 of plantar flexion. The resting motor threshold (RMT), which was expressed as a percentage of 2 T, was considered the lowest amount of magnetic energy that would induce an FL motor evoked potential equal to or greater than 20 l V, as measured with surface electromyography, on 7 consecutive stimuli. In addition, the Functional Ankle Disability Index (FADI) and FADI Sport were used to assess self-reported function. Higher RMTs were found in the injured and uninjured FL of the CAI group (60.8% ± 8.4% and 59.1% ± 8.99%, respectively) than the healthy group (52.8% ± 8.56% and 52% ± 7.0%, respectively; F(1,18) = 4.92, P = .04). No leg x group interactions (F(1,18) = 0.1, P = .76) or between-legs differences (F(1,18) = 0.74, P = .40) were found. A moderate negative correlation was found between RMT and FADI (r = 0.4, P = .04) and FADI Sport (r = 0.44, P = .03), suggesting that higher RMT is related to lower self-reported function. Higher bilateral RMTs may indicate deficits in FL corticomotor excitability in people with CAI. In addition, a moderate correlation between RMT and FADI suggests that cortical excitability deficits may be influential in altering function.

The Effects of 30Hz Theta Burst Transcranial Magnetic Stimulation (P01.171)

Objective: To examine the effects of 30Hz Theta Burst Transcranial Magnetic Stimulation (TBS) in healthy adults. Background The safety parameters of the Magstim SuperRapid2® limit the stimulation intensity of 50Hz TBS. By lowering the burst frequency to 30Hz, we are able to increase this limit, thus expanding the population that may participate in TBS research. Design/Methods: Seventeen right-handed healthy adults (32.5+/-9.3years; M:F=7:10) completed intermittent and continuous TBS (iTBS, cTBS) over the left motor cortex. TBS was performed with Magstim SuperRapid2® using published settings, except: 1) stimulation intensity was set higher, at 90% of Resting Motor Threshold (RMT), and 2) 30Hz, rather than 50Hz, burst frequency was used. Motor-Evoked Potentials (MEP) in the right first dorsal interosseous muscle were measured before, and one and 10 minutes after TBS. Before and 20 minutes after TBS, subjects also completed a stop-signal choice reaction time task consisting of choosing either X or O after a visual cue but stopping when a tone follows. The delay time for the tone is automatically adjusted to yield a ∼50% accuracy in the stop signal inhibition. Stop Signal Reaction Time (SSRT) is calculated by subtracting the Mean tone Delay (MD) from the Choice Reaction Time (CRT). We used repeated-measures ANOVA to compare MEPs and paired t-test to analyze stop-signal task measures. Results: 30Hz iTBS increased, while cTBS decreased MEP amplitudes with a significant Group*Time effect (p=0.009). After iTBS, CRT (p=0.006) and MD (p=0.010) increased. SSRT was not different (p=0.40). Reaction time measures did not change after cTBS. Conclusions: Similar to conventional (50Hz) TBS, 30Hz iTBS increases and cTBS decreases MEP amplitudes. Uniquely, 30Hz iTBS significantly changed responses on several stop signal reaction time measures. This technique, which can be used with higher intensities, merits further exploration in populations such as children who have higher RMTs. Supported by: 1. Tourette Syndrome Association (Steve Wu) 2. R01 MH081854 (Donald Gilbert). Disclosure: Dr. Gilbert has received personal compensation in an editorial capacity for Pediatrics Review and Education Program R11. Dr. Gilbert has received research support from Psyadon Pharmaceuticals and Otsuka Pharmaceuticals. Dr. Shahana has nothing to disclose. Dr. Huddleston has nothing to disclose. Dr. Wu has received research support from Psyadon Pharmaceuticals, Otsuka Pharmaceutical and Genzyme Corporation.

Paradoxical Alteration in Cortical Excitability Following 10 Hz rTMS in Patients with Untreated Obstructive Sleep Apnea Syndrome (OSAS) (P05.007)

Objective: To investigate changes in cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) undergoing 10Hz repetitive transcranial magnetic stimulation (rTMS) during wakefulness. Background OSAS is a syndrome characterized by repetitive upper airway collapse or narrowing during sleep with sequelae include adverse cardiovascular and metabolic outcomes, decline in quality of life, and neurocognitive impairment. Although altered cortical excitability in OSAS is well documented, the effect of rTMS on the excitability changes in OSAS patients has not previously been studied. This is important as rTMS can potentially be used as an adjunct therapy in OSAS. Design/Methods: We recruited 13 untreated severe OSAS (10 males, mean apnea-hypopnea index=54.6±13.01h) patients and 12 age-matched healthy volunteers. The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, central motor conduction time (CMCT), cortical silent period (CSP) and short-interval intracortical inhibition (SICI). These parameters were measured in the morning more than 2h after arising. After the baseline TMS studies, the patients and healthy volunteers were subjected to 10 Hz rTMS over left dorsolateral prefrontal cortex. The TMS parameters (RMT, MEP, CMCT, CSP and SICI) were repeated thereafter. Results: OSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p 0.05). The rTMS showed an prolongation of CSP in OSAS subjects (ANOVA, p Conclusions: This TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day. The paradoxical response of rTMS in OSAS patients highlights the complex interplay of excitatory and inhibitory cortical circuits in OSAS. This intriguing result needs further replication. Disclosure: Dr. Das has nothing to disclose. Dr. Vijayakumari has nothing to disclose. Dr. Radhakrishnan has nothing to disclose.