Local Dynamic Stability of Trunk During Gait is Responsive to Rehabilitation in Subjects with Primary Degenerative Cerebellar Ataxia.

This study aimed to assess the responsiveness to the rehabilitation of three trunk acceleration-derived gait indexes, namely the harmonic ratio (HR), the short-term longest Lyapunov's exponent (sLLE), and the step-to-step coefficient of variation (CV), in a sample of subjects with primary degenerative cerebellar ataxia (swCA), and investigate the correlations between their improvements (∆), clinical characteristics, and spatio-temporal and kinematic gait features. The trunk acceleration patterns in the antero-posterior (AP), medio-lateral (ML), and vertical (V) directions during gait of 21 swCA were recorded using a magneto-inertial measurement unit placed at the lower back before (T0) and after (T1) a period of inpatient rehabilitation. For comparison, a sample of 21 age- and gait speed-matched healthy subjects (HSmatched) was also included. At T1, sLLE in the AP (sLLEAP) and ML (sLLEML) directions significantly improved with moderate to large effect sizes, as well as SARA scores, stride length, and pelvic rotation. sLLEML and pelvic rotation also approached the HSmatched values at T1, suggesting a normalization of the parameter. HRs and CV did not significantly modify after rehabilitation. ∆sLLEML correlated with ∆ of the gait subscore of the SARA scale (SARAGAIT) and ∆stride length and ∆sLLEAP correlated with ∆pelvic rotation and ∆SARAGAIT. The minimal clinically important differences for sLLEML and sLLEAP were ≥ 36.16% and ≥ 28.19%, respectively, as the minimal score reflects a clinical improvement in SARA scores. When using inertial measurement units, sLLEAP and sLLEML can be considered responsive outcome measures for assessing the effectiveness of rehabilitation on trunk stability during walking in swCA.

Optimizing Rare Disease Gait Classification through Data Balancing and Generative AI: Insights from Hereditary Cerebellar Ataxia.

The interpretability of gait analysis studies in people with rare diseases, such as those with primary hereditary cerebellar ataxia (pwCA), is frequently limited by the small sample sizes and unbalanced datasets. The purpose of this study was to assess the effectiveness of data balancing and generative artificial intelligence (AI) algorithms in generating synthetic data reflecting the actual gait abnormalities of pwCA. Gait data of 30 pwCA (age: 51.6 ± 12.2 years; 13 females, 17 males) and 100 healthy subjects (age: 57.1 ± 10.4; 60 females, 40 males) were collected at the lumbar level with an inertial measurement unit. Subsampling, oversampling, synthetic minority oversampling, generative adversarial networks, and conditional tabular generative adversarial networks (ctGAN) were applied to generate datasets to be input to a random forest classifier. Consistency and explainability metrics were also calculated to assess the coherence of the generated dataset with known gait abnormalities of pwCA. ctGAN significantly improved the classification performance compared with the original dataset and traditional data augmentation methods. ctGAN are effective methods for balancing tabular datasets from populations with rare diseases, owing to their ability to improve diagnostic models with consistent explainability.

Identification of Gait Unbalance and Fallers Among Subjects with Cerebellar Ataxia by a Set of Trunk Acceleration-Derived Indices of Gait.

This study aimed to assess the ability of 25 gait indices to characterize gait instability and recurrent fallers among persons with primary degenerative cerebellar ataxia (pwCA), regardless of gait speed, and investigate their correlation with clinical and kinematic variables. Trunk acceleration patterns were acquired during the gait of 34 pwCA, and 34 age- and speed-matched healthy subjects (HSmatched) using an inertial measurement unit. We calculated harmonic ratios (HR), percent recurrence, percent determinism, step length coefficient of variation, short-time largest Lyapunov exponent (sLLE), normalized jerk score, log-dimensionless jerk (LDLJ-A), root mean square (RMS), and root mean square ratio of accelerations (RMSR) in each spatial direction for each participant. Unpaired t-tests or Mann-Whitney tests were performed to identify significant differences between the pwCA and HSmatched groups. Receiver operating characteristics were plotted to assess the ability to characterize gait alterations in pwCA and fallers. Optimal cutoff points were identified, and post-test probabilities were calculated. The HRs showed to characterize gait instability and pwCA fallers with high probabilities. They were correlated with disease severity and stance, swing, and double support duration, regardless of gait speed. sLLEs, RMSs, RMSRs, and LDLJ-A were slightly able to characterize the gait of pwCA but failed to characterize fallers.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Central sensitization mechanisms in chronic migraine with medication overuse headache: a study of thalamocortical activation and lateral cortical inhibition.

BACKGROUND: It is unclear whether cortical hyperexcitability in chronic migraine with medication overuse headache (CM-MOH) is due to increased thalamocortical drive or aberrant cortical inhibitory mechanisms. METHODS: Somatosensory evoked potentials (SSEP) were performed by electrical stimulation of the median nerve (M), ulnar nerve (U) and simultaneous stimulation of both nerves (MU) in 27 patients with CM-MOH and, for comparison, in 23 healthy volunteers (HVs) of a comparable age distribution. We calculated the degree of cortical lateral inhibition using the formula: 100 - [MU/(M + U) × 100] and the level of thalamocortical activation by analyzing the high frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. RESULTS: Compared to HV, CM-MOH patients showed higher lateral inhibition (CM-MOH 52.2% ± 15.4 vs. HV 40.4% ± 13.3; p = 0.005), which positively correlated with monthly headache days, and greater amplitude of pre-synaptic HFOs (p = 0.010) but normal post-synaptic HFOs (p = 0.122). CONCLUSION: Our findings suggest that central neuronal circuits are highly sensitized in CM-MOH patients, at both thalamocortical and cortical levels. The observed changes could be due to the combination of dysfunctional central pain control mechanisms, hypersensitivity and hyperresponsiveness directly linked to the chronic intake of acute migraine drugs.

Characterization of prosthetic knees through a low-dimensional description of gait kinematics.

The characterization of both limbs' behaviour in prosthetic gait is of key importance for improving the prosthetic components and increasing the biomechanical capability of trans-femoral amputees. When characterizing human gait, modular motor control theories have been proven to be powerful in providing a compact description of the gait patterns. In this paper, the planar covariation law of lower limb elevation angles is proposed as a compact, modular description of prosthetic gait; this model is exploited for a comparison between trans-femoral amputees walking with different prosthetic knees and control subjects walking at different speeds. Results show how the planar covariation law is maintained in prostheses users, with a similar spatial organization and few temporal differences. Most of the differences among the different prosthetic knees are found in the kinematic coordination patterns of the sound side. Moreover, different geometrical parameters have been calculated over the common projected plane, and their correlation with classical gait spatiotemporal and stability parameters has been investigated. The results from this latter analysis have highlighted a correlation with several parameters of gait, suggesting that this compact description of kinematics unravels a significant biomechanical meaning. These results can be exploited to guide the control mechanisms of prosthetic devices based purely on the measurement of relevant kinematic quantities.

A Proof of Concept Combined Using Mixed Reality for Personalized Neurorehabilitation of Cerebellar Ataxic Patients.

BACKGROUND: Guidelines for degenerative cerebellar ataxia neurorehabilitation suggest intensive coordinative training based on physiotherapeutic exercises. Scientific studies demonstrate virtual exergaming therapeutic value. However, patient-based personalization, post processing analyses and specific audio-visual feedbacks are not provided. This paper presents a wearable motion tracking system with recording and playback features. This system has been specifically designed for ataxic patients, for upper limbs coordination studies with the aim to retrain movement in a neurorehabilitation setting. Suggestions from neurologists and ataxia patients were considered to overcome the shortcomings of virtual systems and implement exergaming. METHODS: The system consists of the mixed-reality headset Hololens2 and a proprietary exergaming implemented in Unity. Hololens2 can track and save upper limb parameters, head position and gaze direction in runtime. RESULTS: Data collected from a healthy subject are reported to demonstrate features and outputs of the system. CONCLUSIONS: Although further improvements and validations are needed, the system meets the needs of a dynamic patient-based exergaming for patients with cerebellar ataxia. Compared with existing solutions, the mixed-reality system is designed to provide an effective and safe therapeutic exergaming that supports both primary and secondary goals of an exergaming: what a patient should do and how patient actions should be performed.

Multiscale Entropy Algorithms to Analyze Complexity and Variability of Trunk Accelerations Time Series in Subjects with Parkinson's Disease.

The aim of this study was to assess the ability of multiscale sample entropy (MSE), refined composite multiscale entropy (RCMSE), and complexity index (CI) to characterize gait complexity through trunk acceleration patterns in subjects with Parkinson's disease (swPD) and healthy subjects, regardless of age or gait speed. The trunk acceleration patterns of 51 swPD and 50 healthy subjects (HS) were acquired using a lumbar-mounted magneto-inertial measurement unit during their walking. MSE, RCMSE, and CI were calculated on 2000 data points, using scale factors (τ) 1-6. Differences between swPD and HS were calculated at each τ, and the area under the receiver operating characteristics, optimal cutoff points, post-test probabilities, and diagnostic odds ratios were calculated. MSE, RCMSE, and CIs showed to differentiate swPD from HS. MSE in the anteroposterior direction at τ4 and τ5, and MSE in the ML direction at τ4 showed to characterize the gait disorders of swPD with the best trade-off between positive and negative posttest probabilities and correlated with the motor disability, pelvic kinematics, and stance phase. Using a time series of 2000 data points, a scale factor of 4 or 5 in the MSE procedure can yield the best trade-off in terms of post-test probabilities when compared to other scale factors for detecting gait variability and complexity in swPD.

The monoclonal CGRP-receptor blocking antibody erenumab has different effects on brainstem and cortical sensory-evoked responses.

OBJECTIVES: It is unclear whether the electrophysiological effects of erenumab, a monoclonal antibody against the calcitonin gene-related peptide receptor, occur only at the periphery of the trigeminal system or centrally and at the cortical level. METHODS: We prospectively enrolled 20 patients with migraine who had failed at least two preventative treatments. We measured the nociceptive blink reflex and non-noxious somatosensory evoked potentials in all participants. The area under the curve and habituation of the second polysynaptic nociceptive blink reflex component (R2) as well as the amplitude and habituation of somatosensory evoked potentials N20-P25 were measured. Electrophysiological data were collected at baseline (T0), 28 days (T1), and 56 days (T2) before each injection of erenumab (70 mg). RESULTS: Erenumab reduced the patients' mean monthly headache days, headache intensity, and acute medication intake considerably at T1 and T2 (all p < 0.05). The nociceptive blink reflex area under the curve was considerably lower at T1 and T2 than at baseline without changing the habituation slope. At T2, there was a significant increase in the delayed somatosensory evoked potentials amplitude reduction (habituation) but not in the initial cortical activation. CONCLUSION: Our findings showed that erenumab, in addition to its well-known peripheral effects, can induce central effects earlier in the brainstem and later in the cortex. We cannot rule out whether these results are due to a direct effect of erenumab on the central nervous system or an indirect effect secondary to peripheral drug modulation.

Bimodal sensory integration in migraine: A study of the effect of visual stimulation on somatosensory evoked cortical responses.

BACKGROUND: Merging of sensory information is a crucial process for adapting the behaviour to the environment in all species. It is not known if this multisensory integration might be dysfunctioning interictally in migraine without aura, where sensory stimuli of various modalities are processed abnormally when delivered separately. To investigate this question, we compared the effects of a concomitant visual stimulation on conventional low-frequency somatosensory evoked potentials and embedded high-frequency oscillations between migraine patients and healthy volunteers. METHODS: We recorded somatosensory evoked potentials in 19 healthy volunteers and in 19 interictal migraine without aura patients before, during, and 5 min after (T2) simultaneous synchronous pattern-reversal visual stimulation. At each time point, we measured amplitude and habituation of the N20-P25 low-frequency-somatosensory evoked potentials component and maximal peak-to-peak amplitude of early and late bursts of high-frequency oscillations. RESULTS: In healthy volunteers, the bimodal stimulation significantly reduced low-frequency-somatosensory evoked potentials habituation and tended to reduce early high-frequency oscillations that reflect thalamocortical activity. By contrast, in migraine without aura patients, bimodal stimulation significantly increased low-frequency-somatosensory evoked potentials habituation and early high-frequency oscillations. At T2, all visual stimulation-induced changes of somatosensory processing had vanished. CONCLUSION: These results suggest a malfunctioning multisensory integration process, which could be favoured by an abnormal excitability level of thalamo-cortical loops.

Reversible conduction block of peroneal nerve associated with SARS-CoV-2.

BACKGROUND: The ongoing SARS-CoV-2 pandemic, which is dramatically spreading worldwide, is well known for its respiratory sequelae. Besides cases of Guillain-Barré Syndrome, encephalitis, hyposmia, the whole range of neurological complications due to SARSCoV-2 is still not well known. METHODS AND FINDINGS: Herein, we report a new case of COVID-19, associated with mononeuropathy with reversible conduction block (CB). After SARS-CoV-2 infection, the patient developed acute weakness of left peroneal muscles. He underwent an endovenous immunoglobulin treatment, and symptoms improved. Two electroneurographic exam (before and after treatment), showed a reversible CB on left peroneal nerve. Dosage of serum antiganglioside antibodies showed anti-GM1 IgM positivity. CONCLUSIONS: The present case gives new informations about reversible CB neuropathy as an acute presentation of SARS-CoV-2. Besides, antiganglioside antibodies evaluation could be useful to understand etiology of the increasing number of neurological manifestations related to SARS-CoV-2.

Neuromodulation for Chronic Daily Headache.

PURPOSE OF REVIEW: We reviewed the literature that explored the use of central and peripheral neuromodulation techniques for chronic daily headache (CDH) treatment. RECENT FINDINGS: Although the more invasive deep brain stimulation (DBS) is effective in chronic cluster headache (CCH), it should be reserved for extremely difficult-to-treat patients. Percutaneous occipital nerve stimulation has shown similar efficacy to DBS and is less risky in both CCH and chronic migraine (CM). Non-invasive transcutaneous vagus nerve stimulation is a promising add-on treatment for CCH but not for CM. Transcutaneous external trigeminal nerve stimulation may be effective in treating CM; however, it has not yet been tested for cluster headache. Transcranial magnetic and electric stimulations have promising preventive effects against CM and CCH. Although the precise mode of action of non-invasive neuromodulation techniques remains largely unknown and there is a paucity of controlled trials, they should be preferred to more invasive techniques for treating CDH.

Machine Learning Approach to Support the Detection of Parkinson's Disease in IMU-Based Gait Analysis.

The aim of this study was to determine which supervised machine learning (ML) algorithm can most accurately classify people with Parkinson's disease (pwPD) from speed-matched healthy subjects (HS) based on a selected minimum set of IMU-derived gait features. Twenty-two gait features were extrapolated from the trunk acceleration patterns of 81 pwPD and 80 HS, including spatiotemporal, pelvic kinematics, and acceleration-derived gait stability indexes. After a three-level feature selection procedure, seven gait features were considered for implementing five ML algorithms: support vector machine (SVM), artificial neural network, decision trees (DT), random forest (RF), and K-nearest neighbors. Accuracy, precision, recall, and F1 score were calculated. SVM, DT, and RF showed the best classification performances, with prediction accuracy higher than 80% on the test set. The conceptual model of approaching ML that we proposed could reduce the risk of overrepresenting multicollinear gait features in the model, reducing the risk of overfitting in the test performances while fostering the explainability of the results.

Ability of a Set of Trunk Inertial Indexes of Gait to Identify Gait Instability and Recurrent Fallers in Parkinson's Disease.

The aims of this study were to assess the ability of 16 gait indices to identify gait instability and recurrent fallers in persons with Parkinson's disease (pwPD), regardless of age and gait speed, and to investigate their correlation with clinical and kinematic variables. The trunk acceleration patterns were acquired during the gait of 55 pwPD and 55 age-and-speed matched healthy subjects using an inertial measurement unit. We calculated the harmonic ratios (HR), percent recurrence, and percent determinism (RQAdet), coefficient of variation, normalized jerk score, and the largest Lyapunov exponent for each participant. A value of ≤1.50 for the HR in the antero-posterior direction discriminated between pwPD at Hoehn and Yahr (HY) stage 3 and healthy subjects with a 67% probability, between pwPD at HY 3 and pwPD at lower HY stages with a 73% probability, and it characterized recurrent fallers with a 77% probability. Additionally, HR in the antero-posterior direction was correlated with pelvic obliquity and rotation. RQAdet in the antero-posterior direction discriminated between pwPD and healthy subjects with 67% probability, regardless of the HY stage, and was correlated with stride duration and cadence. Therefore, HR and RQAdet in the antero-posterior direction can both be used as age- and-speed-independent markers of gait instability.

Thalamo-cortical networks in subtypes of migraine with aura patients.

BACKGROUND: We searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom. METHODS: 3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores. RESULTS: As compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs. CONCLUSIONS: The present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.

Impairment of Global Lower Limb Muscle Coactivation During Walking in Cerebellar Ataxias.

The aim of this study was to investigate the time-varying multi-muscle coactivation function (TMCf) in the lower limbs during gait and its relationship with the biomechanical and clinical features of patients with cerebellar ataxia. A total of 23 patients with degenerative cerebellar ataxia (16 with spinocerebellar ataxia, 7 with adult-onset ataxia of unknown etiology) and 23 age-, sex-, and speed-matched controls were investigated. The disease severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) in all patients. During walking, simultaneous acquisition of kinematic, kinetic, and electromyography data was performed using a motion analysis system. The coactivation was processed throughout the gait cycle using the TMCf, and the following parameters were measured: synthetic coactivation index, full width at half maximum, and center of activity. Spatiotemporal (walking speed, stance duration, swing duration, first and second double-support durations, step length, step width, stride length, Center of Mass displacement), kinetic (vertical component of GRFs), and energy consumption (total energy consumption and mechanical energy recovered) parameters were also measured. The coactivation variables were compared between patients and controls and were correlated with both clinical and gait variables. A significantly increased global TMCf was found in patients compared with controls. In addition, the patients showed a significant shift of the center of activity toward the initial contact and a significant reduction in energy recovery. All coactivation parameters were negatively correlated with gait speed, whereas the coactivation index and center of activity were positively correlated with both center-of-mass mediolateral displacement values and SARA scores. Our findings suggest that patients use global coactivation as a compensatory mechanism during the earliest and most challenging subphase (loading response) of the gait cycle to reduce the lateral body sway, thus improving gait stability at the expense of effective energy recovery. This information could be helpful in optimizing rehabilitative treatment aimed at improving lower limb muscle control during gait in patients with cerebella ataxia.

Global Muscle Coactivation of the Sound Limb in Gait of People with Transfemoral and Transtibial Amputation.

The aim of this study was to analyze the effect of the level of amputation and various prosthetic devices on the muscle activation of the sound limb in people with unilateral transfemoral and transtibial amputation. We calculated the global coactivation of 12 muscles using the time-varying multimuscle coactivation function method in 37 subjects with unilateral transfemoral amputation (10, 16, and 11 with mechanical, electronic, and bionic prostheses, respectively), 11 subjects with transtibial amputation, and 22 healthy subjects representing the control group. The results highlighted that people with amputation had a global coactivation temporal profile similar to that of healthy subjects. However, amputation increased the level of the simultaneous activation of many muscles during the loading response and push-off phases of the gait cycle and decreased it in the midstance and swing subphases. This increased coactivation probably plays a role in prosthetic gait asymmetry and energy consumption. Furthermore, people with amputation and wearing electronic prosthesis showed lower global coactivation when compared with people wearing mechanical and bionic prostheses. These findings suggest that the global lower limb coactivation behavior can be a useful tool to analyze the motor control strategies adopted and the ability to adapt to the prosthetic device.

Patients with chronic migraine without history of medication overuse are characterized by a peculiar white matter fiber bundle profile.

BACKGROUND: We investigated intracerebral fiber bundles using a tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to verify microstructural integrity in patients with episodic (MO) and chronic migraine (CM). METHODS: We performed DTI in 19 patients with MO within interictal periods, 18 patients with CM without any history of drug abuse, and 18 healthy controls (HCs) using a 3 T magnetic resonance imaging scanner. We calculated diffusion metrics, including fractional anisotropy (FA), axial diffusion (AD), radial diffusion (RD), and mean diffusion (MD). RESULTS: TBSS revealed no significant differences in the FA, MD, RD, and AD maps between the MO and HC groups. In comparison to the HC group, the CM group exhibited widespread increased RD (bilateral superior [SCR] and posterior corona radiata [PCR], bilateral genu of the corpus callosum [CC], bilateral posterior limb of internal capsule [IC], bilateral superior longitudinal fasciculus [LF]) and MD values (tracts of the right SCR and PCR, right superior LF, and right splenium of the CC). In comparison to the MO group, the CM group showed decreased FA (bilateral SCR and PCR, bilateral body of CC, right superior LF, right forceps minor) and increased MD values (bilateral SCR and right PCR, right body of CC, right superior LF, right splenium of CC, and right posterior limb of IC). CONCLUSION: Our results suggest that chronic migraine can be associated with the widespread disruption of normal white matter integrity in the brain.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BACKGROUND: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. METHODS: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation. RESULTS: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI. CONCLUSIONS: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.