Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients

Background: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. Methods: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). Results: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. Conclusions: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

Ipsilateral Motor Pathways and Transcallosal Inhibition During Lower Limb Movement After Stroke

Background Stroke rehabilitation may be improved with a better understanding of the contribution of ipsilateral motor pathways to the paretic limb and alterations in transcallosal inhibition. Few studies have evaluated these factors during dynamic, bilateral lower limb movements, and it is unclear whether they relate to functional outcomes. Objective Determine if lower limb ipsilateral excitability and transcallosal inhibition after stroke depend on target limb, task, or number of limbs involved, and whether these factors are related to clinical measures. Methods In 29 individuals with stroke, ipsilateral and contralateral responses to transcranial magnetic stimulation were measured in the paretic and nonparetic tibialis anterior during dynamic (unilateral or bilateral ankle dorsiflexion/plantarflexion) and isometric (unilateral dorsiflexion) conditions. Relative ipsilateral excitability and transcallosal inhibition were assessed. Fugl-Meyer, ankle movement accuracy, and walking characteristics were assessed. Results Relative ipsilateral excitability was greater during dynamic than isometric conditions in the paretic limb ( P ≤ .02) and greater in the paretic than the nonparetic limb during dynamic conditions ( P ≤ .004). Transcallosal inhibition was greater in the ipsilesional than contralesional hemisphere ( P = .002) and during dynamic than isometric conditions ( P = .03). Greater ipsilesional transcallosal inhibition was correlated with better ankle movement accuracy ( R2 = 0.18, P = .04). Greater contralateral excitability to the nonparetic limb was correlated with improved walking symmetry ( R2 = 0.19, P = .03). Conclusions Ipsilateral pathways have increased excitability to the paretic limb, particularly during dynamic tasks. Transcallosal inhibition is greater in the ipsilesional than contralesional hemisphere and during dynamic than isometric tasks. Ipsilateral pathways and transcallosal inhibition may influence walking asymmetry and ankle movement accuracy.

Combining transcranial direct current stimulation with aerobic exercise to optimize cortical priming in stroke

Aerobic exercise (AE) and transcranial direct current stimulation (tDCS) are priming techniques that have been studied for their potential neuromodulatory effects on corticomotor excitability (CME), however the synergistic effects of AE and tDCS are not explored in stroke. Here we investigated the synergistic effects of AE and tDCS on CME, intracortical and transcallosal inhibition, and motor control for the lower limb in stroke. 26 stroke survivors participated in three sessions - tDCS, AE and AE + tDCS. AE included moderate intensity exercise and tDCS included 1 mA of anodal tDCS to the lower limb motor cortex with or without AE. Outcomes included measures of CME, short interval intracortical inhibition (SICI), ipsilateral silent period (iSP) (an index of transcallosal inhibition) for the tibialis anterior and ankle reaction time. Ipsilesional CME significantly decreased for AE compared to AE + tDCS and tDCS. No differences were noted in SICI, iSP measures or reaction time between all three sessions. Our findings suggest that a combination of exercise and tDCS, and tDCS demonstrate greater excitability of the ipsilesional hemisphere compared to exercise only, however these effects were specific to the descending corticomotor pathways. No additive priming effects of exercise and tDCS over tDCS was observed. Novelty: • An exercise and tDCS paradigm upregulated the descending motor pathways from the ipsilesional lower limb M1 compared to exercise. • Exercise or tDCS administered alone or in combination did not affect intracortical or transcallosal inhibition or reaction time.

018 Role of transcallosal inhibition in disease spread in ALS

IntroductionThere is substantial evidence for the cortical origin of amyotrophic lateral sclerosis (ALS). Impaired function of the corpus callosum has been demonstrated in ALS patients and may play a role in disease spread, potentially mediating the spread of cortical hyperexcitability between hemispheres. We assessed transcallosal inhibition, utilising the threshold tracking transcranial magnetic stimulation (TMS) technique to assess transcallosal inhibition and related the changes to disease involvement.MethodsThreshold tracking TMS was undertaken in 15 ALS patients and results were compared to 16 healthy controls. Interhemispheric inhibition was assessed using a figure of eight coil over each hemisphere across interstimulus intervals ranging from 8 to 40ms.ResultsTranscallosal inhibition was reduced in ALS patients (0.9 ± 1.0%) when compared to controls (6.6 ± 1.0%, P=0.03). Importantly differences in transcallosal inhibition between hemispheres were evident in ALS patients. Specifically, transcallosal inhibition projecting from the motor cortex contralateral to disease onset (0.9 ± 1.0%) was significantly lower when compared to projection form the ipsilateral motor cortex (3.2 ± 1.0%, P=0.036). Abnormalities of transcallosal inhibition correlated with upper motor neurone dysfunction and greater functional disability in ALS.ConclusionAbnormalities of transcallosal inhibition were demonstrated in ALS patients and were associated with clinical features. Consequently, dysfunction of transcallosal fibres may contribute to development of cortical hyperexcitability, a pathogenic mechanism in ALS. Strategies aimed at modulating dysfunction may prove therapeutically useful in ALS.