Long-lasting TMS motor threshold elevation in mild traumatic brain injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is very common, and part of the patients experience persistent symptoms. These may be caused by diffuse neuronal damage and could therefore affect cortical excitability. The motor threshold (MT), measured by transcranial magnetic stimulation (TMS), is a measure of cortical excitability and cortico-spinal tract integrity. MATERIALS AND METHODS: We used navigated TMS (nTMS) and electromyography to determine subjects' left hemisphere MTs. Nineteen subjects with mTBI (11 with persistent symptoms and eight fully recovered) and nine healthy controls were tested. The injuries had occurred on average 5 years earlier. All participants had normal brain MRIs, that is, no signs of injury. None used centrally acting medication. RESULTS: The mean MT in controls was 43.0% (SD 2.5) of maximum stimulator output. The mTBI subjects mean MT was 53.4% (SD 9.7), being higher than the controls' threshold. Subjective recovery did not correlate with MT. CONCLUSIONS: The results show chronic MT elevation in a sample of subjects with symptomatic or recovered mTBI. This suggests that mTBI may be compensated, although not fully recovered, years after the injury. While the cause for MT elevation cannot be concluded from these preliminary observations, possible explanations include decreased cortical excitability and impaired subcortical conduction.

Combined use of non-invasive techniques for improved functional localization for a selected group of epilepsy surgery candidates.

Invasive cortical mapping is conventionally required for preoperative identification of epileptogenic and eloquent cortical regions before epilepsy surgery. The decision on the extent and exact location of the resection is always demanding and multimodal approach is desired for added certainty. The present study describes two non-invasive preoperative protocols, used in addition to the normal preoperative work-up for localization of the epileptogenic and sensorimotor cortical regions, in two young patients with epilepsy. Magnetoencephalography (MEG) was used to determine the primary somatosensory cortex (S1) and the ictal onset zones. Navigated transcranial magnetic stimulation (nTMS) was used to determine the location and the extent of the primary motor representation areas. The localization results from these non-invasive methods were used for guiding the subdural grid deployment and later compared with the results from electrical cortical stimulation (ECS) via subdural grids, and validated by surgery outcome. The results from MEG and nTMS localizations were consistent with the ECS results and provided improved spatial precision. Consistent results of our study suggest that these non-invasive methods can be added to the standard preoperative work-up and may even hold a potential to replace the ECS in a subgroup of patients with epilepsy who have the suspected epileptogenic zone near the sensorimotor cortex and seizures frequent enough for ictal MEG.

Bilateral changes in excitability of sensorimotor cortices during unilateral movement: combined electroencephalographic and transcranial magnetic stimulation study.

It remains unclear what neuronal mechanisms in humans are reflected in the activation of the ipsilateral hemisphere during the performance of unilateral movements. To address this question we combined transcranial magnetic stimulation (TMS), electroencephalography (EEG), and electromyographic (EMG) recordings of motor evoked potentials (MEPs). Compared with previous TMS studies, where changes in excitability might be related to both cortical and spinal mechanisms, our setup allowed a more direct evaluation of the cortical processes related to the performance of unilateral movements. EEG responses showed that the unilateral motor reactions were associated with the bilateral increase in the excitability of sensorimotor cortices. However, this increase was smaller in the ipsilateral hemisphere most likely due to the fact that the excitation in ipsilateral hemisphere coincided with additional inhibitory processes related to the suppression of mirror movements. This explanation was further corroborated by showing that only contralateral changes in cortical excitability led to the increase in the amplitude of peripheral MEPs, while neuronal activation in the ipsilateral hemisphere was not associated with the changes in the muscle responses. These results suggest that the increased excitability in the ipsilateral hemisphere was uncoupled from the modulation of the cortico-spinal output. Moreover, we show that the background neuronal activity during unilateral movements was different in the ipsi- and contralateral hemisphere. This difference most likely reflects inter-hemispheric balance between the excitation and inhibition which is required for the optimal performance of the unilateral movement.

How to include the variability of TMS responses in simulations: a speech mapping case study.

When delivered over a specific cortical site, TMS can temporarily disrupt the ongoing process in that area. This allows mapping of speech-related areas for preoperative evaluation purposes. We numerically explore the observed variability of TMS responses during a speech mapping experiment performed with a neuronavigation system. We selected four cases with very small perturbations in coil position and orientation. In one case (E) a naming error occurred, while in the other cases (NEA, B, C) the subject appointed the images as smoothly as without TMS. A realistic anisotropic head model was constructed of the subject from T1-weighted and diffusion-weighted MRI. The induced electric field distributions were computed, associated to the coil parameters retrieved from the neuronavigation system. Finally, the membrane potentials along relevant white matter fibre tracts, extracted from DTI-based tractography, were computed using a compartmental cable equation. While only minor differences could be noticed between the induced electric field distributions of the four cases, computing the corresponding membrane potentials revealed different subsets of tracts were activated. A single tract was activated for all coil positions. Another tract was only triggered for case E. NEA induced action potentials in 13 tracts, while NEB stimulated 11 tracts and NEC one. The calculated results are certainly sensitive to the coil specifications, demonstrating the observed variability in this study. However, even though a tract connecting Broca's with Wernicke's area is only triggered for the error case, further research is needed on other study cases and on refining the neural model with synapses and network connections. Case- and subject-specific modelling that includes both electromagnetic fields and neuronal activity enables demonstration of the variability in TMS experiments and can capture the interaction with complex neural networks.

Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: evidence of tumor-induced plasticity.

OBJECTIVE: This article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients. METHODS: Fifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5-10 Hz and 80-120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation. RESULTS: In healthy volunteers, language disturbances were almost exclusively induced in the left hemisphere. In patients errors were more frequent and induced at a comparative rate over both hemispheres. Predominantly dysarthric errors were induced in volunteers, whereas semantic errors were most frequent in the patient group. CONCLUSION: The right hemisphere's increased sensitivity to rnTMS suggests reorganization in language representation in brain tumor patients. SIGNIFICANCE: rnTMS is a novel technology for exploring cortical language representation. This study proves the feasibility and safety of rnTMS in patients with brain tumor.