study-design-for-navigated-repetitive-transcranial-magnetic

Study Design for Navigated Repetitive Transcranial Magnetic Stimulation for Speech Cortical Mapping

The cortical areas involved in human speech should be characterized reliably prior to surgery for brain tumors or drug-resistant epilepsy. The functional ...

Aalto University School of Science

University of Helsinki, Aalto University, and Helsinki University Hospital

University of Helsinki and Helsinki University Hospital

Cerebral palsy (CP) is characterized by difficulty in control of movement and posture due to brain damage during early development. In addition, tactile discrimination deficits are prevalent in CP. To study the function of somatosensory and motor systems in CP, we compared the reactivity of sensorimotor cortical oscillations to median nerve stimulation in 12 hemiplegic CP children vs. 12 typically developing children using magnetoencephalography. We also determined the primary cortical somatosensory and motor representation areas of the affected hand in the CP children using somatosensory-evoked magnetic fields and navigated transcranial magnetic stimulation, respectively. We hypothesized that the reactivity of the sensorimotor oscillations in alpha (10 Hz) and beta (20 Hz) bands would be altered in CP and that the beta-band reactivity would depend on the individual pattern of motor representation. Accordingly, in children with CP, suppression and rebound of both oscillations after stimulation of the contralateral hand were smaller in the lesioned than intact hemisphere. Furthermore, in two of the three children with CP having ipsilateral motor representation, the beta- but not alpha-band modulations were absent in both hemispheres after affected hand stimulation suggesting abnormal sensorimotor network interactions in these individuals. The results are consistent with widespread alterations in information processing in the sensorimotor system and complement current understanding of sensorimotor network development after early brain insults. Precise knowledge of the functional sensorimotor network organization may be useful in tailoring individual rehabilitation for people with CP.

Reactivity of sensorimotor oscillations is altered in children with hemiplegic cerebral palsy: A magnetoencephalographic study.

To assess the inter-hemispheric differences in neuronal function and structure of the motor cortex in a small group of chronic stroke patients having suffered a restricted ischemic lesion affecting hand motor representation. GABAergic intracortical inhibition, known to be affected by stroke lesion, was also investigated.

Functional and structural cortical characteristics after restricted focal motor cortical infarction evaluated at chronic stage - Indications from a preliminary study.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) enables one to study effective connectivity and activation order in neuronal networks. To characterize effective connectivity originating from the primary motor cortex (M1), dorsal premotor area (PMd), and supplementary motor area (SMA). Three right-handed volunteers (two men, aged 25-30 years) participated in a navigated TMS-EEG experiment. M1, PMd, and SMA over the nondominant hemisphere were stimulated with 150 TMS pulses. Minimum-norm estimates were derived from the EEG data to estimate the spatial spreading of TMS-elicited neuronal activation on an individual level. The activation order of the cortical areas varied depending on the stimulated area. There were similarities and differences in the spatial distribution of the TMS-evoked potentials between subjects. Similarities in cortical activation patterns were seen at short poststimulus latencies and the differences at long latencies. This pilot study suggests that cortical activation patterns and the activation order of motor areas differ interindividually and depend on the stimulated motor area. It further indicates that TMS-activated effective connections or underlying structural connections vary between subjects. The spatial patterns of TMS-evoked potentials differ between subjects especially at long latencies, when probably more complex neuronal networks are active.

Individual Activation Patterns After the Stimulation of Different Motor Areas: A Transcranial Magnetic Stimulation-Electroencephalography Study.

Chronic neuropathic pain is known to alter the primary motor cortex (M1) function. Less is known about the normal, physiological effects of experimental neurogenic pain on M1. The objective of this study is to determine how short-interval intracortical inhibition (SICI) is altered in the M1 representation area of a muscle exposed to experimental pain compared to SICI of another muscle not exposed to pain. The cortical representation areas of the right abductor pollicis brevis (APB) and biceps brachii (BB) muscles of 11 subjects were stimulated with a multi-locus transcranial magnetic stimulation device while the resulting motor-evoked potentials (MEPs) were recorded with electromyography. Single- and paired-pulse TMS was administered in seven conditions, including one with the right hand placed in cold water. The stimulation intensity for the conditioning pulses in the paired-pulse examination was 80% of the resting motor threshold (RMT) of the stimulated site and 120% of RMT for both the test and single pulses. The paired-pulse MEP amplitudes were normalized with the mean amplitude of the single-pulse MEPs of the same condition and muscle. SICI was compared between conditions. After the cold pain, the normalized paired-pulse MEP amplitudes decreased in APB, but not in BB, indicating that SICI was potentially increased only in the cortical area of the muscle subjected to pain. These data suggest that SICI is increased in the M1 representation area of a hand muscle shortly after exposure to pain has ended, which implies that short-lasting pain can alter the inhibitory balance in M1.

The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation.

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is commonly applied for studying the effective connectivity of neuronal circuits. The stimulation excites neurons, and the resulting TMS-evoked potentials (TEPs) are recorded with EEG. A serious obstacle in this method is the generation of large muscle artifacts from scalp muscles, especially when frontolateral and temporoparietal, such as speech, areas are stimulated. Here, TMS-EEG data were processed with the signal-space projection and source-informed reconstruction (SSP-SIR) artifact-removal methods to suppress these artifacts. SSP-SIR suppressed muscle artifacts according to the difference in frequency contents of neuronal signals and muscle activity. The effectiveness of SSP-SIR in rejecting muscle artifacts and the degree of excessive attenuation of brain EEG signals were investigated by comparing the processed versions of the recorded TMS-EEG data with simulated data. The calculated individual lead-field matrix describing how the brain signals spread on the cortex were used as simulated data. We conclude that SSP-SIR was effective in suppressing artifacts also when frontolateral and temporoparietal cortical sites were stimulated, but it may have suppressed also the brain signals near the stimulation site. Effective connectivity originating from the speech-related areas may be studied even when speech areas are stimulated at least on the contralateral hemisphere where the signals were not suppressed that much.

EEG Artifact Removal in TMS Studies of Cortical Speech Areas.

The combination of transcranial magnetic stimulation and electroencephalography can be applied to probe effective connectivity. Neurons are excited by magnetic pulses, which produce transcranial magnetic stimulation-evoked potentials that can be monitored with electroencephalography. Effective connectivity refers to causal connections in the brain; it describes how different brain areas communicate with each other. Broca's area is crucial for all phases of speech processing and is located in the frontotemporal region of the cortex. Only a few studies have investigated this region using transcranial magnetic stimulation-electroencephalography because of the large cranial muscles that are located over these areas, resulting in large artifacts covering the transcranial magnetic stimulation-evoked potentials. However, it is shown that this obstacle can be overcome with new artifact-removal tools. We used minimum-norm estimation to locate the sources of the neuronal signals in electroencephalography data after stimulating the right-hemispheric homologue of Broca's area in three right-handed subjects; it was shown that the spreading of brain activity might be different for different individuals and that the brain activity spread fast to the contralateral hemisphere.

Transcranial magnetic stimulation-evoked potentials after the stimulation of the right-hemispheric homologue of Broca's area.

There is no effective evidence-based non-pharmacological treatment for severe neuropathic pain after spinal cord injury (SCI). Paired associative stimulation (PAS) has been used in motor rehabilitation of patients after SCI. In the SCI-PAS protocol for tetraplegic patients, peripheral and central nerve tracts are activated with subject-specific timing, such that ascending and descending signals appear simultaneously at the cervical level. The effect on motor rehabilitation is thought to arise via strengthening of cervical upper and lower motoneuron synapses. We have observed an analgesic effect of PAS on mild-to-moderate neuropathic pain in tetraplegic patients receiving PAS for motor rehabilitation. Here, we applied PAS to a patient with severe drug-resistant neuropathic pain.

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report.

Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.

A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial.

Transcranial magnetic stimulation (TMS) induces an electric field (E-field) in the cortex. To facilitate stimulation targeting, image-guided neuronavigation systems have been introduced. Such systems track the placement of the coil with respect to the head and visualize the estimated cortical stimulation location on an anatomical brain image in real time. The accuracy and precision of the neuronavigation is affected by multiple factors. Our aim was to analyze how different factors in TMS neuronavigation affect the accuracy and precision of the coil-head coregistration and the estimated E-field.By performing simulations, we estimated navigation errors due to distortions in magnetic resonance images (MRIs), head-to-MRI registration (landmark- and surface-based registrations), localization and movement of the head tracker, and localization of the coil tracker. We analyzed the effect of these errors on coil and head coregistration and on the induced E-field as determined with simplistic and realistic head models.Average total coregistration accuracies were in the range of 2.2-3.6 mm and 1°; precision values were about half of the accuracy values. The coregistration errors were mainly due to head-to-MRI registration with average accuracies 1.5-1.9 mm/0.2-0.4° and precisions 0.5-0.8 mm/0.1-0.2° better with surface-based registration. The other major source of error was the movement of the head tracker with average accuracy of 1.5 mm and precision of 1.1 mm. When assessed within an E-field method, the average accuracies of the peak E-field location, orientation, and magnitude ranged between 1.5 and 5.0 mm, 0.9 and 4.8°, and 4.4 and 8.5% across the E-field models studied. The largest errors were obtained with the landmark-based registration. When computing another accuracy measure with the most realistic E-field model as a reference, the accuracies tended to improve from about 10 mm/15°/25% to about 2 mm/2°/5% when increasing realism of the E-field model.The results of this comprehensive analysis help TMS operators to recognize the main sources of error in TMS navigation and that the coregistration errors and their effect in the E-field estimation depend on the methods applied. To ensure reliable TMS navigation, we recommend surface-based head-to-MRI registration and realistic models for E-field computations.

Article	Year
Reactivity of sensorimotor oscillations is altered in children with hemiplegic cerebral palsy: A magnetoencephalographic study. Human brain mapping\| PubMed ID: 24522997	2014
Functional and structural cortical characteristics after restricted focal motor cortical infarction evaluated at chronic stage - Indications from a preliminary study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology\| PubMed ID: 27417053	2016
Individual Activation Patterns After the Stimulation of Different Motor Areas: A Transcranial Magnetic Stimulation-Electroencephalography Study. Brain connectivity\| PubMed ID: 30152705	2018
The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation. Experimental brain research\| PubMed ID: 30919012	2019
EEG Artifact Removal in TMS Studies of Cortical Speech Areas. Brain topography\| PubMed ID: 31290050	2020
Transcranial magnetic stimulation-evoked potentials after the stimulation of the right-hemispheric homologue of Broca's area. Neuroreport\| PubMed ID: 31568206	2019
Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report. Scandinavian journal of pain\| PubMed ID: 34019752	2021
A Randomized, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial. Neuromodulation : journal of the International Neuromodulation Society\| PubMed ID: 35670063	2022
Accuracy and precision of navigated transcranial magnetic stimulation. Journal of neural engineering\| PubMed ID: 36541458	2022

Selja Vaalto

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