Selja Vaalto

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

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. Hum Brain Mapp 35:4105–4117, 2014.

Corticospinal Output and Cortical Excitation-Inhibition Balance in Distal hand Muscle Representations in Nonprimary Motor Area

Transcranial magnetic stimulation (TMS) of the superior frontal gyrus in the non‐primary motor area (NPMA) can evoke motor‐evoked potentials (MEPs) at 20 ms latency range in contralateral distal hand muscles similar to stimulation of M1 and indicating monosynaptic corticospinal tracts. We compared the intracortical inhibitory and excitatory balance in primary motor cortex (M1) and in NPMA by navigated single‐ and paired‐pulse TMS (ppTMS). We also evaluated the spatial stability of muscle representations in M1 and NPMA by remapping 11 healthy subjects one year after the initial mapping. Resting motor threshold (rMT) was higher in NPMA than in M1 as were the MEP amplitudes evoked by 120% rMT stimulation intensity of the local MT. Short‐interval intracortical inhibition (SICI) was significantly weaker in NPMA than in M1 at ISI of 2 ms and conditioning stimulus (CS) 80% rMT. Our findings suggest that the cortical hand representations in NPMA 1) are connected to lower motoneurons monosynaptically, 2) are less strictly organized, i.e. motoneuron population representing a discrete hand muscle is sparser and less dense than in M1 and 3) have the capacity to generate powerful, rapid muscle contraction if sufficient number of motoneurones are activated. In NPMA, local intracortical inhibitory and excitatory activity is mainly similar to that in M1. The lower SICI in NPMA at an ISI of 2 ms may reflect less strict topographic organization and readiness to reorganization of neural circuits during motor learning or after motor deficits. Hum Brain Mapp, 2010.

Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report

IntroductionNavigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value.MethodsThe nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications.ResultsnTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here.ConclusionAt present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.

Long-term plasticity may be manifested as reduction or expansion of cortical representations of actively used muscles in motor skill specialists

Our aim was to study long-term plasticity in the organization of cortical muscle representations due to extensive motor training for different skills. We were especially interested in whether skill-specific demands on independent hand muscle movements and synchronous leg muscle movements are reflected differently in the reorganization of muscle representations. We used navigated transcranial magnetic stimulation to estimate the size of cortical representations of opponens pollicis, abductor digiti minimi, and tibialis anterior muscles in five string instrument players, five figure skaters, and five controls. The extent of the representation area was presented as an amplitude-area curve showing the spatial distribution of motor evoked potentials. The size of representation areas was compared between the dominant and nondominant hemispheres and between the groups. The representation area of the left abductor digiti minimi (critical for reaching right tones) in the right, nondominant hemisphere was smaller in string players and the representation area of the tibialis anterior in the dominant hemisphere (critical for jumps) was larger in figure skaters when compared with controls. Reorganization in the motor cortex may differ depending upon the skill and an individual muscle’s role in the skill. A smaller representation area of the independently used hand muscle in masters of fine motor skills may reflect long-term plasticity toward more focused representation, which may be beneficial in accurate and discrete cortical control of the muscle. Larger cortical representations are related to skill demanding coactivation of proximal and distal lower limb muscles.

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

OBJECTIVE 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. METHODS Eight patients exhibiting little or no motor impairment were studied using transcranial magnetic stimulation (TMS) and diffusion weighted imaging (DWI) >15months from diagnosis. Resting motor threshold (MT) for 50μV and 2mV motor evoked potentials, and short-interval intracortical inhibition (SICI) were measured from hand muscles. Apparent diffusion coefficients (ADCs) were analyzed from the DWI for the primary motor cortex (M1), the supplementary motor area (SMA) and thalamus for reflecting changes in neuronal organization. RESULTS The MTs did not differ between the affected (AH) and unaffected hemisphere (UH) in 50μV responses, while the MTs for 2mV responses were higher (p=0.018) in AH. SICI was weakened in AH (p=0.008). ADCs were higher in the affected M1 compared to the unaffected M1 (p=0.018) while there were no inter-hemispheric differences in SMA or thalamus. CONCLUSIONS Inter-hemispheric asymmetry and neuronal organization demonstrated abnormalities in the M1. However, no confident inference can be made whether the observed alterations in neurophysiological and imaging measures have causal role for motor rehabilitation in these patients. SIGNIFICANCE Neurophysiological changes persist and are detectable using TMS years after stroke even though clinical symptoms have normalized.

P22.17 Cortical reorganization differs depending on the nature of the motor skill

the execution of an implicit learning paradigm, the serial reaction time task (SRTT). Methods: During the SRTT stimuli appear at predefined locations of a computer screen to which the subjects have to respond as fast and accurate as possible. The appearance of the stimuli follows a predefined, but not apparently recognizable sequence in a repeating pattern. Seventeen subjects participated in the study in a repeated measurements design, with a minimum of four days between the sessions. MEP responses from the first dorsal interosseous (FDI) and forearm flexor (FLEX) muscles were measured before, during and after performance of the SRTT. Online measurements were combined with anodal, cathodal or sham tDCS (1 mA, FDI hot-spot contralateral orbit montage) during the SRTT. Results: MEPs recorded from the FDI muscle tended to be higher in the active stimulation conditions, compared to the sham condition; with a significant increase in the cathodal condition. A difference has also been observed between the two active conditions in MEPs elicited from the forearm FLEX muscles in the initial learning phase, with higher MEP values evoked during cathodal stimulation. The most pronounced decrease in reaction time during the SRTT task was found in the anodal condition which indicates facilitated implicit learning performance in this condition. Conclusions: This is the first time that online recording of TMS-elicited MEPs have been measured during the performance of a sequential reaction time task whilst demonstrating implicit motor learning, and it may give an insight into how tDCS modulates implicit learning during the acquisition and consolidation phases.

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

BACKGROUND The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) enables one to study effective connectivity and activation order in neuronal networks. OBJECTIVE To characterize effective connectivity originating from the primary motor cortex (M1), dorsal premotor area (PMd), and supplementary motor area (SMA). METHODS Three right-handed volunteers (2 males, aged 25-30) participated in a navigated TMS-EEG experiment. M1, PMd, and SMA over the non-dominant hemisphere were stimulated with 150 TMS pulses. Minimum-norm estimates (MNE) were derived from the EEG data to estimate the spatial spreading of TMS-elicited neuronal activation on an individual level. RESULTS 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. The similarities in cortical activation patterns were seen at short post-stimulus latencies and the differences at long latencies. CONCLUSIONS This pilot study suggests that cortical activation patterns and the activation order of motor areas differ inter-individually 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.Abstract The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) enables one to study effective connectivity and activation order in neuronal networks. To charac...

O152 Investigating effective connectivity in the motor network with TMS-evoked cortical potentials

Objectives Our purpose was to learn what the spatial distribution of transcranial magnetic stimulation (TMS)-evoked potentials can reveal about connectivity originating from premotor, supplementary, and primary motor cortices. Methods The data were collected with the combination of navigated TMS (nTMS) and EEG from four subjects (one subject reported here). The primary, pre-, and supplementary motor cortices in both hemispheres were stimulated, each area receiving 150 pulses at stimulation intensity of 90% of the electric field of ipsilateral APB motor threshold. The EEG datasets were preprocessed with novel artifact-removal algorithms (Mutanen et al., NeuroImage 2016). The first four peaks and their latencies were determined from the global mean field amplitudes (GMFA). At these peak latencies, minimum-norm estimates (MNE) indicated sites of most prevalent cortical activity. Results The new artifact-removal method proved to be useful as the first step in the data analysis. The spreading of neuronal activity depends on the stimulation target; the order of the activated cortical areas varies when different motor-related areas are stimulated. Discussion Our combination of experimental settings, data processing tools, and data-analysis methods can be used to evaluate effective connections from motor areas. Cortical activation patterns differ depending on the stimulated motor area. Conclusions nTMS–EEG can be used to investigate the connectivity originating from motor areas. Significance nTMS–EEG may be used to select stimulation sites on the cortex when specific neuronal connections should be strengthened by TMS, for example, in stroke patients.

Increased Inhibition in Non-Primary Motor Areas of String-Instrument Players: A Preliminary Study with Paired-Pulse Transcranial Magnetic Stimulation

Background: The muscle representations in non-primary motor area (NPMA) are located in the dorsal premotor area (PMd) and in the border region between the premotor area and the supplementary motor area (SMA). Objective: We characterized the plasticity of intracortical inhibitory and excitatory circuits in muscle representations in primary motor cortex (M1) and in NPMA related to acquired fine motor skills. We compared local cortical inhibition and facilitation balance in M1 and in NPMA between control subjects (n = 6) and right-handed string-instrument players (n = 5). Methods: Navigated transcranial magnetic stimulation (TMS) was used to compare motor thresholds (MTs), motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in non-dominant hand muscle representations in M1 and NPMA. Results: String-instrument players showed reduced SICI in M1 in the actively used left hand abductor digiti minimi (ADM) muscle representation at 3 ms inter-stimulus interval (ISI) with a conditioning stimulus (CS) intensity of 80% of MT and increased SICI in NPMA in ADM representation at 2 ms ISI and CS intensity of 50% of MT in comparison with controls. No differences between string-instrument players and controls were found for the SICI in the left hand opponens pollicis (OP) muscle representation, which is a muscle not intensively trained in string-instrument players. Conclusions: These preliminary results indicate that the stronger inhibition in motor representations outside M1 in string-instrument players may be crucial when accurate movements of single muscles must be performed. In contrast, weaker inhibition in M1 in string-instrument players may benefit the performance of fast finger movements.

OP28 – 2809: Structural MRI, transcranial magnetic stimulation, magnetoencephalography and DTI tractography findings in relation to sensorimotor outcome after perinatal stroke

Objective Despite the frequency and importance of sensorimotor deficits after perinatal stroke (PS), the correlation between brain damage and severity of hemiparesis remains unclear. We aimed to investigate inter-relations between stroke topography, (re)organization of motor and sensory pathways, and clinical grade of hemiparesis in children with PS. Methods Seven children (3 boys; age 12–18 years) with mild to profound upper limb impairment (MACS I-V) after left-sided PS were enrolled. 3T structural MRI scans were reviewed to define vascular origin and extent of the infarction. Information about gestational age, delivery, and type of presentation, were collected from patient records. Navigated transcranial magnetic stimulation (nTMS) was used to map cortical hand muscle representations. The integrity of thalamocortical pathways was evaluated with somatosensory evoked magnetic fields to electrical median nerve stimulation and tractography based on regions of interest defined by neuroradiologist. Asymmetry of tract volume (TV), tract mean fractional anisotropy and mean diffusivity (MD) were estimated. Somatosensory responses were assessed by Semmes-Weinstein monofilaments. Results In two children with unilateral truncal middle cerebral artery (MCA) infarctions, moderate to severe hemiparesis (MACS II-III; sensory deficits in one) was associated with ipsilateral motor and contralateral somatosensory representation of the paretic hand. In a child with proximal MCA stroke, profound hemiplegia with sensory impairment (MACS V) was found in relation to purely contralateral motor and somatosensory projections, distinguished by decreased ipsilesional thalamocortical TV and increased MD in comparison to other subjects. While MEG showed contralateral somatosensory representation in four children with periventricular venous infarctions, who had less severe hemiparesis (MACS I-II, no sensory deficits), nTMS revealed bilateral motor representation. Conclusion Distinct (re)organization patterns after different subtypes of PS are demonstrated by modern neuroimaging techniques, which complement structural MRI in the prediction of severity of hemiparesis after PS.