1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson’s disease: effects on bradykinesia of arm and hand

To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson’s disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.     

The effects of 1 Hz rTMS over the hand area of M1 on movement kinematics of the ipsilateral hand

1 Hz rTMS applied over primary motor cortex (M1) reduces cortical excitability outlasting the stimulation period. Healthy right-handed subjects performed finger and hand tapping and a reach-to-grasp movement prior to (baseline) and after 1 Hz rTMS applied over (1) M1 of either the right or the left hemisphere, and (2) the vertex (control stimulation). 1 Hz rTMS applied over the left M1, but not over the vertex, improved movement kinematics of finger and hand tapping as well as grasping with the left hand. 1 Hz rTMS applied over the right M1, but not over the vertex, improved only the kinematics of hand tapping performed with the right hand. These data suggest that 1 Hz rTMS induced inhibition of ipsilateral M1 reduces transcallosal inhibition of contralateral M1 and thereby improves motor performance at the ipsilateral hand. The impact on motor performance of the ipsilateral hand is most pronounced after 1 Hz rTMS over the left M1.     

Effects of movement on somatosensory N20m fields and high-frequency oscillations

Somatosensory evoked fields were recorded to determine the effects of movement and attention on high-frequency oscillations during active finger movements of the ipsilateral and contralateral sides in response to electrical stimulation of the median nerve. A whole-scalp neuromagnetometer was used to record somatosensory evoked fields from eight subjects following electric median nerve stimulation at the wrist. The following three sessions were performed: (1). rest, (2). movement of fingers on the ipsilateral in response to stimulation and (3). movement of fingers on the contralateral in response to stimulation. The somatosensory evoked fields with a wide-bandpass (0.1-1000 Hz) were recorded. High-frequency oscillations and N20m were separated by subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. The maximum amplitude of high-frequency oscillations decreased during finger movements accompanying a decrease in somatosensory N20m dipole strength. Activation of the motor cortex appeared to suppress both the amplitude of high-frequency oscillations and the N20m dipole strength.     

Short latency mechanically evoked somatosensory potentials in humans.

Somatosensory potentials evoked by mechanical stimulation were recorded by surface electrodes over (1) the digital nerves in the index finger, (2) the median nerve at the wrist, (3) the median nerve near the axilla, (4) the brachial plexus, (5) the cervical cord at CII, (6) the scalp overlying the somatosensory cortex. Nerve conduction velocities varied inversely with age and ranged from 43 to 68 m/sec. Mechanically evoked potentials recorded from the electrodes overlying the digital nerves were an artifact of the finger movement. All other electrode configurations recorded potentials comparable to those evoked by electrical stimulation of nerves. These mechanically evoked potentials could prove useful in the assessment of clinical disorders of somatosensory function from receptor to cortex in man.     

Somatosensory evoked potentials after median and tibial nerve stimulation in healthy newborns.

Cortical and spinal somatosensory evoked potentials (SEPs) have been recorded after median and tibial nerve stimulation in healthy newborns. Spinal SEPs were readily obtained and recorded in all but one neonates after stimulation of both nerves. Cortical SEPs were more frequently recorded after median nerve (87%) than after tibial nerve stimulation (73%) but the shape of cortical SEPs obtained after tibial nerve stimulation was less variable. The mean feature of cortical SEPs was a negative wave (N27) for median nerve and a positive wave (P32) for tibial nerve. The present results demonstrate the feasibility of obtaining in the same baby, spinal and cortical SEPs after stimulation of median and tibial nerve, giving information on the functional integrity of central and peripheral somatosensory pathways which supply upper and lower limbs.     

Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor

The cerebellum is involved in the generation of essential tremor (ET) and cerebellar timing function is altered in patients with ET showing an increased variability of rhythmic hand movements. Using a sensor‐engineered glove, we evaluated motor behaviour during repetitive finger tapping movements in 15 patients with ET and in 11 age‐ and gender‐matched normal subjects. In addition, we investigated whether, in patients with ET, an inhibitory repetitive transcranial magnetic stimulation (1 Hz‐rTMS) over lateral cerebellum was able to change timing properties and motor behaviour. Patients with ET showed a longer touch duration (TD) and a lower inter tapping interval (ITI) than normal subjects. The temporal variability of the movement (coefficient of variation of ITI) was increased in patients with ET. Neither clinical rating scale or tremor measurements correlated with any parameter of motor performance in the ET group. 1 Hz‐rTMS over ipsilateral lateral cerebellum transiently affected the performance of patients with ET, by reducing TD values and normalizing ITI values. After 1 Hz‐rTMS, the coefficient of variation of ITI was restored to values similar to those of normal subjects. We postulate that the strategy to increase TD, probably adopted to allow a better perception of movement, can affect ITI and its variability. The results support the idea that the cerebellum plays a central role in the selection of motor strategy of rhythmic finger movements, particularly in terms of temporal organization of movement.     

Length dependence of variables associated with temporal dispersion in human motor nerves

Temporal dispersion in motor nerves is associated with changes of amplitude, area, duration, and Fourier spectra of compound muscle action potentials (CMAPs) when comparing responses to proximal and distal stimulation. These changes depend on the length of the nerve segment. To quantitatively assess this dependence, motor conduction studies of nerve segments of various lengths were performed in the median, ulnar, and tibial nerves of 86 test subjects, aged 4 to 73 years. Amplitude, area, duration, and spectral energy above 49 Hz of CMAPs were measured. Values after distal and proximal stimulation of each nerve segment were compared to determine amplitude decay, area decay, protraction, and high-frequency attenuation. A significant length dependence of amplitude decay was found in the tibial and ulnar nerves, of area decay in the median and ulnar nerves, and of CMAP duration in the ulnar and tibial nerves. The length dependence of the high-frequency attenuation was significant in all nerves studied. This report provides normative data for variables associated with temporal dispersion.     

Origin of the early components of somatosensory evoked potentials by the posterior tibial nerve stimulation--a comparative study of median nerve stimulation in clinical cases

In order to determine the generation sites of short latency somatosensory evoked potentials to the posterior tibial nerve stimulation, scalp topography was performed on 10 normal subjects in the two different band-pass recordings, i.e., wide band-pass filter (5-3000 Hz) and narrow band-pass filter (100-1000 Hz). Furthermore, comparative study of the changes of evoked potentials between posterior tibial nerve stimulation and median nerve stimulation was carried out in 22 cases with well localized lesion of the central nervous system in the same wide band-pass filter setting. The early components of somatosensory evoked potentials elicited by the posterior tibial nerve stimulation were obtained as P 30, N 34, and P 38 in the wide band-pass filter, and P 29, N 32, P 36 in the narrow band-pass filter. Components P 30, N 34 and components P 29, N 32 were widely distributed on the scalp, but were disappeared on the scalp-scalp recording. These results suggested all those components were generated from the deep subcortical structures. In the case with high cervical lesion, component P 30 at the posterior tibial nerve stimulation was remarkably prolonged in latency, and component P 13 at the median nerve stimulation was disappeared. P 30-N 34 interpeak latency at the posterior tibial nerve stimulation was prolonged in the case with pontine lesion, while P 13-N 16 interpeak latency at the median nerve stimulation was also prolonged. In the cases with thalamic and internal capsular lesion, P 30 and N 34 at the posterior tibial nerve stimulation and P 13 and N 16 at the median nerve stimulation were all preserved in normal range. These results revealed that components P 30 and N 34 were almost identical to components P 13 and N 16, respectively. On the other hand, component P 38 at the posterior tibial nerve stimulation was suppressed or disappeared in the cases with well localized lesion at the midcentro parietal region, that includes the primary foot sensory area.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanical flutter stimulation induces a lasting response in the sensorimotor cortex as revealed with BOLD fMRI

It has been recently shown that 20 min of mechanical flutter stimulation induces lasting motor cortical excitability changes, as assessed by transcranial magnetic stimulation in relaxed hand muscles. The present functional magnetic resonance imaging (fMRI) study aims to examine if such neuromodulatory changes are reflected in the BOLD signal during a motor test. Therefore, two groups were recruited: one group receiving whole‐hand flutter stimulation with a frequency of 25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM group, n = 22). As motor test finger‐to‐thumb tapping was performed to activate a wide sensorimotor network during the fMRI measurements. Three fMRI measurements were obtained with this test: before stimulation (PRE), after stimulation (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were defined: primary motor area (M1), primary somatosensory area (S1), and supplementary motor area. In the absence of baseline differences between both groups, the FSTIM group showed increased movement‐related brain activations compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed increased blood‐oxygenation‐level‐dependent (BOLD) responses within contralateral S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory effects within S1 and M1 obviously reflect neuroplastic changes associated with augmented cortical excitability. These findings are of high clinical relevance, for example, to improve the treatment of stroke patients. Hum Brain Mapp 34:2767–2774, 2013. © 2012 Wiley Periodicals, Inc.     

Sensorimotor interaction between somatosensory painful stimuli and motor sequences affects both anticipatory alpha rhythms and behavior as a function of the event side

It has been shown that concomitant painful stimulation and simple movement at the same hand is related to decreased anticipatory alpha event-related desynchronization (ERD) and reduced pain intensity, possibly due to the interference between somatosensory and motor information processing (Babiloni et al. [6]). Here, we tested the hypothesis that such interference also affects motor performance during sequential movements. Visual warning stimuli were followed by imperative stimuli associated to electrical painful stimulation at left or right middle finger; imperative stimuli triggered motor sequences with right index finger. Electroencephalographic data (N = 10, 128 electrodes) were spatially enhanced by surface Laplacian transformation. Cortical activity as revealed by the alpha event-related desynchronization (ERD) was compared in “Pain + ipsilateral movement” condition (movements and painful stimuli performed at the right hand) vs. “Pain + contralateral movement” condition (painful stimuli at left hand and movements performed at the right hand). Results showed that compared with the “Pain + contralateral movement” condition, the “Pain + ipsilateral movement” condition induced lower anticipatory alpha ERD (about 10–12 Hz) in left sensorimotor area, lower subjective pain rate, and delayed movement initiation at the group level. These findings suggest that anticipatory alpha rhythms may underlie cortical preparatory sensorimotor processes preceding somatosensory painful and the initiation of sequential motor events occurring at unilateral or bilateral hand.     

Carpal tunnel syndrome modifies sensory hand cortical somatotopy: a MEG study

The adult somatosensory system has shown reorganizational abilities at cortical and subcortical levels after peripheral nerve lesions. In the present study the effects of carpal tunnel syndrome (CTS) are investigated as reflected on the somatotopy of the primary cortical hand representation. Position and intensity of cortical sources activated by the separate electrical stimulation of median nerve and Digits 1, 3, and 5 of both affected and non-affected hands are evaluated by magnetoencephalographic (MEG) technique. Correlation of MEG results with patient-, physician- and neurophysiological-oriented evaluations of CTS was carried out. Patients showed changes in cortical hand somatotopy in strict relationship to self-referred assessment of symptoms and hand disability in daily activities, including: 1) a more extended representation of the affected hand when paresthesias prevailed; and 2) a more restricted representation due to lateral shift of the little finger was observed when pain symptoms dominated the clinical picture. Contralateral to the side of CTS, the cortical sources activated by Digit 5-stimulation appeared significantly enhanced with respect to contralateral ones from non-affected hand. When comparing the amplitude of peripheral sensory nerve action potentials of median and ulnar nerves to that of cortical responses (i.e., ECD strengths of M20 and M30 components after stimulation of Digits 3 and 5), a significant selective amplification of M30 with respect to M20 and sensory nerve action potential (SNAP) appeared during Digit 3 stimulation compared to that observed for Digit 5. This has been interpreted as a central magnification mechanism in brain responsiveness, possibly revealing a safety factor enabling sensory perception despite the small peripheral signal due to nerve trunk dysfunction. Hum.     

Difference in somatosensory evoked fields elicited by mechanical and electrical stimulations: Elucidation of the human homunculus by a noninvasive method

We recently recorded somatosensory evoked fields (SEFs) elicited by compressing the glabrous skin of the finger and decompressing it by using a photosensor trigger. In that study, the equivalent current dipoles (ECDs) for these evoked fields appeared to be physiologically similar to the ECDs of P30m in median nerve stimulation. We sought to determine the relations of evoked fields elicited by mechanically stimulating the glabrous skin of the great toe and those of electrically produced P40m. We studied SEFs elicited by mechanical and electrical stimulations from the median and tibial nerves. The orientations of dipoles from the mechanical stimulations were from anterior-to-posterior, similar to the orientations of dipoles for P30m. The direction of the dipole around the peak of N20m from median nerve electrical stimulation was opposite to these directions. The orientations of dipoles around the peak of P40m by tibial nerve stimulation were transverse, whereas those by the compression and decompression stimulation of the toe were directed from anterior-to-posterior. The concordance of the orientations in ECDs for evoked fields elicited by mechanical and electrical stimulations suggests that the ECDs of P40m are physiologically similar to those of P30m but not to those of N20m. The discrepancy in orientations in ECDs for evoked field elicited by these stimulations in the lower extremity suggests that electrical and compression stimulations elicit evoked fields responding to fast surface rubbing stimuli and/or stimuli to the muscle and joint.     

Influences of transcutaneous electrical stimulation of cutaneous and mixed nerves on subcortical and cortical somatosensory evoked potentials

Aim of this study was to assess whether transcutaneous electrical nerve stimulation (TENS) 'gates' somatosensory evoked potentials (EPs) peripherally or centrally, and which afferent fibres and sensory nuclei mediate this effect. The following waves were recorded after stimulation of the median nerve at the wrist or of the digital nerves of the index finger: N9, the cervical N11 and N13, the parietal P9, P11, P14, N18, N20, P22, P27, P40. When both median or digital nerve EPs were conditioned by TENS delivered to the median nerve, reduction in amplitude of N9, P14, N18 and later generated cortical waves was observed. To measure the central contribution to this decrease, unconditioned 'reference' EPs were evoked by stimulating with a current strength yielding an N9 potential of an amplitude equal to that obtained during TENS. In this case, the amplitude of P14, N18 and later cortical waves was significantly greater than during TENS. When both median or digital nerve EPs were conditioned by TENS delivered to the digital nerves, waves were only slightly affected. No effects were seen on the EPs elicited from the median or index finger digital nerves when TENS was administered to the contralateral median or digital nerves or to the ipsilateral middle finger. It is concluded that TENS gates the somatosensory volley, both at a peripheral level through a 'busy line-effect' on large afferent fibres, and centrally at the level of the cuneatus nucleus.     

The impact of subthalamic deep brain stimulation on bradykinesia of proximal and distal upper limb muscles in Parkinson's disease

Objective To assess the differential effects of bilateral deep brain stimulation of the subthalamic nucleus on proximal and distal muscle groups of the upper limb in Parkinson's disease. Methods Eight parkinsonian subjects with chronic bilateral stimulation of the subthalamic nucleus performed index finger tapping (differentially drawing upon distal arm muscles), horizontal pointing (differentially drawing upon proximal arm muscles) and a complex reach-to-grasp task with cubes of different sizes, which involved both proximal and distal arm muscles. An ultrasound based system was used for kinematic motion analysis. Subjects were investigated in two clinical conditions: on and off subthalamic nucleus stimulation. Clinical symptom severity was rated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore. Results Stimulation of the subthalamic nucleus improved the UPDRS motor subscore (68 %). Bradykinesia of index finger tapping and horizontal pointing were equally improved by subthalamic nucleus stimulation. In contrast, in a complex reach-tograsp task bradykinesia was differentially ameliorated for the grasp component. Conclusion The data suggest that bilateral stimulation of the subthalamic nucleus improves bradykinesia of both distal and proximal muscles of the arm and hand in Parkinson's disease; however, dependent upon task complexity proximal and distal movement components may be affected differentially. Kinematic motion analysis is an efficient tool to objectively evaluate the beneficial effects of subthalamic nucleus stimulation on dexterity in Parkinson's disease.     

Germline mosaicism of a novel mutation in lysosome-associated membrane protein-2 deficiency (Danon disease)

It has been proposed that somatosensory input in the form of peripheral nerve stimulation can influence functional measures of motor performance. We studied the effects of median nerve stimulation on pinch muscle strength (a function mediated predominantly by median nerve innervated muscles) in the affected hand of chronic stroke patients. A 2-hour period of median nerve stimulation elicited an increase in pinch strength that outlasted the stimulation period. The improvement in muscle strength correlated with stimulus intensity and was identified in the absence of motor training. These results suggest that somatosensory stimulation may be a promising adjuvant to rehabilitation of the motor deficits in stroke patients.     

Effects of observing normal and abnormal goal‐directed hand movements on somatosensory cortical activation

Existing evidence indicates the importance of observing correct, normal actions on the motor cortical activities. However, the exact neurophysiological mechanisms, particularly in the somatosensory system, remain unclear. This study aimed to elucidate the effects of observing normal and abnormal hand movements on the contralateral primary somatosensory (cSI), contralateral (cSII) and ipsilateral (iSII) secondary somatosensory activities. Experiment I was designed to investigate the effects of motor outputs on the somatosensory processing, in which subjects were instructed to relax or manipulate a small cube. Experiment II was tailored to examine the somatosensory responses to the observation of normal (Normal) and abnormal (Abnormal) hand movements. The subjects received electrical stimulation to right median nerve and magnetoencephalography (MEG) recordings during the whole experimental period. Regional cortical activation and functional connectivity were analyzed. Compared to the resting condition, a reduction in cSI and an enhancement of SII activation was found when subjects manipulated a cube, suggesting the motor outputs have an influence on the somatosensory responses. Further investigation of the effects of observing different hand movements showed that cSII activity was significantly stronger in the Normal than Abnormal condition. Moreover, compared with Abnormal condition, a higher cortical coherence of cSI‐iSII at theta bands and cSII‐iSII at beta bands was found in Normal condition. Conclusively, the present results suggest stronger activation and enhanced functional connectivity within the somatosensory system during the observation of normal than abnormal hand movements. These findings also highlight the importance of viewing normal, correct hands movements in the stroke rehabilitation.     

Comparison of somatosensory evoked high-frequency oscillations after posterior tibial and median nerve stimulation.

OBJECTIVE: We compared the high-frequency oscillations (HFOs) evoked by posterior tibial nerve (PTN) and median nerve (MN) stimulation. METHODS: Somatosensory evoked potentials (SEPs) were recorded with a filter set at 10-2000 Hz to right PTN and to right MN stimulation in 10 healthy subjects. The HFOs were obtained by digitally filtering the wide-band SEPs with a band-pass of 300-900 Hz. RESULTS: HFOs were recorded in 8 of the 10 subjects for PTN, and in all subjects for MN stimulation. The HFOs after both PTN and MN stimulation started approximately at or after the onset of the primary cortical response (P37 and N20) and ended around the middle of the second slope. HFO amplitudes and area after PTN stimulation were significantly smaller than those after MN stimulation. HFO duration after PTN stimulation was markedly longer than that after MN stimulation. However, HFO interpeak latencies did not differ between the two nerves. CONCLUSIONS: The present findings suggest that the HFOs after PTN and MN stimulation reflect a neural mechanism common to the hand and foot somatosensory cortex.     

Anticipatory cerebellar responses during somatosensory omission in man

The traditional view of cerebellum is a structure that modifies and synchronizes elements of motor performance. Recent evidence indicates that human cerebellum is involved in a wide range of nonmotor sensory and cognitive functions. A common feature in these diverse motor and nonmotor tasks may be the capacity of cerebellar neuronal circuits to process and anticipate sensory input with high temporal acuity. We present evidence supporting this hypothesis from measurements of the magnetic field at the scalp evoked by neuronal population activity in human cerebellum. Intermittent electrical stimulation of the finger and the median nerve elicited stimulus-locked cerebellar responses with oscillatory components at 6-12 Hz and 25-35 Hz. Sustained oscillatory activity followed random stimulus omissions, with initiation of cerebellar responses prior to the next overt stimulus. These responses indexed processing of temporal features of somatosensory input independent of motor performance or response. The refractory behavior of the responses suggested that a neuronal trace of the temporal pattern of somatosensory stimulation remained in cerebellar circuits for 2-4 s. The cerebellar activity elicited by violation of an established temporal pattern was enhanced when attention was directed to somatosensory stimuli, in concordance with recent imaging studies suggesting participation of cerebellum in attentional networks. The attentional enhancement of the cerebellar responses supports the salience of cerebellar activity in the processing of purely somatosensory input. The short-term maintenance of cerebellar templates for predictable sensory input may reflect a physiological substrate for fine-grained temporal tuning and optimization of performance in large-scale sensory and integrative systems.     

Effects of motor activity on the organization of primary somatosensory cortex

Recent studies have shown that adaptation of representational maps within the primary somatosensory cortex can be induced by task-related motor activity. Here, we explore the relationship between the complexity of the motor task and the extent of task-specific adaptation within the primary somatosensory cortex. We hypothesized that the extent of adaptation increases with the complexity of the motor task. Using neuromagnetic source imaging based on electrical stimulation of the thumb and ring finger, we demonstrate that cortical finger representations are more distant during performance of the pinch finger grip than in a rest condition. Our data suggest that somatosensory cortical maps undergo rapid modulation depending on the task-specific involvement of somatosensory feedback in movements.     

High-frequency transcutaneous electrical nerve stimulation (TENS) differentially modulates sensorimotor cortices: An MEG study

ObjectiveTranscutaneous electrical nerve stimulation (TENS) affects excitability of the central motor system as well as the somatosensory system. To determine whether TENS has influence on excitability in the sensorimotor cortices of TENS-treated finger muscle, we investigated magnetoencephalogram associated with voluntary, self-paced finger movement before and after TENS.MethodsHigh-frequency TENS was applied on the extensor digitorum muscle for 15 min. Subjects underwent alternate middle finger and thumb extension movements before and after the TENS. We recorded movement-related cortical magnetic field (MRCF) associated with TENS-treated middle finger movement and that from untreated thumb movement.ResultsThe current source for motor field (MF) was located in the pre-central motor cortex and anteriorly-oriented, and that for motor evoked field one (MEF1) was found in the post-central somatosensory cortex and posteriorly-oriented. The amplitude of MF for TENS-treated middle finger movement decreased but unchanged for untreated thumb movement after TENS. The amplitude of MEF1 decreased for either finger movement after TENS.ConclusionHigh-frequency TENS to the forearm muscle modulates excitability of the limited area of motor cortex but wider area of primary somatosensory cortex.SignificanceHigh-frequency TENS to the forearm muscle modulates excitability of the primary somatosensory cortex and motor cortex in a different manner.