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 mapping of language areas for surgical decision-making is usually done invasively by electrical direct cortical stimulation (DCS), which is used to identify the organization of the crucial cortical and subcortical structures within each patient. Accurate preoperative non-invasive mapping aids surgical planning, reduces time, costs, and risks in the operating room, and provides an alternative for patients not suitable for awake craniotomy. Non-invasive imaging methods like MRI, fMRI, MEG, and PET are currently applied in presurgical design and planning. Although anatomical and functional imaging can identify the brain regions involved in speech, they cannot determine whether these regions are critical for speech. Transcranial magnetic stimulation (TMS) non-invasively excites the cortical neuronal populations by means of electric field induction in the brain. When applied in its repetitive mode (rTMS) to stimulate a speech-related cortical site, it can produce speech-related errors analogous to those induced by intraoperative DCS. rTMS combined with neuronavigation (nrTMS) enables neurosurgeons to preoperatively assess where these errors occur and to plan the DCS and the operation to preserve the language function. A detailed protocol is provided here for non-invasive speech cortical mapping (SCM) using nrTMS. The proposed protocol can be modified to best fit the patient- and site-specific demands. It can also be applied to language cortical network studies in healthy subjects or in patients with diseases that are not amenable to surgery.

Health-related quality of life and anxiety levels among patients under surveillance for intraductal papillary mucinous neoplasm.

BACKGROUND: Because of the premalignant nature of intraductal papillary mucinous neoplasms (IPMNs), patients should undergo surveillance as long as they remain fit for surgery. This surveillance, with imaging and laboratory tests every 6 to 12 months, is expensive and may psychologically burden patients. This study aimed to determine the effects of IPMN surveillance on patients´ health-related quality of life (HRQoL) and anxiety levels. METHODS: We included a random subgroup of all IPMN patients undergoing a follow-up check-up at Helsinki University Hospital (HUH) between August 2017 and November 2018. Patients were asked to complete the 15D HRQoL and state-trait anxiety inventory (STAI) questionnaires just before and three months after an IPMN control. RESULTS: Among 899 patients in IPMN follow-up, 232 participated. The 15D HRQoL results showed differences in some IPMN patients' 15 analyzed dimensions compared to a sex- and age-standardized general population cohort, but the clinical relevance of these differences appear doubtful. We detected no significant difference in the anxiety levels determined using the STAI questionnaires before or three months after the IPMN control. CONCLUSION: Surveillance should be less harmful than the risk of disease. Among our patients, the recommended IPMN follow-up carried minimal negative impact on patients' HRQoL or anxiety levels. This result is important, because the number of patients under IPMN surveillance is rapidly increasing and the cancer risk among the majority of these patients remains small. TRIAL REGISTRATION: The Surgical Ethics Committee of Helsinki University Hospital approved this study (Dnro HUS 475/2017) and it was registered at ClinicalTrials.gov (NCT03131076) before patient enrollment began.

Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects.

Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called "high-PAS", induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as "minimal intensity required to produce F-responses". We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence ("baseline"). In addition, we applied this intensity at + 25%, - 25%, and - 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of "baseline" and "baseline - 25%" levels but not at + 25% or - 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.

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

OBJECTIVES: 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. MATERIALS AND METHODS: This prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control. RESULTS: We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17-20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. CONCLUSIONS: S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.

Effect of long-term paired associative stimulation on the modulation of cortical sensorimotor oscillations after spinal cord injury.

STUDY DESIGN: A prospective interventional case series. OBJECTIVES: To explore changes in the modulation of cortical sensorimotor oscillations after long-term paired associative stimulation (PAS) in participants with spinal cord injury (SCI). SETTING: BioMag Laboratory, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. METHODS: Five patients with chronic incomplete SCI received unilateral spinal PAS to upper limb for 16-22 days. Changes in the modulation of sensorimotor oscillations in response to tactile stimulus and active and imaginary hand movements were assessed with magnetoencephalography recorded before and after the intervention. RESULTS: PAS restored the modulation of sensorimotor oscillations in response to active hand movement in four patients, whereas the modulation following tactile stimulation remained unaltered. The observed change was larger in the hemisphere that received PAS and preceded the clinical effect of the intervention. CONCLUSIONS: Long-term spinal PAS treatment, which enhances the motor functions of SCI patients, also restores the modulation of cortical sensorimotor oscillations.

A novel paired associative stimulation protocol with a high-frequency peripheral component: A review on results in spinal cord injury rehabilitation.

In recent decades, a multitude of therapeutic approaches has been developed for spinal cord injury (SCI), but few have progressed to regular clinical practice. Novel non-invasive, cost-effective, and feasible approaches to treat this challenging condition are needed. A novel variant of paired associative stimulation (PAS), high-PAS, consists of non-invasive high-intensity transcranial magnetic stimulation (TMS) and non-invasive high-frequency electrical peripheral nerve stimulation (PNS). We observed a therapeutic effect of high-PAS in 20 patients with incomplete SCI with wide range of injury severity, age, and time since injury. Tetraplegic and paraplegic, traumatic, and neurological SCI patients benefited from upper- or lower-limb high-PAS. We observed increases in manual motor scores (MMT) of upper and lower limbs, functional hand tests, walking tests, and measures of functional independence. We also optimized PAS settings in several studies in healthy subjects and began elucidating the mechanisms of therapeutic action. The scope of this review is to describe the clinical experience gained with this novel PAS approach. This review is focused on the summary of our results and observations and the methodological considerations for researchers and clinicians interested in adopting and further developing this new method.

Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study.

Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at clinicaltrials.gov (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed ( R adj 2 = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.

Interictal magnetoencephalography in parietal lobe epilepsy - Comparison of equivalent current dipole and beamformer (SAMepi) analysis.

OBJECTIVE: To evaluate a novel analysis method (SAMepi) in the localization of interictal epileptiform magnetoencephalographic (MEG) activity in parietal lobe epilepsy (PLE) patients in comparison with equivalent current dipole (ECD) analysis. METHODS: We analyzed the preoperative interictal MEG of 17 operated PLE patients utilizing visual analysis and: (1) ECD with a spherical conductor model; (2) ECD with a boundary element method (BEM) conductor model; and (3) SAMepi - a kurtosis beamformer method. Localization results were compared between the three methods, to the location of the resection and to the clinical outcome. RESULTS: Fourteen patients had an epileptiform finding in the visual analysis; SAMepi detected spikes in 11 of them. A unifocal finding in both the ECD and in the SAMepi analysis was associated with a better chance of seizure-freedom (p = 0.02). There was no significant difference in the distances from the unifocal MEG localizations to the nearest border of the resection between the different analysis methods. CONCLUSIONS: Localizations of unifocal interictal spikes detected by SAMepi did not significantly differ from the conventional ECD localizations. SIGNIFICANCE: SAMepi - a novel semiautomatic analysis method - is useful in localizing interictal epileptiform MEG activity in the presurgical evaluation of parietal lobe epilepsy patients.

Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series.

OBJECTIVES: Long-term paired associative stimulation (PAS) is a non-invasive combination of transcranial magnetic stimulation and peripheral nerve stimulation and leads to improved hand motor function in individuals with incomplete traumatic tetraplegia. Spinal cord injuries (SCIs) can also be induced by neurological diseases. We tested a similar long-term PAS approach in patients with non-traumatic neurological SCI. METHODS: In this case series, five patients with non-traumatic tetraplegia received PAS to the weaker upper limb 3 to 5 times per week for 6 weeks. Patients were evaluated by manual muscle testing (MMT) before and immediately after the therapy and at the 1- and 6-month follow-ups. Patients were also evaluated for spasticity, hand mechanical and digital dynamometry, pinch test and Box and Block test. RESULTS: MMT values of all patients improved at all post-PAS evaluations. The mean ±â€¯standard error MMT increase was 1.44 ±â€¯0.37 points (p = 0.043) immediately after PAS, 1.57 ±â€¯0.4 points (p = 0.043) at the 1-month follow-up and 1.71 ±â€¯0.47 points (p = 0.043) at the 6-month follow-up. The pinch test, digital dynamometry and Box and Block test results also improved in all patients. CONCLUSIONS: Long-term PAS may be a safe and effective treatment for improving hand function in patients with non-traumatic tetraplegia. SIGNIFICANCE: This is the first report demonstrating the therapeutic potential of PAS for neurological SCI.

The use of electronic coil location control for focal magnetic stimulation at the cervical level.

BACKGROUND: Accurate re-positioning of the coil is challenging in magnetic stimulation at the cervical spinal level. The applicability of coil location control for this type of stimulation is unexplored. NEW METHOD: Utilizing a figure-of-eight coil and anatomy-specific models of the magnetic stimulation system, we developed a novel technique that enables probing corticospinal excitability at the cervical spinal level. Magnetic stimulation was performed in 9 healthy subjects at C2-C6 spinal levels using a figure-of-eight coil and a coil tracking system. MEPs were recorded from the abductor digiti minimi muscle. The functioning of the coil tracking system was tested with an estimated electric field maximum (eEFM) above the C1 cervical level (group 1) and below (group 2). Motor-evoked potential (MEP) reproducibility was assessed with intra-class correlation coefficient (ICC). RESULTS: The use of coil location control in cervical level focal magnetic stimulation enabled the recording of highly reproducible MEPs. Within one co-registration, the ICC 95% confidence interval (CI) in group 1 was 0.89-0.99 and in group 2 was 0.24-0.85. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: This method can be used for accurate maintenance and retrieval of the focal coil position at the cervical level with low spatial variability during stimulation. Existing methodologies employ determination of the coil location based on external landmarks, which makes the procedure cumbersome. This technique can optimize existing stimulation protocols and facilitate development of navigated spinal stimulation.

A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients.

OBJECTIVE: The intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG). METHODS: We recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and-from the vector sum of signals of this gradiometer pair-calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres. RESULTS: The laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003). SIGNIFICANCE: This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.

Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand.

A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS. Five patients (4 males; age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham's Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulation session. One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02 ± 0.17 points (p < 0.0001, n = 100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176 ± 29%, p = 0.046, n = 5 patients). Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients.

Emerging therapeutic strategies for spinal cord injury aim at sparing or restoring at least part of the corticospinal tract at the acute stage. Hence, approaches that strengthen the weak connections that are spared or restored are crucial. Transient plastic changes in the human corticospinal tract can be induced through paired associative stimulation, a noninvasive technique in which transcranial magnetic brain stimulation is synchronized with electrical peripheral nerve stimulation. A single paired associative stimulation session can induce transient plasticity in spinal cord injury patients. It is not known whether paired associative stimulation can strengthen neuronal connections persistently and have therapeutic effects that are clinically relevant. We recruited two patients with motor-incomplete chronic (one para- and one tetraplegic) spinal cord injuries. The patients received paired associative stimulation for 20-24 weeks. The paraplegic patient, previously paralyzed below the knee level, regained plantarflexion and dorsiflexion of the ankles of both legs. The tetraplegic patient regained grasping ability. The newly acquired voluntary movements could be performed by the patients in the absence of stimulation and for at least 1 month after the last stimulation session. In this unblinded proof-of-principle demonstration in two subjects, long-term paired associative stimulation induced persistent and clinically relevant strengthening of neural connections and restored voluntary movement in previously paralyzed muscles. Further study is needed to confirm whether long-term paired associative stimulation can be used in rehabilitation after spinal cord injury by itself and, possibly, in combination with other therapeutic strategies.

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation.

BACKGROUND: In spinal paired associative stimulation (PAS), orthodromic volleys are induced by transcranial magnetic stimulation (TMS) in upper motor neurons, and antidromic volleys by peripheral nerve stimulation (PNS) in lower motor neurons of human corticospinal tract. The volleys arriving synchronously to the corticomotoneuronal synapses induce spike time-dependent plasticity in the spinal cord. For clinical use of spinal PAS, it is important to develop protocols that reliably induce facilitation of corticospinal transmission. Due to variability in conductivity of neuronal tracts in neurological patients, it is beneficial to estimate interstimulus interval (ISI) between TMS and PNS on individual basis. Spinal root magnetic stimulation has previously been used for this purpose in spinal PAS targeting upper limbs. However, at lumbar level this method does not take into account the conduction time of spinal nerves of the cauda equina in the spinal canal. NEW METHOD: For lower limbs spinal PAS, we propose estimating appropriate ISIs on the basis of F-response and motor-evoked potential (MEP) latencies. The use of navigation in TMS and ensuring correct PNS electrode placement with F-response recording enhances the precision of the method. RESULTS: Our protocol induced 186±17% (mean±STE) MEP amplitude facilitation in healthy subjects, being effective in all subjects and nerves tested. COMPARISON WITH EXISTING METHOD: We report for the first time the individual estimation of ISIs in spinal PAS for lower limbs. CONCLUSIONS: Estimation of ISI on the basis of F and MEP latencies is sufficient to effectively enhance corticospinal transmission by lower limb spinal PAS in healthy subjects.

Alterations in spontaneous brain oscillations during stroke recovery.

Amplitude or frequency alterations of spontaneous brain oscillations may reveal pathological phenomena in the brain or predict recovery from brain lesions, but the temporal evolution and the functional significance of these changes is not well known. We performed follow-up recordings of spontaneous brain oscillations with whole-head MEG in 16 patients with first-ever stroke in the middle cerebral artery territory, affecting upper limb motor function, 1-7 days (T0), 1 month (T1), and 3 months (T2) after stroke, with concomitant clinical examination. Clinical test results improved significantly from T0 to T1 or T2. During recovery (at T1 and T2), the strength of temporo-parietal ≈ 10-Hz oscillations in the affected hemisphere (AH) was increased as compared with the unaffected hemisphere. Abnormal low-frequency magnetic activity (ALFMA) at ≈ 1 Hz in the AH was detected in the perilesional cortex in seven patients at T0. In four of these, ALFMA persisted at T2. In patients with ALFMA, the lesion size was significantly larger than in the rest of the patients, and worse clinical outcome was observed in patients with persisting ALFMA. Our results indicate that temporo-parietal ≈ 10-Hz oscillations are enhanced in the AH during recovery from stroke. Moreover, stroke causes ALFMA, which seems to persist in patients with worse clinical outcome.

Effect of afferent input on motor cortex excitability during stroke recovery.

OBJECTIVE: Afferent input is proposed to mediate its effect on motor functions by modulating the excitability of the motor cortex. We aimed to clarify - in a longitudinal study - how afferent input affects motor cortex excitability after stroke and how it is associated with recovery of hand function. METHODS: The motor cortex excitability was studied by measuring the reactivity of the motor cortex beta rhythm to somatosensory stimulation. We recorded the amplitude of the suppression and subsequent rebound of the beta oscillations during tactile finger stimulation with MEG in 23 first-ever stroke patients within one week and at 1 and 3 months after stroke, with concomitant evaluation of hand function. RESULTS: The strength of the beta rhythm rebound, suggested to reflect decreased motor cortex excitability, was weak in the affected hemisphere after stroke and it was subsequently increased during recovery. The rebound strength correlated with hand function tests in all recordings. CONCLUSION: Motor cortex excitability is modulated by afferent input after stroke. The motor cortex excitability is increased in the AH acutely after stroke and decreases in parallel with recovery of hand function. SIGNIFICANCE: The results implicate the importance of parallel recovery of both sensory and motor systems in functional recovery after stroke.

Pre- and post-operative diffusion tensor imaging of the median nerve in carpal tunnel syndrome.

OBJECTIVES: To use pre- and post-operative diffusion tensor imaging (DTI) to monitor median nerve integrity in patients suffering from carpal tunnel syndrome (CTS). METHODS: Diffusivity and anisotropy images along the median nerve were compared among 12 patients, 12 age-matched and 12 young control subjects and correlated with electrophysiological neurography results. Slice-wise DTI parameter values were calculated to focus on local changes. RESULTS: Results of pre-operative patients and age-matched control subjects differed only in the distal nerve. Moreover, pre-operative patients differed significantly from young controls and post-operative patients. The main abnormalities were increased diffusivity and decreased anisotropy in the carpal tunnel and distal median nerve. Post-operative clinical improvement was reflected in diffusivity, but not in anisotropy. Slice-wise analysis showed high pre-operative diffusivity at the distal nerve. All groups had relatively large inter-subject variation in both diffusivity and anisotropy. CONCLUSIONS: DTI can provide information complementary to clinical examination, electrophysiological recordings and anatomical MRI of diseases and injuries of peripheral nerves. However, similar age-related changes in diffusivity and anisotropy may weaken DTI specificity. Slice-wise analysis is necessary for detection of local changes in nerve integrity. KEY POINTS: • Diffusion tensor magnetic resonance imaging provides information complementary to conventional diagnostic methods. • Age caused similar changes to diffusivity and anisotropy as carpal tunnel syndrome. • Post-operative clinical improvement was reflected in diffusivity, but not in anisotropy. • Inter-subject variation in diffusivity and anisotropy was considerable.

Activation in parietal operculum parallels motor recovery in stroke.

Motor recovery after stroke requires continuous interaction of motor and somatosensory systems. Integration of somatosensory feedback with motor programs is needed for the automatic adjustment of the speed, range, and strength of the movement. We recorded somatosensory evoked fields (SEFs) to tactile finger stimulation with whole-scalp magnetoencephalography in 23 acute stroke patients at 1 week, 1 month, and 3 months after stroke to investigate how deficits in the somatosensory cortical network affect motor recovery. SEFs were generated in the contralateral primary somatosensory cortex (SI) and in the bilateral parietal opercula (PO) in controls and patients. In the patients, SI amplitude or latency did not correlate with any of the functional outcome measures used. In contrast, the contralateral PO (cPO) amplitude to the affected hand stimuli correlated significantly with hand function in the acute phase and during recovery; the weaker the PO activation, the clumsier the hand was. At 1 and 3 months, enhancement of the cPO activation paralleled the improvement of the hand function. Whole-scalp magnetoencephalography measurements revealed that dysfunction of somatosensory cortical areas distant from the ischemic lesion may affect the motor recovery. Activation strength of the PO paralleled motor recovery after stroke, suggesting that the PO area is an important hub in mediating modulatory afferent input to motor cortex.

Reorganization of the primary somatosensory cortex during stroke recovery.

OBJECTIVE: Animal and human studies have indicated that stroke induces reorganization of the motor and somatosensory cortices. We aimed to clarify how changes in the primary somatosensory (SI) cortex correlate with stroke recovery. METHODS: We recorded somatosensory evoked fields (SEFs) with magnetoencephalography from 15 patients with stroke affecting upper extremity motor function. The size of the hand representation in the SI cortex was calculated from the Euclidean distance between the sources of SEFs to thumb and little finger tactile stimulation. The measurements were made at 1-7 days (T0), at 1 (T1), and at 3 months (T2) after stroke, with concomitant evaluation of hand function. RESULTS: The affected hand function was improved at T1 and T2 compared with T0 (p<0.01). At T1, the SI hand representation in the affected hemisphere was enlarged compared with T0 or T2 (12.6±0.8 at T1 vs. 9.6±0.8 mm at T0 and 10.2±0.8 at T2, p<0.05). In patients with subcortical infarction, the increase in cortical representation at T1 correlated strongly with impairment of hand function (r=0.8, p<0.01). CONCLUSION: Reorganization of the SI cortex provokes a transient enlargement of the hand representation that normalizes as hand functions are regained. SIGNIFICANCE: The temporal evolution of plastic changes during stroke recovery might be useful in evaluating motor recovery.

Motor cortex dysfunction in complex regional pain syndrome.

OBJECTIVE: Most patients with complex regional pain syndrome (CRPS) exhibit debilitating motor symptoms. The effect of continuous pain on motor system in CRPS, however, is not well known. We searched for signs of motor cortex dysfunction in chronic CRPS type 1 patients with motor impairment. METHODS: We recorded rhythmic brain activity with magnetoencephalography (MEG) during noxious thulium-laser stimulation of both hands in eight CRPS patients and eight control subjects. We measured excitability of the motor cortex by monitoring the reactivity of the approximately 20-Hz motor cortex rhythm to laser stimuli. The reactivity was defined as a sum of the stimulus-induced suppression and the subsequent rebound of the approximately 20-Hz rhythm. RESULTS: In CRPS, the reactivity of the approximately 20-Hz rhythm in the hemisphere contralateral to the painful hand was significantly weaker than in control subjects. The reactivity correlated with the mean level of the spontaneous pain (r=-0.64, P=0.04). Suppression of the approximately 20-Hz rhythm correlated with the grip strength in the painful hand (r=0.66, P=0.04). CONCLUSION: Continuous pain in CRPS is associated with attenuated motor cortex reactivity. SIGNIFICANCE: Abnormal motor cortex reactivity may be linked with motor dysfunction of the affected hand in CRPS.