Ipsilateral motor pathway confirmed by combined brain mapping of a patient with hemiparetic stroke: a case report

This study investigated the motor control pathway using both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in a patient with left hemiparesis with an infarction on the posterior limb of the right internal capsule. fMRI was performed using the blood oxygen level-dependent technique at 1.5 T with a standard head coil. The motor activation task consisted of hand grasp-release movements in 1-Hz cycles. TMS was performed using a butterfly coil; the intersection of the wings (center of the coil) was applied tangentially to the scalp 1.0 cm apart. Stimulation was performed at 100% of maximal output. Motor evoked potentials (MEPs) from both abductor pollicis brevis (APB) muscles were obtained simultaneously. fMRI showed that the unaffected (left) primary sensorimotor cortex (SM1) was activated by movements of the unaffected (right) hand. Conversely, the bilateral SM1 were activated by movements of the affected (left) hand. Brain mapping using TMS showed that ipsilateral MEPs were obtained at the affected (left) APB muscle when the unaffected (left) motor cortex was stimulated. We concluded that the ipsilateral motor pathway from the unaffected motor cortex to the affected hand was present in this patient.     

Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.     

Ipsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions

Distal, unilateral hand movements can be associated with activation of both sensorimotor cortices on functional MRI. The neurophysiological significance of the ipsilateral activation remains unclear. We examined 10 healthy right-handed subjects with and without activation of the ipsilateral sensorimotor area during unilateral index-finger movements, to examine ipsilateral, uncrossed-descending pathways and interhemispheric interaction between bilateral motor areas, using transcranial magnetic stimulation (TMS). No subject showed ipsilateral activation during right hand movement. Five subjects showed ipsilateral sensorimotor cortical activation during left hand movement (IpsiLM1). In these subjects, paired-pulse TMS revealed a significant interhemispheric inhibition of the left motor cortex by the right hemisphere that was not present in the 5 subjects without IpsiLM1. Neither ipsilateral MEPs nor ipsilateral silent periods were evoked by TMS in any subjects. Our observation suggests that IpsiLM1 is not associated with the presence of ipsilateral uncrossed-descending projections. Instead, IpsiLM1 may reveal an enhanced interhemispheric inhibition from the right hemisphere upon the left to suppress superfluous, excessive activation.     

Comparison of navigated and non-navigated transcranial magnetic stimulation for motor cortex mapping, motor threshold and motor evoked potentials

Transcranial magnetic stimulation (TMS) can be used for non-invasive assessment of cortical physiology and descending motor pathways. However, the focus/exact site of cortical activation is considerably widespread in traditional TMS. When combined with MRI-based navigation, it allows specific anatomical areas of the cortex to be stimulated. The peripheral muscle responses to TMS are commonly measured as motor evoked potentials (MEPs). We compared the accuracy of cortical mapping, as well as the congruity of the motor thresholds (MT) and MEPs between navigated and non-navigated TMS procedures. Eight volunteers were studied in two sessions. In each session both hemispheres were stimulated with and without navigation. Non-navigated TMS: Both hemispheres were mapped without navigation to find the representation area of the thenar muscles based on induced MEP amplitudes. MT was then determined at the optimum coil location. Navigated TMS: Individual MR-images were used for the on-line navigation procedure. The cortical representation area of the thenar musculature was mapped at the "hand knob". The optimum stimulus target was used for MT determination. The order of these two procedures was randomized. Following the MT determination, MEPs were recorded from 20 consecutive stimuli. The MTs were similar from session-to-session with no inter-hemispheric differences, and with and without navigation. The stimulus location was more spatially discrete in navigated TMS producing more stable MEPs with significantly higher amplitudes and shorter latencies. In summary, MEPs exhibit significant differences depending on whether navigation is used. However, the MTs are not significantly dependent on the discrete stimulation site.     

A stereotactic method for image-guided transcranial magnetic stimulation validated with fMRI and motor-evoked potentials

Transcranial Magnetic Stimulation (TMS) delivers short magnetic pulses that penetrate the skull unattenuated, disrupting neural processing in a noninvasive, reversible way. To disrupt specific neural processes, coil placement over the proper site is critical. Therefore, a neural navigator (NeNa) was developed. NeNa is a frameless stereotactic device using structural and functional magnetic resonance imaging (fMRI) data to guide TMS coil placement. To coregister the participant's head to his MRI, 3D cursors are moved to anatomical landmarks on a skin rendering of the participants MRI on a screen, and measured at the head with a position measurement device. A method is proposed to calculate a rigid body transformation that can coregister both sets of coordinates under realistic noise conditions. After coregistration, NeNa visualizes in real time where the device is located with respect to the head, brain structures, and activated areas, enabling precise placement of the TMS coil over a predefined target region. NeNa was validated by stimulating 5 x 5 positions around the 'motor hotspot' (thumb movement area), which was marked on the scalp guided by individual fMRI data, while recording motor-evoked potentials (MEPs) from the abductor pollicis brevis (APB). The distance between the center of gravity (CoG) of MEP responses and the location marked on the scalp overlying maximum fMRI activation was on average less then 5 mm. The present results demonstrate that NeNa is a reliable method for image-guided TMS coil placement.     

Examining cortical dynamics and connectivity with simultaneous single-pulse transcranial magnetic stimulation and fast optical imaging

Transcranial magnetic stimulation (TMS) is a widely used experimental and clinical technique that directly induces activity in human cortex using magnetic fields. However, the neural mechanisms of TMS-induced activity are not well understood. Here, we introduce a novel method of imaging TMS-evoked activity using a non-invasive fast optical imaging tool, the event-related optical signal (EROS). EROS measures changes in the scattering of near-infrared light that occur synchronously with electrical activity in cortical tissue. EROS has good temporal and spatial resolution, allowing the dynamics and spatial spread of a TMS pulse to be measured. We used EROS to monitor activity induced in primary motor cortex (M1) by a TMS pulse. Left- and right-hand representations were mapped using standard TMS procedures. Optical sources and detectors mounted on thin rubber patches were then centered on M1 hand representations. EROS was recorded bilaterally from motor cortex while unilateral TMS was simultaneously delivered. Robust ipsilateral EROS activations were apparent within 16 ms of a pulse for TMS delivered to both left and right hemispheres. Clear motor evoked potentials (MEPs) were also elicited by these TMS pulses. Movement artifacts could be excluded as a source of EROS, as no activation was present on short-distance optical channels. For left hemisphere TMS subsequent (40 ms) contralateral activity was also present, presumably due to trans-synaptic propagation of TMS-evoked activity. Results demonstrate that concurrent TMS/EROS is a viable and potentially powerful method for studying TMS-induced activity in the human brain. With further development, this technique may be applied more broadly in the study of the dynamics of causal cortico-cortical connectivity.     

Effects of treadmill exercise on transcranial magnetic stimulation-induced excitability to quadriceps after stroke

OBJECTIVE: To determine characteristics of transcranial magnetic stimulation (TMS)-induced measures of central motor excitability to the paretic and nonparetic quadriceps muscles of chronic hemiparetic stroke patients in the context of a short-term, submaximal bout treadmill exercise. DESIGN: Cross-sectional. SETTING: Motor control and gait biomechanics laboratory. PARTICIPANTS: Convenience sample of 11 patients including cohorts of treadmill untrained (n=8) and trained (n=3) stroke patients with chronic hemiparetic gait. INTERVENTION: Short-term submaximal treadmill exercise. MAIN OUTCOME MEASURES: Thresholds, amplitudes and latencies of TMS-induced motor evoked potentials at vastus medialis in paretic and nonparetic lower extremities. RESULTS: Baseline characteristics of the motor evoked potentials (MEPs) show significantly higher motor thresholds, longer latencies, and reduced amplitudes on the paretic side. In cross-sectional comparisons a group of treadmill-trained patients had greater paretic MEP amplitude changes after treadmill exercise versus paretic MEP responses from a group of untrained patients. CONCLUSIONS: These results indicate that treadmill training for 3 months or more may alter responsiveness of the lower-extremity central motor pathways to a short-term treadmill stimulus.     

Modulation of excitability in the cerebral cortex projecting to upper extremity muscles by rotational positioning of the forearm

The forearm rotation changes sensory inputs to the central nervous system, thereby providing orientation of the hand for grasping an object. Electrical activities of the muscles, induced by transcranial magnetic stimulation to the brain, i.e., motor evoked potentials (MEPs), are used for estimation of the excitability of motor neurons in the brain and spinal cord. It is well known that rotational positioning of the forearm influences MEPs of forearm muscles through modulation of excitability in the central nervous system. In the present study, we investigated whether such a posture-dependent change of MEPs could be found in upper arm and intrinsic hand muscles at three different rotational forearm positions: the most internal (pronation), neutral, and most external (supination) positions of rotation. MEPs were simultaneously recorded from the four muscles, biceps brachii (BB), triceps brachii (TB), abductor digiti minimi (ADM), and abductor pollicis brevis (AbPB). MEP amplitudes and latencies in BB, TB and ADM were significantly larger and shorter, respectively, in supination compared to the values in other positions. By contrast, MEP of AbPB in supination was lower in amplitude and longer in latency. Importantly, muscle lengths of TB, ADM and AbPB are constant in any rotational forearm positions, excluding the possibility of the muscle-length dependent change of spinal reflex. Therefore, these results might be attributable to the posture-dependent modulation of the motor cortex activity for the upper limb. The motor cortex probably changes the control strategy for the upper limb muscles in accordance with the sensory input from the forearm.     

Theta-burst stimulation: remote physiological and local behavioral after-effects

Theta-burst stimulation (TBS), a novel repetitive transcranial magnetic stimulation (TMS) protocol, is capable of suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after the end of a conditioning train over the motor cortex. It remains unknown whether TBS leads to effects on motor cortical excitability when applied to contralateral brain sites distant but connected to motor cortex and whether TBS triggers measurable changes in force control. Subjects received bursts (50 Hz) of three subthreshold magnetic stimuli repeated at 5 Hz for 20 s (TBS-300) or 40 s (TBS-600) over the hand area of the left motor cortex (M1(LEFT)). With TBS-300, conditioning of right motor cortex (M1(RIGHT)), right dorsal premotor cortex (PMd(RIGHT)), and a mid-occipital (MO) region also were tested. Corticospinal excitability was probed by evoking MEPs in abductor pollicis brevis (APB) muscle by single suprathreshold stimuli over M1(LEFT) or M1(RIGHT) before and after TBS. Force level control was assessed in an isometric right thumb abduction task. With TBS-600, the time course of physiological and behavioral changes was monitored. TBS over either of the motor cortices reduced the amplitude of MEP in the contralateral APB and increased it in the ipsilateral APB. In contrast, conditioning TBS over PMd(RIGHT) or MO did not modify MEP size. Post-TBS right thumb force level control was impaired, with contralateral M1(LEFT) stimulation only, for a duration of at least 5 min. TBS may induce remote physiological effects and reveals local functional properties of the underlying brain region.     

针刺曲池、外关穴调节长时程增强样脑可塑性的研究

目的:观察单侧针刺曲池穴、外关穴的不同针刺状态对健康受试者双侧运动皮层(M1)长时程增强(LTP)样脑可塑性的影响。方法:纳入18名健康受试者,取右侧曲池、外关穴,给予常规普通针刺,进针后行针,得气为度。于针刺前15 min、进针后30 min及拔针后20 min分别使用经颅磁刺激运动诱发电位(TMSMEP)检测皮层兴奋性,观察单侧针刺对成对关联刺激(PAS)诱导LTP脑可塑性的影响。操作方法:①TMSMEP的诱导:进行TMS刺激点定位,找到以最小的刺激强度产生最大MEP波幅的位置,即为FDI皮层运动点;并使用TMS外固定架固定线圈、激光定位仪监测。②检测静息运动诱发电位阈值(rMT):基于FDI对应的皮层运动点,寻找给予10次TMS刺激能够产生至少5个MEP波幅≥50μV的刺激强度,记录为rMT。③短潜伏期尺神经体感诱发电位的测定:刺激电极置于FDI肌腹,阴极在近端,刺激电流5~10 mA,刺激强度为食指轻微抽动为宜。④PAS-LTP脑可塑性的诱导:使用电刺激加磁刺激进行诱导,共200对刺激。每位受试者需进行8次检测,每次约80 min。2次检测需间隔1周,以避免针刺后效应影响试验结果。结果:①与针刺前比较,留针时针刺对侧M1区MEP波幅比降低,针刺同侧M1区MEP波幅比升高;拔针后,针刺双侧M1区MEP波幅比均升高;差异均有统计学意义(P<0.01)。②PAS诱导后,留针时针刺同侧M1区MEP波幅升高;起针后,针刺双侧M1区MEP波幅均升高;差异均有统计学意义(P<0.01)。结论:单侧单次针刺曲池、外关穴不同针刺状态(留针、拔针后)对双侧LTP脑可塑性的影响不同,可以通过调节皮层兴奋性特异性改变双侧皮层的可塑性。     

Transcranial magnetic stimulation for detection of preclinical cervical spondylotic myelopathy.

Twenty-three patients, mean age 50.4 years, with cervical radiculopathy at C7 or more rostrally, were studied with electromyography, CT scans (in 16 cases) and transcranial magnetic stimulation. None had overt evidence of myelopathy. Motor evoked potentials (MEPs) were recorded from the hand muscles (C8/T1), and latency, amplitude, and the MEP/CMAP ratio and central motor delay between the hand motor cortex and the lower cervical spine were measured. One or more of these were abnormal in 15 of 23 cases (65%). The most common abnormality was a reduced MEP/CMAP ratio. The findings indicate that physiologic dysfunction of the spinal cord, caudal to a radiculopathy, frequently accompanies a radiculopathy and may antedate overt cervical spondylotic myelopathy. This may be valuable in directing more timely surgical intervention.     

Two different reorganization patterns after rehabilitative therapy: an exploratory study with fMRI and TMS

We used two complementary methods to investigate cortical reorganization in chronic stroke patients during treatment with a defined motor rehabilitation program. BOLD ("blood oxygenation level dependent") sensitive functional magnetic resonance imaging (fMRI) and intracortical inhibition (ICI) and facilitation (ICF) measured with transcranial magnetic stimulation (TMS) via paired pulse stimulation were used to investigate cortical reorganization before and after "constraint-induced movement therapy" (CI). The motor hand function improved in all subjects after CI. BOLD signal intensity changes within affected primary sensorimotor cortex (SMC) before and after CI showed a close correlation with ICI (r = 0.93) and ICF (r = 0.76) difference before and after therapy. Difference in number of voxels and ICI difference before and after CI also showed a close correlation (r = 0.92) in the affected SMC over the time period of training. A single subject analysis revealed that patients with intact hand area of M1 ("the hand knob") and its descending motor fibers (these patients revealed normal motor evoked potentials [MEP] from the affected hand) showed decreasing ipsilesional SMC activation which was paralleled by an increase in intracortical excitability. This pattern putatively reflects increasing synaptic efficiency. When M1 or its descending pyramidal tract was lesioned (MEP from the affected hand was pathologic) ipsilesional SMC activation increased, accompanied by decreased intracortical excitability. We suggest that an increase in synaptic efficiency is not possible here, which leads to reorganization with extension, shift and recruitment of additional cortical areas of the sensorimotor network. The inverse dynamic process between both complementary methods (activation in fMRI and intracortical excitability determined by TMS) over the time period of CI illustrates the value of combining methods for understanding brain reorganization.     

Transcranial Magnetic Stimulation Can Be Used to Test Connections to Primary Motor Areas from Frontal and Medial Cortex in Humans

Surface EMG responses (MEPs) were recorded from the relaxed first dorsal interosseous (FDI) of 16 normal subjects following transcranial magnetic stimulation (TMS) over the hand area of the primary motor cortex. These test responses were conditioned by a subthreshold stimulus applied 2-15 ms beforehand over a range of anterior or medial sites. Stimuli applied 3-5 cm anterior to the hand motor area (site A) or 6 cm anterior to the vertex on the nasion-inion line (site B) inhibited the test responses at short latency. The largest effect was seen when the interstimulus interval was 6 ms and the intensity of the conditioning stimulus was equal to 0.9x active motor threshold (AMT) at the hand area. Increasing the intensity to 1.2x AMT produced facilitation. Suppression of surface EMG responses was mirrored in the behavior of single motor units. Conditioning stimuli had no effect on responses evoked in the active FDI muscle by transcranial electric stimulation of motor cortex nor on forearm flexor H reflexes even though MEPs in the same muscle were suppressed at appropriate interstimulus intervals. We conclude that low-intensity TMS over presumed premotor areas of frontal cortex can engage corticocortical connections to the primary motor hand area.     

Suppression of premotor cortex disrupts motor coding of peripersonal space

Peripersonal space (PPS) representation depends on the activity of a fronto-parietal network including the premotor cortex (PMc) and the posterior parietal cortex (PPc). PPS representation has a direct effect on the motor system: a stimulus activating the PPS around the hand modulates the excitability of hand representation in the primary motor cortex. However, to date, direct information about the involvement of the PMc-PPc network in the motor mapping of sensory events occurring within PPS is lacking. To address this issue, we used a 'perturb-and-measure' paradigm based on the combination of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) techniques. Cathodal tDCS was applied to transiently suppress neural activity in PMc, PPc and primary visual cortex (V1; serving as an active control site); single-pulse TMS was used to induce motor-evoked potentials (MEPs) from hand muscles and so to measure the excitability of the hand motor representation. MEPs were compared when a sound was presented either near the hand or at a distance. In experimental sessions performed after sham-tDCS and after tDCS over the control area V1, we found a spatially dependent modulation of the hand motor representation: sounds presented near the hand induced an inhibitory motor response as compared to sounds presented far apart. Critically, this effect was selectively abolished after tDCS suppression of neural activity in PMc, but not when perturbing the activity of PPc. These findings suggest that PMc has a critical role in mapping sensory representations of space onto the motor system.     

不同侧小脑半球Theta爆发式经颅磁刺激对健康受试者吞咽调节效应的影响

目的观察间歇性Theta爆发式经颅磁刺激(iTBS)对健康受试者大脑吞咽运动皮质和小脑吞咽运动区兴奋性的影响, 并探讨小脑iTBS调节吞咽功能的机制。方法采用随机数字表法将44例右利手健康受试者分为优势侧小脑组(15例)、非优势侧小脑组(15例)、对照组(14例)。优势侧小脑组给予优势侧小脑iTBS干预和非优势侧小脑假刺激, 非优势侧小脑组给予优势侧小脑假刺激和非优势侧小脑iTBS干预, 对照组给予双侧小脑假刺激。iTBS干预前后, 分别对受试者双侧大脑和双侧小脑的舌骨上肌群代表区进行单脉冲经颅磁刺激(TMS)测定, 观察受试者运动诱发电位(MEP)波幅和潜伏期的变化。结果与组内干预前比较, 非优势侧小脑组干预后双侧大脑吞咽皮质和刺激同侧小脑的MEP波幅升高(P<0.05);优势侧小脑组干预后仅刺激同侧小脑的MEP波幅升高(P<0.05)。在MEP波幅与基线相比的百分比变化方面, 与对照组干预后同指标比较, 非优势侧小脑组刺激双侧大脑皮质和刺激同侧小脑的数值较高(P<0.05);与非优势侧小脑组干预后同指标比较, 优势侧小脑组刺激双侧大脑皮质的数值较低(P<0....     

A novel dual-site transcranial magnetic stimulation paradigm to probe fast facilitatory inputs from ipsilateral dorsal premotor cortex to primary motor cortex

The dorsal premotor cortex (PMd) plays an import role in action control, sensorimotor integration and motor recovery. Animal studies and human data have demonstrated direct connections between ipsilateral PMd and primary motor cortex hand area (M1(HAND)). In this study we adopted a multimodal approach combining highly focal dual-site TMS (dsTMS) and diffusion tensor imaging (DTI) to probe ipsilateral effective and structural connectivity between PMd and M1(HAND) in humans. A suprathreshold test stimulus (TS) was applied to left M1(HAND) producing a motor evoked potential (MEP) and a subsequent conditioning stimulus (CS) to ipsilateral rostromedial PMd at short latencies ranging from of 0.8 to 2.0 ms. At an interstimulus interval of 1.2 ms, dsTMS of the left M1(HAND) and PMd facilitated MEP amplitudes relative to unconditioned TMS of M1(HAND). This PMd to M1(HAND) facilitation was absent during voluntary contraction of the target muscle. During a two-choice reaction time task, PMd-M1(HAND) facilitation was only observed when dsTMS was given 125 ms after presentation of the cue and subjects responded with their right hand, but not for left hand responses. Our results reveal a short-latency PMd to M1(HAND) connection which modulates excitability of ipsilateral M1(HAND) in a task and effector specific manner. DTI revealed that individual increases in PMd to M1(HAND) facilitation were correlated with fractional anisotropy and axial diffusivity in the juxtacortical white matter underlying the caudal portion of the left superior frontal gyrus. This finding shows that the functional strength of this connection from medial PMd to M1(HAND) has a microstructural correlate in the underlying subcortical white matter. This novel dsTMS paradigm can be used to non-invasively probe effective PMd to M1(HAND) connectivity in healthy individuals and patients with impaired hand function.     

Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes

This article reviews methods that have been developed as part of a clinical initiative on improving outcome measures for motor function assessment in subjects with spinal cord injury (SCI). Physiological motor outcome measures originally developed for limbs-transcranial magnetic stimulation (TMS) of the motor cortex to elicit motor-evoked potentials (MEPs) and mechanical stimulation to elicit spinal reflexes-have been extended to muscles of the trunk. The impetus for this development is the lack of a motor component in the American Spinal Injury Association clinical assessment for the thoracic myotomes. The application of TMS to the assessment of limb muscles is reviewed, followed by consideration of its application to the assessment of paravertebral and intercostal muscles. Spinal reflex testing of paravertebral muscles is also described. The principal markers for the thoracic SCI motor level that have emerged from this clinical initiative are (1) the threshold of MEPs in paravertebral muscles in response to TMS of the motor cortex, (2) the facilitation pattern and latency of MEPs in intercostal muscles during voluntary expiratory effort, and (3) the absence of long-latency reflex responses and the exaggeration of short-latency reflex responses in paravertebral muscles.     

Cerebro-muscular and cerebro-cerebral coherence in patients with pre- and perinatally acquired unilateral brain lesions

The cerebral networks involved in motor control were analyzed in four young hemi-paretic patients (21-25 years) with pre- and perinatally acquired brain lesions (3 with left periventricular brain lesions, 1 with left schizencephaly) by means of MEG source coherence analysis. Previous TMS and fMRI studies on the same patients had investigated their residual ability to move the paretic hand by means of a reorganized primary motor cortex (M1) representation in the contralesional hemisphere. The purpose of this study is to identify the effects of such a cerebral reorganization and the related dynamic aspects which allow the patients to move the paretic arm. Patients underwent a pinch grip task (1-N isometric contraction) using their paretic and non-paretic hands in alternation. MEG signals were recorded using a whole-head 151-channel magnetoencephalograph. EMG was simultaneously recorded as a reference for coherence calculations. 3D coherence mapping was performed in the beta frequency range (14-30 Hz). This approach confirmed the relocation of motor functions from the lesioned (left) to the contralesional (right) hemisphere. In case of left, non-paretic pinch grip, coherent activity originated from contralateral (right) M1 exclusively. In the case of right (paretic) grip, coherent activity in ipsilateral M1 as well as significant coherence of ipsilateral cerebellum with both muscle activity and M1 itself was detected in 3 out of 4 subjects. As expected, the patient with no cerebellar involvement during paretic hand contraction showed the worst motor performance in the grip task. Coupling direction analysis demonstrated that throughout pinch grip the coupling direction goes from M1 to cerebellum. The present study verified the assumption that the intact hemisphere takes over motor control from the paretic (ipsilateral) hand in the presence of early unilateral brain lesion. Moreover, the role of cerebellum in motor deficit compensation and its close interaction with ipsilateral primary motor cortex was studied in detail.     

Integrated technology for evaluation of brain function and neural plasticity

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.     

Prefrontal transcranial magnetic stimulation produces intensity-dependent EEG responses in humans

The reactivity of the prefrontal cortex (PFC) was studied by measuring electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS) with different stimulus intensities. Focal TMS at intensities of 60%, 80%, 100%, and 120% of the motor threshold was delivered to the left middle frontal gyrus identified individually from magnetic resonance images (MRI) in seven healthy subjects. EEG was simultaneously recorded with 60 scalp electrodes. Stimulation evoked clear responses at all intensities. Left prefrontal TMS evoked an averaged EEG response consisting of five deflections at 27 +/- 3 ms (peak I), 39 +/- 3 ms (II), 52 +/- 7 ms (III), 105 +/- 14 ms (IV), and 193 +/- 15 ms (V) at the Fz/FCz electrodes. The slope of the almost linear dependence of the overall response on stimulus intensity varied with latency. Potential distributions were relatively similar for the four intensities, suggesting that the same cortical structures may be activated. Intensity dependence function to TMS may be an indicator of cortical activation in humans.