Regional cerebral blood flow correlates of the severity of writer's cramp symptoms

Writer's cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O to find out in which brain areas activity correlates with the severity of writer's cramp symptoms. METHODS: We studied 10 patients with writer's cramp and 10 age- and gender-matched control subjects. There were seven conditions, each repeated twice: rest, writing, tapping with index finger for 2, 3, 4, and 5 min. For each scan, we obtained EMG recordings from the flexor digitorum superficialis (FDS), extensor indicis proprius (EIP) muscles, and a subjective score of severity of dystonia. Scans were realigned, normalized, smoothed, and analyzed using SPM99. Analysis included both intra- and intergroup comparisons and a correlation analysis where we used EMG recordings and subjective dystonia score as covariates. RESULTS: Random effect analysis of the writing task showed overactivity of the primary sensory cortex and no significant underactivity. Correlation analysis of dystonia patients showed activation of SI when we used the subjective dystonia score as a covariate, and activation of both the SI and primary motor cortex when the normalized EMG score of FDS was used. CONCLUSION: While some overactivity of MI is not surprising, overactivity of SI is more dramatic and suggests a primary deficit in processing sensory feedback. Writer's cramp may arise in part as a dysfunction of sensory circuits, which causes defective sensorimotor integration resulting in co-contractions of muscles and overflow phenomena.     

Electroencephalographic spectral power in writer's cramp patients: evidence for motor cortex malfunctioning during the cramp

We investigated cortical activation as reflected in task-related spectral power (TRPow) changes in 8 writer's cramp patients during writing on a digital board and during isometric contraction and compared them to those of 8 age-matched healthy subjects. Scalp EEG was recorded over the contralateral primary sensorimotor area (SM1(c)), and from the ipsilateral sensorimotor area (SM1(i)). The electromyogram (EMG) was recorded from the Extensor Digitorum Communis (Extensor), Flexor Digitorum Superficialis (Flexor), and First Dorsal Interosseous (FDI) muscles. We analyzed (1) handwriting performance, (2) changes in the TRPow confined to alpha and beta band, and (3) the EMG spectral power during both tasks, writing and isometric contraction. During writing, all patients developed writer's cramp. The handwriting in writer's cramp patients was associated with significantly less reduction of the beta-range TRPow and lower frequency of the TRPow reduction compared to controls. No significant differences between patients and controls for the alpha band TRPow reduction during handwriting were observed. During writing, the patients showed higher EMG spectral power than the controls but this difference was at the border of significance. The present results indicate disorder in the motor execution system, in writer's cramp patients, associated with impaired functional beta-network state of the contra- and ipsilateral sensorimotor cortices, most probably due to inadequate modulation of the intracortical inhibition associated with writing.     

Hand posture modulates cortical finger representation in SII

Somatosensory magnetic fields evoked by electrical stimuli of the thumb or the index finger were recorded using a whole head magnetoencephalography (MEG) system in 10 subjects performing different finger postures, open hand posture and close hand posture for picking up a small object. The mean Euclidean distances between the ECD (equivalent current dipole) locations for the thumb and index finger in the secondary somatosensory cortex (SII) across the subjects were 8.5 +/- 2.1 mm in the close hand posture and 11.2 +/- 2.6 mm in the open hand posture. The distance was significantly shorter in the close hand posture (paired t test, P = 0.002, n = 8). However, the distances of the P38m and P60m components in the primary somatosensory cortex (SI) were not significantly different between the two hand postures (P38m: 13.4 +/- 5.6 mm in the open and 13.5 +/- 3.9 mm in the close; P60m: 12.4 +/- 2.6 mm in the open and 16.2 +/- 5.3 mm in the close). This shortening of the spatial distance between the cortical finger representations suggests a similarity in humans of the rapid changes in the dynamics of cortical circuits reported in animal studies. In addition, the overlap of the cortical finger representations, which might be suggested by the shortening of the distance between the ECDs in SII, is likely to play a role in information integration between sensory inputs from the thumb and index finger.     

Dynamic shifts in the organization of primary somatosensory cortex induced by bimanual spatial coupling of motor activity

Previous work has shown that training and learning can induce powerful changes in the homuncular organization of the primary somatosensory cortex (SI). Moreover, a number of studies suggest the existence of short-term adaptation of representational maps in SI. Recently, motor activity has been shown to induce rapid modulation of somatosensory cortical maps. It is hypothesized that there is a task-related influence of motor and premotor areas upon the organization of somatosensory cortex. In order to test this hypothesis, we studied the functional organization of somatosensory cortex by examining coupling effects in a bimanual movement task. Bimanual coupling is known to be related to an activation of the premotor cortex and the supplementary motor area. The functional organization of the somatosensory cortex for known bimanual coupling effects was compared to the organization of the somatosensory cortex during the same movements but with only a small effort in coupling. Topography of the functional organization of the somatosensory cortex was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We could show that the cortical representations of D1 and D5 moved further apart during the bimanual coupling task in comparison to the same task without coupling and rest. Our data suggest that somatosensory cortical maps undergo fast and dynamic modulation as a result of a task-related influence of motor or premotor areas.     

Altered central sensorimotor processing in patients with complex regional pain syndrome

Alterations in tactile sensitivity are common in patients with chronic pain. Recent brain imaging studies have indicated that brain areas activated by acute experimental pain partly overlap with areas processing innocuous tactile stimuli. However, the possible effect of chronic pain on central tactile processing has remained unclear. We have examined, both clinically and with whole-head magnetoencephalography, six patients suffering from complex regional pain syndrome (CRPS) of the upper limb. The cortical somatosensory responses were elicited by tactile stimuli applied to the fingertips and the reactivity of spontaneous brain oscillations was monitored as well. Tactile stimulation of the index finger elicited an initial activation at 65 ms in the contralateral SI cortex, followed by activation of the ipsi- and contralateral SII cortices at about 130 ms. The SI responses were 25-55% stronger to stimulation of the painful than the healthy side. The distance between SI representations of thumb and little finger was significantly shorter in the hemisphere contralateral than ipsilateral to the painful upper limb. In addition, reactivity of the 20-Hz motor cortex rhythm to tactile stimuli was altered in the CRPS patients, suggesting modified inhibition of the motor cortex. These results imply that chronic pain may alter central tactile and motor processing.     

Task-relevant modulation of primary somatosensory cortex suggests a prefrontal-cortical sensory gating system

Increasing evidence suggests that somatosensory information is modulated cortically for task-specific sensory inflow: Several studies report short-term adaptation of representational maps in primary somatosensory cortex (SI) due to attention or induced by task-related motor activity such as handwriting. Recently, it has been hypothesized that the frontal or prefrontal cortex may modulate SI. In order to test this hypothesis, we studied the functional organization of SI while subjects performed the Tower of Hanoi task. This task is known to be related to activation of frontal or prefrontal areas. The functional organization of SI while performing the Tower of Hanoi task was compared to the organization of SI during performing the same movements but without the Tower of Hanoi task and with rest. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digits (D5). Performing the Tower of Hanoi task was accompanied by plastic changes in SI as indicated by significant shifts in the cortical representations of D1 and D5: They moved further apart during the Tower of Hanoi task compared to the control task containing the same movements but without the cognitive characteristic. Thus, we conclude that SI maps undergo dynamic modulation depending on motor tasks with different cognitive demands. The results suggest that this short-term plasticity may be regulated by a prefrontal-cortical sensory gating system.     

fMRI reflects functional connectivity of human somatosensory cortex

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.     

书写痉挛责任肌群的认定及肉毒毒素治疗的疗效观察

目的　寻找引起患者书写痉挛 (writer scramp)并导致字迹抖动不清的主要责任肌群 ,并同时观察局部注射肉毒毒素 A (botulinumtoxin A ,BTX A)对书写痉挛病症的治疗效果及副反应发生情况。方法　通过对前臂肌群的选择性运动 ,判断各肌群对书写痉挛症状的影响 ,并初步认定责任肌群 ,然后用维库溴铵对初步确定的责任肌群进行选择性注射 ,以进一步确定引起书写痉挛的主要责任肌群 ,最后对已确定的主要责任肌群进行BTX A多点注射 ,观察其疗效及副反应发生情况。结果　本研究发现 ,当前臂旋转肌群运动时会加重书写痉挛症状 ,对该群肌肉注射维库溴铵后可消除痉挛症状。当对旋转肌群进行BTX A注射后 ,受试的 3例患者 (共 5侧患肢 )症状全部得到改善 ,无一例发生可察觉的握力减退及垂腕等副反应。结论　前臂旋转肌群是导致书写痉挛并致使字迹抖动不清的主要责任肌群 ,对其进行BTX A选择性多点注射可获得满意疗效 ,同时还可避免握力减退及垂腕等副反应的发生。     

Functional network of the basal ganglia and cerebellar motor loops in vivo: different activation patterns between self-initiated and externally triggered movements

The basal ganglia and cerebellar loops are known to participate differently in self-initiated (SI) and externally triggered (ET) movements. However, no previous neuroimaging studies have illustrated functional organization of these loops in vivo. Here, we aimed to functionally visualize these loops during motor execution using functional magnetic resonance imaging (fMRI) with structural equation modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while performing five different frequencies of sequential left finger movements using either SI or ET movements. Random effect analysis combined with a parametric approach revealed a significant positive linear dependence of cerebral activation upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During ET tasks, significant positive linear relationships were found in the right SMC, VPL, left CB and DN, whereas tendency for linear relationships was seen in the right PMv. SEM further showed significant interactions within the right basal ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant interactions within the entire right cerebral hemisphere-left cerebellar loop involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling approach enabled identification of different contributions of the motor loops of basal ganglia and cerebellum to SI and ET tasks during motor execution.     

Observation of action: grasping with the mind's hand

Engagement of the primary motor cortex (MI) during the observation of actions has been debated for a long time. In the present study, we used the quantitative 14C-deoxyglucose method in monkeys that either grasped 3-D objects or observed the same movements executed by humans. We found that the forelimb regions of the MI and the primary somatosensory (SI) cortex were significantly activated in both cases. Our study resolves a debate in the literature, providing strong evidence for use of MI representations during the observation of actions. It demonstrates that the observation of an action is represented in the primary motor and somatosensory cortices as is its execution. It indicates that in terms of neural correlates, recognizing a motor behavior is like executing the same behavior, requiring the involvement of a distributed system encompassing not only the premotor but also the primary motor cortex. We suggest that movements and their proprioceptive components are stored as motor and somatosensory representations in motor and somatosensory cortices, respectively, and that these representations are recalled during observation of an action.     

Enduring representational plasticity after somatosensory stimulation

Somatosensory stimulation (SS), leading to increases in motor cortical excitability, influences motor performance in patients with brain lesions like stroke. The mechanisms by which SS modulates motor function are incompletely understood. Here, we used functional magnetic resonance imaging (fMRI, blood-oxygenation-level-dependent (BOLD), and perfusion imagings simultaneously acquired in a 3 T magnet) to assess the effects of SS on thumb-movement-related activation in three regions of interest (ROI) in the motor network: primary motor cortex (M1), primary somatosensory cortex (S1), and dorsal premotor cortex (PMd) in healthy volunteers. Scans were obtained in different sessions before and after 2-h electrical stimulation applied to the median nerve at the wrist (MNS), to the skin overlying the shoulder deltoid muscle (DMS), and in the absence of stimulation (NOSTIM) in a counterbalanced design. We found that baseline perfusion intensity was comparable within and across sessions. MNS but not DMS nor NOSTIM led to an increase in signal intensity and number of voxels activated by performance of median nerve-innervated thumb movements in M1, S1, and PMd for up to 60 min. Task-related fMRI activation changes were most prominent in M1 followed by S1 and to a lesser extent in PMd. MNS elicited a displacement of the center of gravity for the thumb movement representation towards the other finger representations within S1. These results indicate that MNS leads to an expansion of the thumb representation towards other finger representations within S1, a form of plasticity that may underlie the influence of SS on motor cortical function, possibly supporting beneficial effects on motor control.     

"Gating" effects of simultaneous peripheral electrical stimulations on human secondary somatosensory cortex: a whole-head MEG study

The secondary somatosensory cortex (SII) is strongly involved in the processing of somatosensory tactile and nociceptive sensations. We investigated the effect on SII responses of simultaneous painful and nonpainful electrical stimulations delivered to the thumb and little finger. According to the "bimodal" (i.e., nociceptive, tactile) organization of SII, it was expected that simultaneous painful and nonpainful stimulations would lead to modality interference with a marked reduction ("gating") of somatosensory evoked fields (SEFs) generated in SII. Eight different stimulus conditions were studied. Two conditions were simultaneous "unimodal" (thumb and little finger nonpainful; thumb and little finger painful) and two conditions were simultaneous "bimodal" (thumb nonpainful and little finger painful; thumb painful and little finger nonpainful). As a reference, four conditions included stimulations at single sites (thumb nonpainful, little finger nonpainful, thumb painful, little finger painful). The gating phenomenon was defined as the percentage of difference between the intensities of SII activation after simultaneous compared to the sum of the separate stimulations. Results showed that simultaneous stimulations induced gating effects on SEFs generated by SII. No significant gating differences were observed after the two unimodal stimulations, suggesting a negligible effect of global energy on gating. Instead, the gating effects on bilateral SII activity were stronger after simultaneous bimodal when compared to unimodal stimulations. Our findings hint that there could be a greater level of integration/convergence of painful and nonpainful stimuli in SII with respect to SI. Future studies should explore if it could have an important role in exploring pain relief.     

Functional organization of primary somatosensory cortex depends on the focus of attention

We used magnetic source imaging in human subjects to reveal within-subject variations of the homuncular hand representation within the primary somatosensory cortex modulated by attention. In one condition subjects were trained to detect sequential leftward or rightward stimulus motion across the fingers of the left hand ("hand" condition) and in a different condition to detect stimulus motion at a specific finger on this hand ("finger" condition). Afferent input was controlled by applying exactly the same stimulus pattern to the digits in the two tasks. Segregation of the somatotopic hand representation (an increase in the distance between the representations of digits 2 and 5) was observed, commencing with the onset of practice, in the finger relative to the hand condition. Subsequent training in the hand and finger conditions with feedback for correctness did not modify segregation, indicating that segregation was a task effect and not a training effect. These findings indicate that the hand representation within the primary somatosensory cortex is not statically fixed but is dynamically modulated by top-down mechanisms to support task requirements. A greater capacity for modulation of the functional cortical organization was positively correlated with superior learning and task performance.     

Restoring balance in focal limb dystonia with botulinum toxin

Focal task-specific dystonia of the hand is rare in the general population, where it usually manifests as writer's cramp, but seems relatively common among musicians. The disability may be so severe as to prevent writing altogether or to end a professional musician's career. The cause is usually unknown but it is thought to be primarily a basal ganglia disorder with dysfunction of cortical-striatothalamic-cortical circuits. Abnormalities have been found in cortical movement preparation, intracortical inhibition, sensory and motor maps, and patterns of cortical activation during movement. Much evidence supports disordered processing of sensory information with disturbed sensorimotor integration. Underlying this may be maladaptive neural plasticity mechanisms. Treatment is difficult. Oral medications are generally ineffective and have troublesome side-effects. Intensive rehabilitation techniques based on neural plasticity theory show promise but are rarely available and are time-intensive. Botulinum toxin injections appear to be effective in writer's cramp and musician's dystonia, at least initially; long-term benefit is less common. Despite definite improvement, some patients abandon treatment because the gain is insufficient for meaningful function: this is particularly so for musicians. Much of the benefit from botulinum toxin injection comes from simply reducing muscle overactivity through muscle paralysis, restoring balance to motor control. However, some evidence suggests that botulinum toxin injections can produce transient improvement in some of the various cortical abnormalities described, probably through alteration of sensory input from the periphery, by direct and indirect means. These changes in cortical function might be usefully combined with those brought about by sensorimotor retraining programs, but such studies are awaited.     

Bilateral activation of the trigeminothalamic tract by acute orofacial cutaneous and muscle pain in humans

The conscious perception of somatosensory stimuli is thought to be located in the contralateral cerebral cortex. However, recent human brain imaging investigations in the spinal system report bilateral primary somatosensory cortex (SI) activations during unilateral noxious stimuli and that this ipsilateral spinal representation may be independent of transcallosal connections. In the trigeminal system, there is primate evidence for an ipsilateral somatosensory pathway through the thalamus to the face SI. However, the organization of the trigeminal nociceptive pathway in the human is not clear. The aim of this study was to determine whether noxious stimuli applied to the face are transmitted to the cerebral cortex by bilateral pathways. We used functional magnetic resonance imaging (fMRI) to compare ipsilateral and contralateral activation of the thalamus, SI and secondary somatosensory cortex (SII) during muscle and cutaneous orofacial pain and innocuous facial stimulation in healthy human subjects. We found that both muscle and cutaneous noxious stimuli, from injections of hypertonic saline into the right masseter or overlying skin, evoked bilateral increases in signal intensity in the region encompassing the ventral posterior thalamus as well as the face region of SI and SII. In contrast, innocuous unilateral brushing of the lower lip evoked a strict contralateral ventroposterior thalamic activation, but bilateral activation of SI and SII. These data indicate that, in contrast to innocuous inputs from the face, noxious information ascends bilaterally to the face SI through the ventroposterior thalamus in humans.     

Fingertip Representation in the Human Somatosensory Cortex: An fMRI Study

Eight right-handed adult humans underwent functional magnetic resonance imaging (fMRI) of their brain while a vibratory stimulus was applied to an individual digit tip (digit 1, 2, or 5) on the right hand. Multislice echoplanar imaging techniques were utilized during digit stimulation to investigate the organization of the human primary somatosensory (SI) cortex, cortical regions located on the upper bank of the Sylvian fissure (SII region), insula, and posterior parietal cortices. Thettest and cluster size analyses were performed to produce cortical activation maps, which exhibited significant regions of interest (ROIs) in all four cortical regions investigated. The frequency of significant ROIs was much higher in SI and the SII region than in the insula and posterior parietal region. Multiple digit representations were observed in the primary somatosensory cortex, corresponding to the four anatomic subdivisions of this cortex (areas 3a, 3b, 1, and 2), suggesting that the organization of the human somatosensory cortex resembles that described in other primates. Overall, there was no simple medial to lateral somatotopic representation in individual subject activity maps. However, the spatial distance between digit 1 and digit 5 cortical representations was the greatest in both SI and the SII region within the group. Statistical analyses of multiple activity parameters showed significant differences between cortical regions and between digits, indicating that vibrotactile activations of the cortex are dependent on both the stimulated digit and cortical region investigated.     

Cortical Reorganization in Primary Somatosensory Cortex in Patients With Unilateral Chronic Pain

Bodily representations of the primary somatosensory (SI) cortex are constantly modified according to sensory input. Increased input due to training as well as loss of input due to deafferentation are reflected as changes in the extent of cortical representations. Recent studies in complex regional pain syndrome (CRPS) patients have indicated that the chronic pain itself is associated with cortical reorganization. However, it is unclear whether the observed reorganization is specific for CRPS or if it can be detected also in other types of chronic pain. We therefore searched for signs of cortical reorganization in a group of 8 patients who suffered from chronic pain associated with herpes simplex virus infections. The pain was widespread but restricted to unilateral side of the body and included the upper limb. We recorded neuromagnetic responses to tactile stimulation of fingers of both hands in patients and in a group of healthy, matched control subjects. In the patients, the distance between the thumb (D1) and little finger (D5) representations in SI cortex was statistically significantly smaller in the hemisphere contralateral to painful side than in the hemisphere contralateral to healthy side. In the control subjects, the D1–D5 distance was the same in both hemispheres.PerspectiveThe present results indicate that cortical reorganization occurs in chronic neuropathic pain patients even without peripheral nerve damage. It is possible that cortical reorganization is related to chronic pain, regardless of its etiology. Causality between reorganization and chronic pain should be examined further to develop therapeutic approaches for chronic pain.     

正常人三种模式手指运动时脑激活区域的功能磁共振研究

目的　研究简单动作 (反复连续的手指对指动作 )、随意动作 (抓物体 )和假想动作三种运动模式时 ,脑功能区域的活动机制。方法　利用功能磁共振 (fMRI)影像技术分别摄取 1 0例正常人的利手和非利手在不同运动模式下的双侧脑激活区域 ,再进行机制分析。结果　随意动作时 ,脑同侧激活区的数目多于简单动作 (P <0 .0 5) ,而对侧无明显差异。在简单动作和随意动作中 ,无论利手或非利手 ,主要的激活区为对侧的初级感觉运动皮质 (SM1 ) ,但非利手也可激活同侧少量的SM1。另外 ,脑双侧辅助运动区 (SMA)、前运动区 (PMA) ,对侧顶上小叶 ,同侧小脑也有明显激活 ;偶见基底节激活。假想动作时主要激活额上回、额中回、顶上小叶 ,另见少量扣带回、小脑、脑干、中央旁小叶、基底节处激活。结论　利手的简单动作支配主要在对侧脑SM1 ,而双侧的SM1参与了非利手的简单动作。随意动作属于复杂动作 ,参与动作的区域多于简单动作 ,且双侧SMA均参与 ,可能与双手协调、记忆动作模式的选择、动作顺序的执行有关。假想动作时主要由SMA、PMA支配。该机制对脑卒中的运动训练具有指导意义     

Kinematic specificity of cortical reorganization associated with motor training

Motor training consisting of repetition of directionally specific voluntary thumb movements elicits a short-term memory trace that encodes the kinematic details of the practiced motions in the primary motor cortex. Here, we studied activation patterns associated with this form of training using functional magnetic resonance imaging under careful monitoring of motor training kinematics and electromyography. We identified task-specific reductions in activation in contralateral motor cortex, a region that controls executive motor output, as well as somatosensory cortex and inferior parietal lobule, regions in charge of monitoring motor training kinematics. Our findings are consistent with the hypothesis that a short training period consisting of repetition of finger motions leads to cortical reorganization characterized by a smaller and more efficient network that is specific for the trained movement direction.     

Finger representations in human primary somatosensory cortex as revealed by high-resolution functional MRI of tactile stimulation

Fine-scale functional organization of the finger areas in the human primary somatosensory cortex was investigated by high-resolution BOLD MRI at 3 T using a multi-echo FLASH sequence with a voxel size of 2 mm(3). In six subjects independent tactile stimulation of the distal phalanx of the fingers of the right hand resulted in small circumscribed and barely overlapping activations precisely located along the posterior wall of the central sulcus. Three out of six subjects showed a complete succession of activation sites for all five fingers. The maps also allowed for the identification of individual variations in finger somatotopy. When registered onto the individual high-resolution MRI anatomy and compared with cytoarchitectonical maps, the finger representations were confirmed to lie within Brodmann area 3b as the main input region of the primary somatosensory cortex.