Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in the human somatosensory cortex

High-frequency potential oscillations in the range of 300–900 Hz have recently been shown to concur with the primary response (N20) of the somatosensory cortex in awake humans. However, the physiological mechanisms of the high-frequency oscillations remained undetermined. We addressed the issue by analyzing magnetic fields during wakefulness and sleep over the left hemisphere to right median nerve stimulation with a wide bandpass (0.1–2000 Hz) recording with subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. With wide bandpass recordings, high-frequency magnetic oscillations with the main signal energy at 580–780 Hz were superimposed on the N20m during wakefulness. Isofield mapping at each peak of the high-pass filtered and isolated high-frequency oscillations showed a dipolar pattern and the estimated source for these peaks was the primary somatosensory cortex (area 3b) very close to that for the N20m peak. During sleep, the high-frequency oscillations showed dramatic diminution in amplitude while the N20m amplitude exhibited a moderate increment. This reciprocal relation between the high-frequency oscillations and the N20m during a wake-sleep cycle suggests that they represent different generator substrates. We speculate that the high-frequency oscillations represent a localized activity of the GABAergic inhibitory interneurons of layer 4, which have been shown in animal experiments to respond monosynaptically to thalamo-cortical input with a high-frequency (600–900 Hz) burst of short duration spikes. On the other hand, the underlying N20m represents activity of pyramidal neurons which receive monosynaptic excitatory input from the thalamus as well as a feed-forward inhibition from the interneurons.     

Single-sweep cortical somatosensory evoked potentials: N20 and evoked bursts in sevoflurane anaesthesia

Cortical evoked responses to median nerve stimulation were recorded from 21 subjects during sevoflurane anaesthesia at the level of burst suppression in EEG. The N20/P22 wave had the typical form of a negative wave postcentrally, and positive precentrally. The amplitude exceeded 4 μV in all patients, making it easily visible without averaging on the low-amplitude suppression. These results show that two kinds of somatosensory evoked potential can be studied without averaging during EEG suppression in deep anaesthesia. One is the localised N20/P22 wave, which is seen regularly during suppression after stimuli with intervals exceeding 1 s. The other is the burst, involving the whole cortex, which is not evoked by every stimulus. We suggest that somatosensory evoked potentials can be monitored during sevoflurane-induced EEG suppression, and often can be evaluated reliably from a couple of single sweeps with stimulation interval exceeding 1 s. The enhancement of early cortical components of SEP, their adaptation to repeated stimuli, and the disappearance of later polysynaptic components during EEG suppression, give new possibilities to study the generators of SEP and the different effects of anaesthetics.     

Physiological and pathological oscillatory networks in the human motor system.

Human brain functions are heavily contingent on neural interactions both at the single neuron and the neural population or system level. Accumulating evidence from neurophysiological studies strongly suggests that coupling of oscillatory neural activity provides an important mechanism to establish neural interactions. With the availability of whole-head magnetoencephalography (MEG) macroscopic oscillatory activity can be measured non-invasively from the human brain with high temporal and spatial resolution. To localise, quantify and map oscillatory activity and interactions onto individual brain anatomy we have developed the 'dynamic imaging of coherent sources' (DICS) method which allows to identify and analyse cerebral oscillatory networks from MEG recordings. Using this approach we have characterized physiological and pathological oscillatory networks in the human sensorimotor system. Coherent 8 Hz oscillations emerge from a cerebello-thalamo-premotor-motor cortical network and exert an 8 Hz oscillatory drive on the spinal motor neurons which can be observed as a physiological tremulousness of the movement termed movement discontinuities. This network represents the neurophysiological substrate of a discrete mode of motor control. In parkinsonian resting tremor we have identified an extensive cerebral network consisting of primary motor and lateral premotor cortex, supplementary motor cortex, thalamus/basal ganglia, posterior parietal cortex and secondary somatosensory cortex, which are entrained in the tremor or twice the tremor rhythm. This low frequency entrapment of motor areas likely plays an important role in the pathophysiology of parkinsonian motor symptoms. Finally, studies on patients with postural tremor in hepatic encephalopathy revealed that this type of tremor results from a pathologically slow thalamocortical and cortico-muscular coupling during isometric hold tasks. In conclusion, the analysis of oscillatory cerebral networks provides new insights into physiological mechanisms of motor control and pathophysiological mechanisms of tremor disorders.     

Modelling of cortical and thalamic 600 Hz activity by means of oscillatory networks

The purpose of this study is to investigate information processing in the primary somatosensory system with the help of oscillatory network modelling. Specifically, we consider interactions in the oscillatory 600 Hz activity between the thalamus and the cortical Brodmann areas 3b and 1. This type of cortical activity occurs after electrical stimulation of peripheral nerves such as the median nerve. Our measurements consist of simultaneous 31-channel MEG and 32-channel EEG recordings and individual 3D MRI data. We perform source localization by means of a multi-dipole model. The dipole activation time courses are then modelled by a set of coupled oscillators, described by linear second-order ordinary delay differential equations (DDEs). In particular, a new model for the thalamic activity is included in the oscillatory network. The parameters of the DDE system are successfully fitted to the data by a nonlinear evolutionary optimization method. To activate the oscillatory network, an individual input function is used, based on measurements of the propagated stimulation signal at the biceps. A significant feedback from the cortex to the thalamus could be detected by comparing the network modelling with and without feedback connections. Our finding in humans is supported by earlier animal studies. We conclude that this type of rhythmic brain activity can be modelled by oscillatory networks in order to disentangle feed forward and feedback information transfer.     

Somatotopy of human hand somatosensory cortex revealed by dipole source analysis of early somatosensory evoked potentials and 3D-NMR tomography

Somatosensory evoked potentials (SEPs) to median nerve and finger stimulation were analyzed by means of spatio-temporal dipole modelling combined with 3D-NMR tomography in 8 normal subjects. The early SEPs were modelled by 3 equivalent dipoles located in the region of the brain-stem (B) and in the region of the contralateral somatosensory cortex (T and R). Dipole B explained peaks P14 and N18 at the scalp. Dipole T was tangentially oriented and explained the N20-P20, dipole R was radially oriented and modelled the P22. The tangential dipole sources T were located within a distance of 6 mm on the average and all were less than 9 mm from the posterior bank of the central sulcus. In 6 subjects the tangential sources related to finger stimulation arranged along the central sulcus according to the known somatotopy. The radial sources did not show a consistent somatotopic alignment across subjects. We conclude that the combination of dipole source analysis and 3D-NMR tomography is a useful tool for functional localization within the human hand somatosensory cortex.     

Coupled oscillators for modeling and analysis of EEG/MEG oscillations.

This study presents three EEG/MEG applications in which the modeling of oscillatory signal components offers complementary analysis and an improved explanation of the underlying generator structures. Coupled oscillator networks were used for modeling. Parameters of the corresponding ordinary coupled differential equation (ODE) system are identified using EEG/MEG data and the resulting solution yields the modeled signals. This model-related analysis strategy provides information about the coupling quantity and quality between signal components (example 1, neonatal EEG during quiet sleep), allows identification of the possible contribution of hidden generator structures (example 2, 600-Hz MEG oscillations in somatosensory evoked magnetic fields), and can explain complex signal characteristics such as amplitude-frequency coupling and frequency entrainment (example 3, EEG burst patterns in sedated patients).     

Unmasking of cortical SEP components by changes in stimulus rate: a topographic study

We performed topographic mapping of somatosensory responses to median nerve stimulation delivered at 2, 5 and 10 Hz. Parietal N20 was significantly attenuated in 10 Hz somatosensory evoked potentials (SEPs), while central P22 diminished between 2 and 5 Hz, remaining stable thereafter. The single component most affected by increasing stimulus rate was N30, which abated by more than 50% in 10 Hz SEPs, as compared with basal responses. N30 attenuation disclosed the existence of an earlier negative component, N24, which appeared as a notch on the N30 ascending slope in 2 Hz SEPs, but became a well-defined peak at higher stimulus rates. The N24 negativity was not significantly modified by stimulus rate; it had a parietal counterpart (P24) with the same peak latency and identical behavior during the experimental procedure. Both P24 and N24 could be differentiated from central P22 on the basis of topographical distribution and response to stimulus frequency. P22 topography could be the result of a radially oriented generator, while P24/N24 appeared as the two poles of a neural source tangential to the scalp. P27 was seen in 40% of the subjects only; it is suggested that P27 is itself a composite potential to which the generator of N30 could contribute in part. We conclude that there is no single “optimal” stimulation rate for SEP recording. On the contrary, combination of different frequencies of stimulation should enhance the diagnostic utility of this technique by allowing a more selective assessment of overlapping activities.     

Three-dimensional human somatosensory evoked potentials

Median nerve somatosensory evoked potentials were recorded from 30 normal adults using conventional scalp derivations and an orthogonal bipolar surface electrode montage. This allowed the determination of the spatial orientation of the hypothetical centrally located equivalent dipole derived from the evoked response recorded in 3-dimensional voltage space. The 3-dimensional voltage trajectory describing changes in equivalent dipole orientation and magnitude revealed 4 major apices between 5 and 25 msec, 3 of which corresponded to the traditional P14, N20 and P25 peaks. A fourth apex at 17 msec was not as evident in the conventional recordings and signaled a transition from a vertical P14–N18 generator process to a horizontal N20 generator process. The normal within- and between-subject variability of trajectory apices, segments and planes are described, along with the theoretical and practical implications of this recording technique.     

Modelling and detecting deep brain activity with MEG and EEG

We introduce an anatomical and electrophysiological model of deep brain structures dedicated to magnetoencephalography (MEG) and electroencephalography (EEG) source imaging. So far, most imaging inverse models considered that MEG/EEG surface signals were predominantly produced by cortical, hence superficial, neural currents. Here we question whether crucial deep brain structures such as the basal ganglia and the hippocampus may also contribute to distant, scalp MEG and EEG measurements. We first design a realistic anatomical and electrophysiological model of these structures and subsequently run Monte-Carlo experiments to evaluate the respective sensitivity of the MEG and EEG to signals from deeper origins. Results indicate that MEG/EEG may indeed localize these deeper generators, which is confirmed here from experimental MEG data reporting on the modulation of alpha (10–12 Hz) brain waves.     

Steady-state analysis of somatosensory evoked potentials

We report the development of a new method for frequency domain analysis of steady-state somatosensory evoked potentials (SEPs) to amplitude-modulated electrical stimulation, which can be recorded in significantly less time than traditional SEPs. Resampling techniques were used to compare the steady-state SEP to traditional SEP recordings, which are based on signal averaging in the time domain of cortical responses to repetitive transient stimulation and take 1–2 min or more to obtain a satisfactory signal/noise ratio. Median nerves of 3 subjects were stimulated continuously with electrical alternating current at several modulation frequencies from 7 to 41 Hz. Amplitude modulation was used to concentrate the power in higher frequencies, away from the modulation frequency, to reduce the amount of stimulus artifact recorded. Data were tested for signal detectability in the frequency domain using the T_circ² statistic. A reliable steady-state response can be recorded from scalp electrodes overlying somatosensory cortex in only a few seconds. In contrast, no signal was statistically discriminable from noise in the transient SEP from as much as 20 s of data. This dramatic time savings accompanying steady-state somatosensory stimulation may prove useful for monitoring in the operating room or intensive care unit.     

SEPs to finger joint input lack the N20-P20 response that is evoked by tactile inputs: contrast between cortical generators in areas 3b and 2 in humans

A method using a DC servo motor is described to produce brisk angular movements at finger interphalangeal joints in humans. Small passive flexions of 2° elicited sizable somatosensory evoked potentials (SEPs) starting with a contralateral positive P34 parietal response thought to reflect activation of a radial equivalent dipole generator in area 2 which receives joint inputs. By contrast, electric stimulation of tactile (non-joint) inputs from the distal phalanx evoked the usual contralateral negative N20 reflecting a tangential equivalent dipole generator in area 3b. Finger joint inputs also evoked a precentral positivity equivalent to the P22 of motor area 4, and a large frontal negativity equivalent to N30. It is suggested that natural stimulation allows human SEP components to the differentiated in conjunction with distinct cortical somatotopic projections.     

Statistical Analysis of Sleep Spindle Occurrences

Spindles - a hallmark of stage II sleep - are a transient oscillatory phenomenon in the EEG believed to reflect thalamocortical activity contributing to unresponsiveness during sleep. Currently spindles are often classified into two classes: fast spindles, with a frequency of around 14 Hz, occurring in the centro-parietal region; and slow spindles, with a frequency of around 12 Hz, prevalent in the frontal region. Here we aim to establish whether the spindle generation process also exhibits spatial heterogeneity. Electroencephalographic recordings from 20 subjects were automatically scanned to detect spindles and the time occurrences of spindles were used for statistical analysis. Gamma distribution parameters were fit to each inter-spindle interval distribution, and a modified Wald-Wolfowitz lag-1 correlation test was applied. Results indicate that not all spindles are generated by the same statistical process, but this dissociation is not spindle-type specific. Although this dissociation is not topographically specific, a single generator for all spindle types appears unlikely.     

Presurgical functional localization of primary somatosensory cortex by dipole tracing method of scalp-skull-brain head model applied to somatosensory evoked potential

The aim of the present study was to explore the utility of dipole tracing (DT) of a scalp-skull-brain (SSB) head model in preoperative functional localization of the human brain. Nine patients who underwent surgery of mass lesions around the central sulcus (CS) were employed. By using SSB/DT, dipole source location of early cortical components of the somatosensory evoked potential (SEP) was estimated before surgery. Motor cortex, CS and primary somatosensory cortex were determined by cortical SEP during surgery. After surgery precise functional mapping was reproduced in MRI, and the accuracy of DT was evaluated by measuring the distance between estimated dipole source and the posterior bank of the CS. We defined this distance as localization error of DT. In 4 cases without structural change around the sensorimotor cortex, localization error ranged from 1 to 4 mm with an average of 2 mm. In 5 cases with structural alteration of sensorimotor cortex, localization error ranged from 6 to 10 mm with an average of 8 mm. The difference in localization error between the two groups was statistically significant, and may have been caused by changes of conductance near sensorimotor cortex in the latter group. Functional localization by DT was accurate and useful. But localization error could not be ignored in cases with structural alteration in the sensorimotor cortex.     

Neural generators of early cortical somatosensory evoked potentials in the awake monkey

Controversy continues to exist regarding the generators of the initial cortical components of the somatosensory evoked potential (SEP). This issue was explored by detailed epidural and intracortical mapping of somatosensory evoked activity in Old World monkeys. In depth recordings, 3 complementary procedures were utilized: (1) the intracortical and subcortical distribution of SEPs was determined from approximately 4000 locations; (2) concomitant profiles of multiple unit activity (MUA) were recorded as an estimate of local action potential profiles; (3) 1-dimensional calculations of current source density (CSD) were used to outline the timing and pattern of regional transmembrane current flow. Our analysis confirms the participation of multiple cortical areas, located on either side of the central sulcus, in the generation of the initial cortical SEP components. Earliest activity, P10, was localized to area 3, followed within milliseconds by activation of areas 1, 2 (P12), and 4 (P13). In SI (Brodmann's areas 3, 1 and 2), the initial SEP components reflect the depolarization of lamina 4 stellate cells and the subsequent activation of adjacent pyramidal cells in laminae 3 and 5. The genesis of later cortical components (P20, N45) represents the composite of activity distributed across multiple cortical laminae and the interaction of overlapping excitatory and inhibitory events. These findings have direct implications for the clinical interpretation of SEP waveforms.     

Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background

Sleep spindles are ∼1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phase-locked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators.

Methodology/Principal Findings

We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere.

Conclusions/Significance

The heterogeneity of MEG sources implies that multiple generators are active during human sleep spindles. If the source modeling is correct, then EEG spindles are generated by a different, diffusely synchronous system. Animal studies have identified two thalamo-cortical systems, core and matrix, that produce focal or diffuse activation and thus could underlie MEG and EEG spindles, respectively. Alternatively, EEG spindles could reflect overlap at the sensors of the same sources as are seen from the MEG. Although our results generally match human intracranial recordings, additional improvements are possible and simultaneous intra- and extra-cranial measures are needed to test their accuracy.     

Rapid-Rate Paired Associative Stimulation over the Primary Somatosensory Cortex

Rapid-rate paired associative stimulation (rPAS) involves repeat pairing of peripheral nerve stimulation and Transcranial magnetic stimulation (TMS) pulses at a 5 Hz frequency. RPAS over primary motor cortex (M1) operates with spike-timing dependent plasticity such that increases in corticospinal excitability occur when the nerve and TMS pulse temporally coincide in cortex. The present study investigates the effects of rPAS over primary somatosensory cortex (SI) which has not been performed to date. In a series of experiments, rPAS was delivered over SI and M1 at varying timing intervals between the nerve and TMS pulse based on the latency of the N20 somatosensory evoked potential (SEP) component within each participant (intervals for SI-rPAS: N20, N20-2.5 ms, N20 + 2.5 ms, intervals for M1-rPAS: N20, N20+5 ms). Changes in SI physiology were measured via SEPs (N20, P25, N20-P25) and SEP paired-pulse inhibition, and changes in M1 physiology were measured with motor evoked potentials and short-latency afferent inhibition. Measures were obtained before rPAS and at 5, 25 and 45 minutes following stimulation. Results indicate that paired-pulse inhibition and short-latency afferent inhibition were reduced only when the SI-rPAS nerve-TMS timing interval was set to N20-2.5 ms. SI-rPAS over SI also led to remote effects on motor physiology over a wider range of nerve-TMS intervals (N20-2.5 ms – N20+2.5 ms) during which motor evoked potentials were increased. M1-rPAS increased motor evoked potentials and reduced short-latency afferent inhibition as previously reported. These data provide evidence that, similar to M1, rPAS over SI is spike-timing dependent and is capable of exerting changes in SI and M1 physiology.     

Flexibility in the patterning and control of axial locomotor networks in lamprey

In lower vertebrates, locomotor burst generators for axial muscles generally produce unitary bursts that alternate between the two sides of the body. In lamprey, a lower vertebrate, locomotor activity in the axial ventral roots of the isolated spinal cord can exhibit flexibility in the timings of bursts to dorsally-located myotomal muscle fibers versus ventrally-located myotomal muscle fibers. These episodes of decreased synchrony can occur spontaneously, especially in the rostral spinal cord where the propagating body waves of swimming originate. Application of serotonin, an endogenous spinal neurotransmitter known to presynaptically inhibit excitatory synapses in lamprey, can promote decreased synchrony of dorsal-ventral bursting. These observations suggest the possible existence of dorsal and ventral locomotor networks with modifiable coupling strength between them. Intracellular recordings of motoneurons during locomotor activity provide some support for this model. Pairs of motoneurons innervating myotomal muscle fibers of similar ipsilateral dorsoventral location tend to have higher correlations of fast synaptic activity during fictive locomotion than do pairs of motoneurons innervating myotomes of different ipsilateral dorsoventral locations, suggesting their control by different populations of premotor interneurons. Further, these different motoneuron pools receive different patterns of excitatory and inhibitory inputs from individual reticulospinal neurons, conveyed in part by different sets of premotor interneurons. Perhaps, then, the locomotor network of the lamprey is not simply a unitary burst generator on each side of the spinal cord that activates all ipsilateral body muscles simultaneously. Instead, the burst generator on each side may comprise at least two coupled burst generators, one controlling motoneurons innervating dorsal body muscles and one controlling motoneurons innervating ventral body muscles. The coupling strength between these two ipsilateral burst generators may be modifiable and weakening when greater swimming maneuverability is required. Variable coupling of intrasegmental burst generators in the lamprey may be a precursor to the variable coupling of burst generators observed in the control of locomotion in the joints of limbed vertebrates.     

Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation

Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA_SEP(N20) and HFA_SEP(N80)) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA_CCEP(N1) and HFA_CCEP(N2)). HFA_SEP(N20) showed the power peak in the frequency above 200 Hz, while HFA_CCEP(N1) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA_CCEP(N1) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.     

Replicability of MEG and EEG measures of the auditory N1/N1m-response

We investigated the replicability of the source location, amplitude and latency measures of the auditory evoked N1 (EEG) and N1m (MEG) responses. Each of the 5 subjects was measured 6 times in two recording sessions. Responses to monaural stimuli were recorded from 122 MEG and 64 EEG channels simultaneously. The EEG data were modeled with a symmetrically-located dipole pair. For the MEG data, one dipole in each hemisphere was located independently using a subset of channels. Standard deviation (SD) was used as a measure for replicability. The average SD of the x, y and z coordinates of the contralateral N1m dipole was about 2 mm, whereas the corresponding figures for the ipsilateral N1m and the contra- and ipsilateral N1 were about twice as large. The SDs of the dipole amplitudes and latencies were almost equal with MEG and EEG. The amplitude and latency measures of the MEG field gradient waveforms were almost as replicable as those of the dipole models. The results suggest that both MEG and EEG can be used for investigating the simultaneous activity of the left and right auditory cortices independently, MEG being superior in certain experimental setups.     

Oscillatory coupling in writing and writer's cramp.

Writing is a highly skilled and overlearned movement. In patients suffering from writer's cramp, a focal task-induced dystonia, writing is impaired or even impossible due to involuntary muscle contractions and abnormal posture, which occur as soon as the person picks up a pen or within writing a few words. The underlying pathophysiological mechanisms of this movement disorder are not fully understood up to now. The aim of the present study was to unravel the oscillatory network underlying physiological writing in healthy subjects and dystonic writing in writer's cramp patients. Using whole-head magnetoencephalography (MEG) and the analysis tool dynamic imaging of coherent sources (DICS) we studied oscillatory neural coupling during writing in eleven healthy subjects and eight patients suffering from writer's cramp. Simultaneous recording of brain activity with MEG and activity of forearm and hand muscles with surface electromyography (EMG) was performed while subjects were writing for five minutes with their dominant right hand. Applying DICS sources of strongest cerebro-muscular coherence and cerebro-cerebral coherence during writing were identified, which consistently included six brain areas in both, the control subjects and the patients: contralateral and ipsilateral sensorimotor cortex, ipsilateral cerebellum, contralateral thalamus, contralateral premotor and posterior parietal cortex. Coherence between cortical sources and muscles appeared primarily in the frequency of writing movements (3-7 Hz) while coherence between cerebral sources occurred primarily around 10 Hz (8-13 Hz). Interestingly, consistent coupling between both sensorimotor cortices was observed in patients only, whereas coupling between ipsilateral cerebellum and the contralateral posterior parietal cortex was found in control subjects only. These results are consistent with the often described bilateral pathophysiology and impaired sensorimotor integration in writer's cramp patients.