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Biomedical subjects

C Gerloff

Publications and source records attributed to C Gerloff.

At least 19 recordsLinked to original sources

PET study of visually and non-visually guided finger movements in patients with severe pan-sensory neuropathies and healthy controls.

Although patients with sensory neuropathies and normal muscle power are rare, they have been extensively studied because they are a model for dissociating the sensory and motor components of movement. We have examined these patients to determine the cerebral functional anatomy of movement in the absence of proprioceptive input. In addition, the disabling symptoms of these patients can be substantially improved by visually monitoring their movements. We hypothesized that, during visually guided movements, these patients would show overactivity of regions specialized for visuomotor control with the possible additional involvement of areas that normally process somatosensory information. We used positron emission tomography (PET) and the tracer H(2)(15)O to determine the functional anatomy of visually and non-visually guided finger movements in three patients with long-standing pan-sensory neuropathies and normal muscle power and six healthy controls. Five conditions were performed with the right hand: a sequential finger movement task under visual guidance, the same motor task without observation of the hand, monitoring a video of the same sequential finger movement, a passive visual task observing a reversing checkerboard, and an unconstrained rest condition. Data were analyzed using conventional subtraction techniques with a statistical threshold of z>2.33 with corrections for multiple comparisons. When compared with the control group, activation was not deficient in any brain areas of the patient cohort in any of the contrasts tested. In particular, in the non-visually guided movement task, in which meaningful visual and proprioceptive input was absent, the patient group activated primary motor, premotor, and cerebellar regions. This suggests that these areas are involved in motor processing independent of sensory input. In all conditions involving visual observation of hand movements, there was highly significant overactivity of the left parietal operculum (SII) and right parieto-occipital cortex (PO) in the patient group. Recent non-human primate studies have suggested that the PO region contains a visual representation of hand movements. Overactivity of this area and the activation of SII by visual input appear to indicate that compensatory overactivity of visual areas and cross-modal plasticity of somatosensory areas occur in deafferented patients. These processes may underlie their ability to compensate for their proprioceptive deficits.

Aged

Functional coupling of human cortical sensorimotor areas during bimanual skill acquisition.

Bimanual co-ordination of skilled finger movements is a high-level capability of the human motor system and virtually always requires training. Little is known about the physiological processes underlying successful bimanual performance and skill acquisition. In the present study, we used task-related coherence (TRCoh) and task-related power (TRPow) analysis of multichannel surface EEG to investigate the functional coupling and regional activation of human sensorimotor regions during bimanual skill acquisition. We focused on changes in interhemispheric coupling associated with bimanual learning. TRCoh and TRPow were estimated during the fusion of two overlearned unimanual finger-tapping sequences into one novel bimanual sequence, before and after a 30-min training period in 18 normal volunteers. Control experiments included learning and repetition of complex and simple unimanual finger sequences. The main finding was a significant increase in interhemispheric TRCoh selectively in the early learning stage (P < 0.0001). Interhemispheric TRCoh was also present during the unimanual control tasks, but with lower magnitude, even if learning was involved. Training improved bimanual sequence performance (from 58.3+/-24.1 to 83.7+/-15.3% correct sequences). After training, interhemispheric (bimanual) TRCoh decreased again, thereby approaching levels similar to those in the unimanual controls. We propose that the initial increase in TRCoh reflects changes in interhemispheric communication that are specifically related to bimanual learning and may be relayed through the corpus callosum. The present data might also offer a neurophysiological explanation for the clinical observation that patients with lesions of the corpus callosum may show deficits in the acquisition of novel bimanual tasks but not necessarily in the execution of previously learned bimanual activities.

Adult

Movement-related cerebellar activation in the absence of sensory input.

Movement-related cerebellar activation may be due to sensory or motor processing. Ordinarily, sensory and motor processing are obligatorily linked, but in patients who have severe pansensory neuropathies with normal muscle strength, motor activity occurs in isolation. In the present study, positron emission tomography and functional magnetic resonance imaging in such patients showed no cerebellar activation with passive movement, whereas there was prominent movement-related cerebellar activation despite absence of proprioceptive or visual input. The results indicate that motor processing occurs within the cerebellum and do not support the recently advanced view that the cerebellum is primarily a sensory organ.

Aged

Inhibitory influence of the ipsilateral motor cortex on responses to stimulation of the human cortex and pyramidal tract.

1. The ability of the primary motor cortex (M1) to modulate motor responses in ipsilateral hand muscles seems to be important for normal motor control and potentially also for recovery after brain lesions. It is not clear which pathways mediate this ipsilateral modulation. Transcallosal connections have been proposed, but are known to be sparse between cortical hand motor representations in primates. The present study was performed to determine whether descending ipsilateral modulation of motor responses might also be mediated below the cortical level in humans. 2. A paired-pulse protocol was used, in which motor-evoked potentials (MEPs) were produced by cortical transcranial magnetic stimulation (cTMS) or by electrical stimulation of the pyramidal tract at the level of the pyramidal decussation (pdTES), in both preactivated and relaxed hand muscles. Paired stimuli were applied at various interstimulus intervals (ISIs) between 2 and 100 ms. The conditioning stimulus (CS) was always magnetic, and delivered to the M1 ipsilateral to the target hand, prior to the test stimulus (TS). The magnetic TS was delivered to the M1 contralateral to the target hand; the electrical TS was applied through electrodes placed over the mastoid process bilaterally. Further experiments included cortical electrical stimulation and H-reflexes. The MEP amplitudes were averaged separately for each ISI and the control condition (no CS), and expressed as a percentage of the unconditioned response. 3. Conditioning stimulation of the ipsilateral M1 resulted in significant inhibition of magnetically evoked MEPs, and also of MEPs produced by pdTES. Inhibition occurred at ISIs between 6 and 50 ms, and was observed in preactivated and relaxed muscles. Higher CS intensities caused greater inhibition of both cTMS- and pdTES-evoked MEPs. 4. While the conditioning effects on magnetically evoked muscle responses could be explained by a transcallosal mechanism, the effects on pdTES-evoked MEPs cannot, because they are elicited subcortically and are therefore not susceptible to inhibitory mechanisms transmitted at the cortico-cortical level. 5. In conclusion, the present results provide novel evidence that the inhibitory influence of the human M1 on ipsilateral hand muscles is to a significant extent mediated below the cortical level, and not only through cortico-cortical transcallosal connections. They point to a concept of inhibitory interaction between the two primary motor cortices that is relayed at multiple levels along the neuroaxis, thus perhaps providing a structurally redundant system which may become important in case of lesions.

Adult

Cutaneous withdrawal reflexes of the upper extremity.

We characterized reflexes of the upper limb elicited by electrical stimulation of the fingers. Surface electromyogram (EMG) was recorded from several upper extremity muscles, and a finger was stimulated through paired ring electrodes. A train of 4-10 shocks at a frequency of 300 Hz and an intensity 4-6 times the perceptual threshold was the most effective stimulus for evoking EMG activity in relaxed arm muscles. Habituation was prominent. Latencies of EMG activity were <100 ms for most proximal and forearm muscles, and at least 40 ms prior to voluntary withdrawal movements. The timing of EMG activity in arm muscles was similar to that of the E2 component of the cutaneomuscular reflex evoked in these same muscles during contraction, and coincided with a silent period in active hand muscles. We conclude that cutaneous stimuli to the fingers activate a complex motor pattern that tends to withdraw the hand at the same time the grasp is released.

Adult

Abnormal somatosensory homunculus in dystonia of the hand.

Abnormalities of the sensory system have been proposed as causative factors for dystonia By mapping the human cortical hand somatosensory area of 6 patients with focal dystonia of the hand, we found an abnormality of the normal homuncular organization of the finger representations in the primary somatosensory cortex (S1). Although a remote antecedent event or even a developmental anomaly cannot entirely be ruled out, our findings may support the concept that abnormal plasticity is involved in the development of dystonia.

Brain

Cortical activation during fast repetitive finger movements in humans: steady-state movement-related magnetic fields and their cortical generators.

OBJECTIVE: To study the cortical physiology of fast repetitive finger movements. METHODS: We recorded steady-state movement-related magnetic fields (ssMRMFs) associated with self-paced, repetitive, 2-Hz finger movements in a 122-channel whole-head magnetometer. The ssMRMF generators were determined by equivalent current dipole (ECD) modeling and co-registered with anatomical magnetic resonance images (MRIs). RESULTS: Two major ssMRMF components occurred in proximity to EMG onset: a motor field (MF) peaking at 37+/-11 ms after EMG onset, and a postmovement field (post-MF), with inverse polarity, peaking at 102+/-13 ms after EMG onset. The ECD for the MF was located in the primary motor cortex (M1), and the ECD for the post-MF in the primary somatosensory cortex (S1). The MF was probably closely related to the generation of corticospinal volleys, whereas the post-MF most likely represented reafferent feedback processing. CONCLUSIONS: The present data offer further evidence that the main phasic changes of cortical activity occur in direct proximity to repetitive EMG bursts in the contralateral M1 and S1. They complement previous electroencephalography (EEG) findings on steady-state movement-related cortical potentials (ssMRCPs) by providing more precise anatomical information, and thereby enhance the potential value of ssMRCPs and ssMRMFs for studying human sensorimotor cortex activation non-invasively and with high temporal resolution.

Adult

Functional coupling and regional activation of human cortical motor areas during simple, internally paced and externally paced finger movements.

We studied the activation and interaction of cortical motor regions during simple, internally paced and externally paced right-hand finger extensions in healthy volunteers. We recorded EEGs from 28 scalp electrodes and analysed task-related coherence, task-related power and movement-related cortical potentials. Task-related coherence reflects inter-regional functional coupling of oscillatory neuronal activity, task-related power reflects regional oscillatory activity of neuronal assemblies and movement-related cortical potentials reflect summated potentials of apical dendrites of pyramidal cells. A combination of these three analytical techniques allows comprehensive evaluation of different aspects of information processing in neuronal assemblies. For both externally and internally paced finger extensions, movement-related regional activation was predominant over the contralateral premotor and primary sensorimotor cortex, and functional coupling occurred between the primary sensorimotor cortex of both hemispheres and between the primary sensorimotor cortex and the mesial premotor areas, probably including the supplementary motor area. The main difference between the different types of movement pacing was enhanced functional coupling of central motor areas during internally paced finger extensions, particularly inter-hemispherically between the left and right primary sensorimotor cortexes and between the contralateral primary sensorimotor cortex and the mesial premotor areas. Internally paced finger extensions were also associated with additional regional (premovement) activation over the mesial premotor areas. The maximal task-related coherence differences between internally and externally paced finger extensions occurred in the frequency range of 20-22 Hz rather than in the range of maximal task-related power differences (9-11 Hz). This suggests that important aspects of information processing in the human motor system could be based on network-like oscillatory cortical activity and might be modulated on at least two levels, which to some extent can operate independently from each other: (i) regional activation (task-related power) and (ii) inter-regional functional coupling. We propose that internal pacing of movement poses higher demands on the motor system than external pacing, and that the motor system responds not only by increasing regional activation of the mesial premotor system, including the supplementary motor area, but also by enhancing information flow between lateral and mesial premotor and sensorimotor areas of both hemispheres, even if the movements are simple and unimanual.

Adult

The role of the human motor cortex in the control of complex and simple finger movement sequences.

We evaluated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) at different stimulus intensities on finger sequences of varying complexity. Eighteen subjects played unimanual finger sequences of different complexity on an electronic piano. For each finger sequence, 16 notes were played to the 2 Hz beat of a metronome. After the first four notes, rTMS was applied to the scalp location overlying the hand motor representation for approximately 2 s. Accuracy and timing errors were analysed. Stimulation over the M1 had a differential effect on sequences of different complexity. Stimulus intensities capable of disrupting the performance of a complex sequence did not affect simple sequences. To disrupt simple sequences, the stimulus strength had to be augmented. This effect was characteristic of the contralateral M1 position (five other scalp locations were also stimulated). It is argued that the differential effect of rTMS on simple and complex sequences is probably due to interference with M1 function. Interference with the lateral premotor cortex (PMC) may play an additional role. The particular relevance of the M1 is supported by results in a patient with PMC stroke. The present findings suggest that the human M1 plays a greater role in the performance of complex than of simple finger movement sequences. One possible explanation could be that the human M1 is not only an executive motor area but can also contribute to movement sequence organization.

Acoustic Stimulation

Studies of neuroplasticity with transcranial magnetic stimulation.

In recent years, there has been increasing interest in studies of brain plasticity. Although still loosely defined, this term describes the ability of the brain to change. Cortical plasticity encompasses a wide variety of phenomena and mechanisms, including modifications in cortical properties such as strength of internal connections, representational patterns, or neuronal modifications, either morphological or functional (Donoghue et al., 1996). We focus on the description of different ways in which transcranial magnetic stimulation (TMS) can be used to study patterns of reorganization and some of the mechanisms involved in these changes. Correlation between TMS and neuroimaging studies in humans and animal studies addressing similar questions is discussed. It is important to identify in each situation whether plasticity plays a beneficial role or is maladaptive in terms of functional compensation. The understanding of patterns, mechanisms, and functional relevance of cortical plasticity will hopefully lead to the design of effective strategies to enhance plasticity when it is beneficial and to down-regulate it when it is maladaptive. An example of a possible strategy, using TMS, is discussed.

Blindness

Cortical activation during fast repetitive finger movements in humans: dipole sources of steady-state movement-related cortical potentials.

Fast repetitive finger movements are associated with characteristic EEG patterns described in humans as steady-state movement-related cortical potentials (ssMRCPs). The objective of the present study was to determine the electrical generators of ssMRCPs (movement rate, 2 Hz) by dipole modelling. The generators for the initial ssMRCP phase (peak approximately 60 msec before EMG onset) were located in the central region bilaterally, with largely radial orientation, consistent with activation of the crown of the precentral gyrus. The generator of the next phase (peak approximately 10 msec after EMG onset) was located in the contralateral central region with tangential posterior orientation, consistent with activation of the anterior wall of the central sulcus. The postmovement phase (peak approximately 95 msec after EMG onset) was explained by another source in the contralateral central region with tangential anterior orientation, consistent with activation of the posterior wall of the central sulcus. This pattern probably corresponds to a sequence of activation of the bilateral dorsal premotor cortex, contralateral primary motor, and primary somatosensory cortex that takes place within approximately 200 msec around EMG onset. Steady-state movement-related cortical potentials in combination with dipole modelling provide a novel, noninvasive approach to assessing changes of human cortical premotor, motor, and somatosensory activation in the millisecond range.

Adult

Implicit and explicit learning in an auditory serial reaction time task.

OBJECTIVE: To explore the role of the motor cortex during implicit and explicit learning. MATERIALS AND METHODS: EEG signals were recorded from 30 channels by measuring task-related desynchronization (TRD) when 10 right-handed naive volunteers performed a variation of the serial reaction task. Stimuli, consisting of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented binaurally through a pair of tubephones at 60 dB with a 2-s constant interstimulus interval. A series of 10 repetitive tones represented the test sequence; the random sequence was the control. RESULTS: All subjects developed implicit and explicit knowledge reflected by decreased response time, increased accuracy, and the ability to generate the sequence. Six of 10 subjects demonstrated implicit learning without explicit learning during the first 3 blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a peak amplitude, declining thereafter. CONCLUSIONS: Properties of the sensorimotor cortex change during learning and these changes are independent of stimulus modality.

Adult

Integrative visuomotor behavior is associated with interregionally coherent oscillations in the human brain.

Coherent electrical brain activity has been demonstrated to be associated with perceptual events in mammals. It is unclear whether or not it is also a mechanism instrumental in the performance of sensorimotor tasks requiring the continuous processing of information between primarily executive and receptive brain areas. In particular it is unknown whether or not interregional coherent activity detectable in electroencephalographic (EEG) recordings on the scalp reflects interareal functional cooperativity in humans. We studied patterns of changes in EEG-coherence associated with a visuomotor force-tracking task in seven subjects. Interregional coherence of EEG signals recorded from scalp regions overlying the visual and the motor cortex increased in comparison to a resting condition when subjects tracked a visual target by producing an isometric force with their right index finger. Coherence between visual and motor cortex decreased when the subjects produced a similar motor output in the presence of a visual distractor and was unchanged in a purely visual and purely motor task. Increases and decreases of coherence were best differentiated in the low beta frequency range (13-21 Hz). This observation suggests a special functional significance of low frequency oscillations in information processing in large-scale networks. These findings substantiate the view that coherent brain activity underlies integrative sensorimotor behavior.

Adult

Functional relevance of cross-modal plasticity in blind humans.

Functional imaging studies of people who were blind from an early age have revealed that their primary visual cortex can be activated by Braille reading and other tactile discrimination tasks. Other studies have also shown that visual cortical areas can be activated by somatosensory input in blind subjects but not those with sight. The significance of this cross-modal plasticity is unclear, however, as it is not known whether the visual cortex can process somatosensory information in a functionally relevant way. To address this issue, we used transcranial magnetic stimulation to disrupt the function of different cortical areas in people who were blind from an early age as they identified Braille or embossed Roman letters. Transient stimulation of the occipital (visual) cortex induced errors in both tasks and distorted the tactile perceptions of blind subjects. In contrast, occipital stimulation had no effect on tactile performance in normal-sighted subjects, whereas similar stimulation is known to disrupt their visual performance. We conclude that blindness from an early age can cause the visual cortex to be recruited to a role in somatosensory processing. We propose that this cross-modal plasticity may account in part for the superior tactile perceptual abilities of blind subjects.

Adult

Involvement of the ipsilateral motor cortex in finger movements of different complexities.

Functional imaging and behavioral studies suggest involvement of the ipsilateral hemisphere in hand movements, particularly of the left hand. If this is so, transient disturbance of the motor cortex (M1) with repetitive transcranial magnetic stimulation (rTMS) may affect ipsilateral motor sequences, and the effects may differ on the two sides. We studied 15 right-handed subjects who played a simple and a complex piano sequence for 8 seconds each. Two seconds after the beginning of each sequence, rTMS was delivered to the ipsilateral or contralateral M1, or directed away from the head (control trial). Ipsilateral M1 stimulation on either side induced timing errors in both sequences, and with the complex sequence induced more timing errors in the left hand than in the right hand. Errors of the right hand with both sequences occurred in the stimulation period only, but errors of the left hand with the complex sequence occurred in both the stimulation and poststimulation periods. We conclude that the ipsilateral M1 is involved in fine finger movements. The left hemisphere plays a greater role in timing ipsilateral complex sequences than the right hemisphere and may be more involved in the processing of complex motor programs.

Adult

Steady-state movement-related cortical potentials: a new approach to assessing cortical activity associated with fast repetitive finger movements.

Traditionally, studies of movement-related cortical potentials have focused on the preparation of single self-paced movements performed slowly. We studied MRCPs elicited by metronome-paced, fast repetitive finger movements (2/s) with 28-channel (10 normal subjects) and 122-channel (two subjects) EEG. EMG-locked averaging of 500 ms time windows (300 ms before to 200 ms after each EMG onset) produced a distinct pattern of phasic MRCPs (steady-state MRCPs). The main components were a pre-movement peak (pre-MP), 57 ms before EMG onset, and a post-movement peak (post-MP), 93 ms after EMG onset. From timing information and topographic mapping results, we propose that the pre-MP is largely generated by a tangential source in the anterior bank of the central sulcus and reflects precentral motor processing, whereas the post-MP is generated in the posterior bank of the central sulcus and represents post-central feedback processing. Steady-state MRCPs require actual recording times of less than 10 min, and show excellent inter-session reproducibility. These characteristics may make them convenient for studying sensorimotor cortex activity experimentally and clinically.

Adult

Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters.

Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided.

Adult

Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences.

We used high-frequency repetitive transcranial magnetic stimulation (rTMS) to study the role of the mesial frontocentral cortex (including the supplementary motor area) in the organization of sequential finger movements of different complexity in humans. In 15 subjects, rTMS was randomly applied to the scalp overlying the region of the supplementary motor area and over other positions, including the contralateral primary motor cortex (hand area) during the performance of three overlearned finger sequences on an electronic piano. In all trials, rTMS (frequency 15-20 Hz) started 2 s after the first key press and lasted for approximately 2 s. All sequences were metronome-paced at 2 Hz and retrieved from memory. The 'simple' sequence consisted of 16 repeated index finger key presses, the 'scale' sequence of four times four sequential key presses of the little, ring, middle and index fingers, and the 'complex' sequence of a much less systematic and, therefore, more difficult series of 16 key presses. To measure the effects of rTMS interference with regional cortical function, we analysed rTMS-induced accuracy errors in the movement sequences. Stimulation over the supplementary motor area induced accuracy errors only in the complex sequence, while stimulation over the primary motor cortex induced errors in both the complex and scale sequences, and stimulation over other positions (e.g. F3, F4, FCz, P3, P4) did not interfere with sequence performance at all. Stimulation over the supplementary motor area interfered with the organization of subsequent elements in the complex sequence of movements, with error induction occurring approximately 1 s later than with stimulation over the primary motor cortex. Our findings are in keeping with recent results in non-human primates (Tanji J, Shima K. Nature, 1994; 371: 413-6) indicating a critical role of the supplementary motor area in the organization of forthcoming movements in complex motor sequences that are rehearsed from memory and fit into a precise timing plan.

Adult