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Influence of internal globus pallidus stimulation on motor cortex activation pattern in Parkinson's disease.

OBJECTIVES: Indications of the functional neurosurgical treatments become more and more numerous, however, few methods were used to study the mechanism of action and some discrepancies came to light. We assessed the influence of internal globus pallidus (GPI) stimulation and L-Dopa on cortical activation during the preparation and execution phases of the movement compared to clinical improvement of Parkinson's disease. METHODS: We recorded the movement-related cortical potential and movement-related desynchronization. RESULTS: The Unified Parkinson's Disease Rating Scale was improved by 46% under stimulation and 64% under stimulation with L-Dopa. Premovement desynchronization was significantly increased on central contralateral derivation under stimulation with L-Dopa and decreased on frontocentral ipsilateral derivation under stimulation with and without L-Dopa. Movement desynchronization was improved on the contralateral motor cortex under stimulation with and without L-Dopa (benefit correlated with bradykinesia improvement). The movement-related postmotor potential was significantly increased under stimulation with L-Dopa. CONCLUSIONS: GPI stimulation alone influenced the premotor cortex activation during the planning and induced a selective and focal effect on the organisation of motor cortical activity during the movement execution which may explain bradykinesia improvement. The motor cortex activation improvement under stimulation with L-Dopa concerned both the movement preparation and execution but remained very localised to the contralateral motor cortex.

Aged↗

Volumetric image guidance for motor cortex stimulation: integration of three-dimensional cortical anatomy and functional imaging.

OBJECTIVE: Epidural electrical stimulation of the motor cortex is a promising treatment option in patients with intractable pain. Varying rates of success in long-term pain relief have been attributed to inaccurate positioning of the electrode array, partly because the sulcal landmarks are not directly visualized. We describe an integrated protocol for precise electrode placement, combining functional image guidance and intraoperative electrical stimulation in the awake patient. METHODS: Volumetric rendering of a three-dimensional (3-D) magnetic resonance data set was used to visualize the cortical surface and to superimpose functional magnetic resonance imaging data in six patients with refractory chronic pain. The intraoperative positioning of the quadripolar electrode array was monitored by functional 3-D image guidance. Continuous electrophysiological monitoring and clinical assessment of the motor effects complemented the procedure. RESULTS: Volumetrically rendered 3-D images were advantageous for the location of the burr hole over the perirolandic area by revealing individual cortical morphological features (e.g., the hand knob) and function at the same time. The exact position of the electrodes was verified reliably by cortical stimulation. No complications were observed throughout the procedures. CONCLUSION: The combination of 3-D functional neuronavigation, intraoperative electrical stimulation, and continuous motor output monitoring in awake patients provides optimal information for the identification of the appropriate somatotopic area of motor cortex. This combined imaging and stimulation approach for electrode positioning offers a safe and minimal invasive strategy for the treatment of intractable chronic pain in selected patients.

Adult↗

Natural rhythm: evidence for occult 40 Hz gamma oscillation in resting motor cortex.

Fast gamma oscillations, often at 40 Hz, have been demonstrated throughout the brain including the thalamus, auditory, visual and motor cortices. The function of gamma rhythms is elusive, but several authors have hypothesized that they contribute to the "binding" of diverse information into a single coherent percept, and to the synchronization of movement. In skeletal muscle a "Piper rhythm" around 40 Hz is commonly observed during maximal voluntary contraction, and has been shown to correlate with activity of similar frequency in a limited area of contralateral motor cortex. Gamma rhythms are detected primarily during complex cortical activity, and are seldom recorded at rest or coherently over wide areas. Here we use bihemispheric transcranial magnetic stimulation (TMS) to study time-dependent correlations between evoked motor potentials from non-homologous muscles in opposite limbs of normal volunteers. The results suggest the presence of an occult, synchronous 40 Hz rhythm across broad areas of resting motor cortex in both hemispheres.

Biological Clocks↗

Epidural electrical stimulation of the motor cortex in patients with facial neuralgia.

Chronic facial neuralgias often do not respond sufficiently to standard treatment methods. Alternative modalities are needed for long-term reduction of pain in such cases. The present preliminary report describes two patients with trigeminal and glossopharyngeal neuralgia, respectively, treated with standard methods without obtaining satisfactory pain relief. Electrical stimulation of the motor cortex contralateral to the pain area was employed in both cases and proved able to produce a long-term facial pain reduction. Alleviation of pain occurred after activation of the flat quadripolar electrode placed epidurally on the precentral cortical area and lasted as long as the stimulator was working. By changing the polarity of the electrodes, it was possible to induce tingling sensations and muscle activation not only contralaterally to the stimulated motor cortex, but also in the ipsilateral part of the face. No stimulator-independent pain reduction resulted from long-term use of the stimulation device. During a follow-up period of 18 months, a sufficient and relatively stable analgesic effect of electrostimulation was observed. One major complication of motor cortex stimulation during the follow-up period was a single generalized epileptic seizure in one of the patients.

Adult↗

Ipsilateral motor cortex activity during unimanual hand movements relates to task complexity.

Functional imaging studies have revealed recruitment of ipsilateral motor areas during the production of sequential unimanual finger movements. This phenomenon is more prominent in the left hemisphere during left-hand movements than in the right hemisphere during right-hand movements. Here we investigate whether this lateralization pattern is related specifically to the sequential structure of the unimanual action or generalizes to other complex movements. Using event-related fMRI, we measured activation changes in the motor cortex during three types of unimanual movements: repetitions of a sequence of movements with multiple fingers, repetitive "chords" composed of three simultaneous key presses, and simple repetitive tapping movements with a single finger. During sequence and chord movements, strong ipsilateral activation was observed and was especially pronounced in the left hemisphere during left-hand movements. This pattern was evident for both right-handed and, to a lesser degree, left-handed individuals. Ipsilateral activation was less pronounced in the tapping condition. The site of ipsilateral activation was shifted laterally, ventrally, and anteriorly with respect to that observed during contralateral movements and the time course of activation implied a role in the execution rather than planning of the movement. A control experiment revealed that strong ipsilateral activity in left motor cortex is specific to complex movements and does not depend on the number of required muscles. These findings indicate a prominent role of left hemisphere in the execution of complex movements independent of the sequential nature of the task.

Analysis of Variance↗

Morphological diversity of immunocytochemically identified GABA neurons in the monkey sensory-motor cortex.

GABAergic neurons have been identified in monkey sensory-motor cerebral cortex by light microscopic, immunocytochemical localization of the GABA synthesizing enzyme, glutamic acid decarboxylase (GAD). All GAD-positive neurons are non-pyramidal cells. Their somata are present in all layers and are evenly distributed across layers II-VI of the motor cortex (area 4), but are found in greater concentrations in layers II, IV and VI of all areas of first somatic sensory cortex (SI; areas 3a, 3b and 1-2). GAD-positive puncta (putative axon terminals) are present throughout the sensory-motor cortex, and they are found immediately adjacent to the somata, dendrites and presumptive axon initial segments of GAD-negative pyramidal cells. In addition, they are observed in close approximation to the somata of both large and small GAD-positive neurons. In area 4, the density of puncta is highest in the superficial cortical layers (layers I-III) and gradually declines throughout the deeper layers. In SI, the highest densities of puncta are present in layer IV, while moderately high densities are found in layers I-III and VI. In areas 3a and 3b, the puncta in layers IV and VI are particularly numerous and form foci that exhibit greater density than adjacent regions. GAD-positive neurons with large somata, 15-33 micron in diameter, are present in layers IIIB-VI of all areas. Such cells have many primary dendrites that radiate in all directions. In addition they have axons that ascend either from the superficial aspect of the somata or from primary dendrites, and that exhibit horizontal collateral branches. These neurons closely resemble the large basket cells (Marin-Padilla, 1969; Jones, 1975), and they may give rise to many of the GAD-positive endings surrounding the somata and proximal dendrites of pyramidal cells in layers III-VI. In addition, small GAD-positive somata are present in all layers, but they are most numerous in layers II and IIIA of all areas and in layer IV of SI. The somata and proximal dendrites of these cells vary from a multipolar shape with small, beaded dendrites, found primarily in layer IV, to bitufted and multipolar shapes with larger, smooth dendrites. The diversity of somal sizes and locations, the variety of dendritic patterns, and the different distributions of GAD-positive puncta, all combine to suggest that several different morphological classes of intrinsic neurons comprise the GABA neurons of monkey cerebral cortex.

Animals↗

[Activity of anterolateral motor cortex neurons in instumental food-acquisition and alcohol-acquisition behavior].

Singleunit activity of anterolateral area of motor cortex in rabbits subjected to chronic ethanol treatment was recorded to study interconnections of neuronal mechanisms of newly formed instrumental alcohol-acquisition behavior (IAB) and previously formed food-acquisition behavior (IFB). Adult animals were trained to perform IFB in experimental cage equipped with two food boxes and two pedals situated in the corners of the cage. Food was presented automatically in a food box after the pressing of an appropriate pedal. Same rabbits after 9 mo. of chronic alcohol treatment were trained to perform IAB in the same experimental cage (gelatin capsules filled with 15% ethanol solution were placed into the food box instead of food). Activity of 121 units of anterolateral area of motor cortex was studied. Each unit discharges were analysed in IAB as well as in IFB. The data obtained testifies that neuronal sets subserving IAB and IFB overlap but not completely. 44 "common" neurons permanently activated in both behaviors and 3 neurons specifically activated in each of behaviors (one in IAB and two in IFB) were found. We consider the formation of IAB as systemogenesis that is related to the consolidation processes: the formation of new neuronal specializations and to the accommodative re-consolidation: modification of early specialized cells ("common"). It is shown in the Discussion that present experiments help us not only understand interconnections of neuronal mechanisms of newly formed IAB and early formed IFB but also provide an additional insight into the nature of similarity between neuronal mechanisms of long-term memory and long-lived modifications resulting from repeated drug exposure.

Animals↗

The neural response to transcranial magnetic stimulation of the human motor cortex. II. Thalamocortical contributions.

Beta oscillations (15-30 Hz) constitute an important electrophysiological signal recorded in the resting state over the human precentral gyrus. The brain circuitry involved in generating the beta oscillations is not well understood but appears to involve both cortical and subcortical structures. We have shown that single pulses of transcranial magnetic stimulation (TMS) applied over the primary motor cortex consistently elicit a brief beta oscillation. Reducing the local cortical excitability using low-frequency repetitive TMS does not change the amplitude of the induced beta oscillation (Van Der Werf and Paus in Exp Brain Res DOI 10.1007/s00221-006-0551-2). Here, we investigated the possible involvement of the thalamus in the cortically expressed beta response to single-pulse TMS. We included eight patients with Parkinson's disease who had undergone unilateral surgical lesioning of the ventrolateral nucleus of the thalamus. We administered 50 single pulses of TMS, at an intensity of 120% of resting motor threshold, over the left and right primary motor cortex and, at the same time, recorded the electroencephalogram (EEG) using a 60-electrode cap. We were able to perform analyses on seven EEG data sets and found that stimulation of the unoperated hemisphere (with thalamus) resulted in higher amplitudes of the single-trial induced beta oscillations than in the operated hemisphere (with thalamotomy). The beta oscillation obtained in response to pulses applied over the unoperated hemisphere was also higher than that obtained in healthy controls. We suggest that (1) the beta oscillatory response to pulses of TMS applied over the primary motor cortex is higher in Parkinson's disease patients, (2) thalamotomy serves to reduce the abnormally high TMS-induced beta oscillations, and (3) the motor thalamus facilitates the cortically generated oscillation, through cortico-subcortico-cortical feedback loops.

Aged↗

A FAIR study of motor cortex activation under normo- and hypercapnia induced by breath challenge.

In this study an arterial spin-tagging technique based on flow-sensitive alternating inversion recovery (FAIR) with single-shot spiral data acquisition was used to study how the basal cerebral blood flow (CBF) elevated by breath holding affects the regional cerebral blood flow (rCBF) response to focal brain activation in the motor cortex. Six subjects were examined using three types of activation studies. These were (a) bilateral finger tapping paced at 4 Hz under normal breathing, (b) repeated expiration breath holding of 30 s, and (c) simultaneous breath holding and finger tapping. It was found that in five of six subjects the prevailing CBF level adjusted by breath challenge and the increase in rCBF in motor cortex associated with bilateral finger tapping were completely additive. This finding from FAIR-based functional magnetic resonance imaging is in accordance with that reported from published positron emission tomography studies. The results indicate that in the majority of the subjects examined the regulatory mechanisms for vasodilatory reaction to CO(2) and rCBF response to neural activation in motor cortex region are independent.

Adult↗

Functional relations between primate motor cortex cells and muscles: fixed and flexible.

In behaving monkeys the effects of motor cortex cells on muscles are inferred from two quite different types of 'correlational' evidence: their coactivation and cross-correlation. Many precentral cells are coactivated with limb muscles, suggesting that they make a proportional contribution to muscle activity; however, such coactivation is typically quite flexible, and can be changed by operantly conditioning the dissociation of cell and muscle activity. Cross-correlating cells and muscles by spike-triggered averaging of the electromyogram (EMG) shows that certain cells produce short-latency post-spike facilitation of EMG; this correlational linkage is relatively fixed under different behavioural conditions and its time course suggests it is mediated by a corticomotoneuronal (CM) synaptic connection. CM cells typically facilitate a set of coactivated agonist muscles, and some also inhibit their antagonists. The firing patterns of CM cells can differ significantly from those of their target muscles. During ramp-and-hold wrist responses most CM cells discharge a phasic burst that precedes target muscle onset and that contributes to changes in muscle activity. At low force levels many CM cells are activated without their target motor units. Conversely, many CM cells are paradoxically inactive during rapid forceful movements that vigorously activate their target muscles; they appear to be preferentially active during finely controlled movements. Thus CM cells, with a fixed correlational linkage to their target muscles, may be recruited without their target muscles, and vice versa.

Animals↗

Afferent conditioning of motor evoked potentials following transcranial magnetic stimulation of motor cortex in normal subjects.

The present study determined the effects of percutaneous electrical stimulation of the plantar surface on motor evoked potentials (MEPs) in tibialis anterior (TA) and soleus (SOL) of normal subjects following transcranial magnetic stimulation of motor cortex. The conditioning stimulation consisted of a 20 msec train of electrical pulses (500 Hz; 0.1 msec rectangular) delivered to the medial border of the sole of the foot at an intensity just subthreshold for evoking a flexion reflex. The conditioning (C) stimulation preceded the test (T) cortical stimulation by intervals of 20-130 msec. Magnetic stimulation of motor cortex (Cadwell MES-10) was delivered through a 9.5 cm focal point coil positioned tangential to the scalp and located with the rim over vertex. Five healthy adults served as subjects and each was investigated on at least 2 occasions. At C-T intervals 20-50 msec there was a mild inhibition of MEPs in both TA and SOL. This was followed by marked facilitation (greater than 300%) of MEPs at C-T intervals 50-85 msec in both TA and SOL in all subjects. At longer C-T intervals greater than 110 msec, there was an inhibition of MEPs in TA but not in SOL. Based on the time course of these 3 phases of MEP amplitude modulation, and different stimulation thresholds for each phase, it appears that separate neurophysiological processes underlie each phase of MEP modulation. These observations also suggest that percutaneous electrical stimulation may be useful as a means of enhancing low amplitude or subliminal MEPs in normal subjects or patients with myelopathy.

Adaptation, Physiological↗

Contrasting properties of motor output from the supplementary motor area and primary motor cortex in rhesus macaques.

The goal of this study was to assess the motor output capabilities of the forelimb representation of the supplementary motor area (SMA) in terms of the sign, latency and strength of effects on electromyographic (EMG) activity. Stimulus triggered averages of EMG activity from 24 muscles of the forelimb were computed in SMA during a reach-to-grasp task. Poststimulus facilitation (PStF) from SMA had two distinct peaks (15.2 and 55.2 ms) and one poststimulus suppression (PStS) peak (32.4 ms). The short onset latency PStF and PStS of SMA were 5.5 and 16.8 ms longer than those of the primary motor cortex (M1). The average magnitudes (peak increase or decrease above baseline) of the short and long latency PStF and PStS from SMA at 60 microA were 13.8, 11.3 and -11.9% respectively. In comparison, M1 PStF and PStS magnitudes at 15 microA were 50.2 and -23.8%. Extrapolating M1 PStF magnitude to 60 microA yields a mean effect that is nearly 15 times greater than the mean PStF from SMA. Moreover, unlike M1, the facilitation of distal muscles from SMA was not significantly greater than the facilitation of proximal muscles. We conclude that the output from SMA to motoneurons is markedly weaker compared with M1 raising doubts about the role of SMA corticospinal neurons in the direct control of muscle activity.

Animals↗

Increased regional cerebral blood flow in the contralateral thalamus after successful motor cortex stimulation in a patient with poststroke pain.

The mechanisms underlying poststroke pain have not been clearly identified. Although motor cortex stimulation (MCS) sometimes reduces poststroke pain successfully, the exact mechanism is not yet known. For further investigation of the neural pathways involved in the processing of poststroke pain and in pain reduction by MCS, the authors used positron emission tomography (PET) scanning to determine significant changes in regional cerebral blood flow (rCBF). This 58-year-old right-handed man suffered from right-sided poststroke pain for which he underwent implantation of a stimulation electrode in the right motor cortex. After 30 minutes of stimulation, his pain was remarkably reduced (Visual Analog Scale scores decreased 8 to 1) and he felt warmth in his left arm. The rCBF was studied using PET scanning with 15O-labeled water when the patient was in the following states: before MCS (painful condition, no stimulation) and after successful MCS (painless condition, no stimulation). The images were analyzed using statistical parametric mapping software. State-dependent differences in global blood flow were covaried using analysis of covariance. Comparisons of the patient's rCBF in the painful condition with that in the painless condition revealed significant rCBF increases in the left rectus gyrus (BA11), left superior frontal lobe (BA9), left anterior cingulate gyms (BA32), and the left thalamus (p < 0.05, corrected). On the other hand, there were significant decreases in rCBF in the right superior temporal gyrus (BA22, p < 0.01, corrected) and the left middle occipital gyrus (BA19, p < 0.05, corrected). The efficacy of MCS was mainly related to increased synaptic activity in the thalamus, whereas the activations in the rectus gyrus, anterior cingulate gyrus, and superior frontal cortex as well as the inactivation of the superior temporal lobe may be related to emotional processes. This is the first report in which the contralateral thalamus was significantly activated and pain relief was achieved using MCS.

Cerebral Hemorrhage↗

Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis. Evidence from paired transcranial magnetic stimulation.

We investigated 14 patients with amyotrophic lateral sclerosis (ALS) by paired conditioning-test transcranial magnetic stimulation to test the hypothesis that the motor cortex is hyperexcitable in ALS. Intracortical (corticocortical) inhibition was significantly less in the ALS group than in an age-matched healthy control group (85.3 +/- 27.0% versus 45.2 +/- 15.5%, respectively; p < 0.0001). In contrast, intracortical facilitation, motor threshold, and cortical silent period duration in the ALS patients were not different from the control group. We suggest that the selective abnormality of intracortical inhibition is best compatible with an impaired function of inhibitory interneuronal circuits in the motor cortex that in turn renders the corticomotoneuron hyperexcitable.

Aged↗

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Adult↗

Commissural columns in the sensory-motor cortex of monkeys.

Callosally projecting cells and the terminal ramifications of their axons were identified in the monkey sensory-motor cortex by retrograde and anterograde labeling techniques, often by double labeling cells and axons in the same animal. Bundles of callosal fibers terminate in small column-like zones 0.5-1 mm wide in the motor cortex (area 4) and in the first (SI) and second (SII) somatic sensory areas. Such columns are aligned in register to form elongated strips extending mediolaterally in the long axes of the pre- and postcentral gyri. Significant portions of area 4, SI and SII, in regions corresponding to the representations of the hand and foot, are not callosally connected. The cells of origin of callosal fibers in SI are largely confined to layer IIIB and form columns and strips corresponding to the above. In connected zones of SI, the callosal connection is reciprocal and precisely point-to point. This and the laminar distribution of the terminal ramifications of callosal fibers (to layers I-IV) suggest that callosal fibers may arise from the terminate upon exactly homotopic, column-like groups of layer IIIB pyramidal cells. Commissurally projecting cells and their terminal ramifications are not limited to particular architectonic fields or particular parts of fields in SI. All architectonic fields of SI project heterotopically to the contralateral SII.

Animals↗

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

OBJECT: The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. METHODS: The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image and the image data set was implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyri were identified by neuronavigation and, in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the procedure. CONCLUSIONS: The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to lessen morbidity around eloquent brain areas.

Adolescent↗

On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional static isometric force.

We examined the relations between the steady-state frequency of discharge of cells in the arm area of the motor cortex of the monkey and the direction and magnitude of the three-dimensional static force exerted by the arm on an isometric manipulandum. Data were analyzed from two monkeys (n = 188 cells) using stepwise multiple linear regression. In 154 of 188 (81.9%) cells the regression model was statistically significant (P < 0.05). In 121 of 154 (78.6%) cells the direction but not the magnitude of force had a statistically significant effect on cell activity; in 11 of 154 (7.1%) cells only the magnitude effect was significant; and in 22 of 154 (14.3%) cells both the direction and magnitude effects were significant. The same analysis was used to assess the effect of the direction and magnitude of force on the electromyographic activity of 9 muscles of the arm and shoulder girdle. The regression model was statistically significant. For all the muscles studied in 4 of 9 (44.4%) muscles only the direction effect was significant whereas in the remaining 5 of 9 (55.6%) muscles both the direction and the magnitude were significant. No muscle studied showed a significant effect of force magnitude alone. These differences in the frequency of occurrence of directional and magnitude effects between cells and muscles were statistically significant (P < 0.005, chi 2 test). These findings underscore the fundamental importance of the direction of force in space for both motor cortical cells and proximal muscles and underline the differential relations of the cells and muscles to the direction and magnitude of force. These results indicate that the specification of the magnitude of three-dimensional force is embedded within the directional signal; this combined direction+magnitude effect was 3.9 times more prevalent in the muscles than in the cells studied. In contrast, the pure directional effect was 1.8 times more prevalent in the cells than in the muscles studied. This suggests that the direction of force can be controlled independently of its magnitude and that this direction signal is especially prominent in the motor cortex.

Animals↗