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Biomedical subjects

L G Cohen

Publications and source records attributed to L G Cohen.

At least 19 recordsLinked to original sources
PubMed2001

Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain.

Phantom limb pain (PLP) in amputees is associated with reorganizational changes in the somatosensory system. To investigate the relationship between somatosensory and motor reorganization and phantom limb pain, we used focal transcranial magnetic stimulation (TMS) of the motor cortex and neuroelectric source imaging of the somatosensory cortex (SI) in patients with and without phantom limb pain. For transcranial magnetic stimulation, recordings were made bilaterally from the biceps brachii, zygomaticus, and depressor labii inferioris muscles. Neuroelectric source imaging of the EEG was obtained after somatosensory stimulation of the skin overlying face and hand. Patients with phantom limb pain had larger motor-evoked potentials from the biceps brachii, and the map of outputs was larger for muscles on the amputated side compared with the intact side. The optimal scalp positions for stimulation of the zygomaticus and depressor labii inferioris muscles were displaced significantly more medially (toward the missing hand representation) in patients with phantom limb pain only. Neuroelectric source imaging revealed a similar medial displacement of the dipole center for face stimulation in patients with phantom limb pain. There was a high correlation between the magnitude of the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortex and phantom limb pain. These results show enhanced plasticity in both the motor and somatosensory domains in amputees with phantom limb pain.

Adult↗
PubMed2001

Enhancing analogic reasoning with rTMS over the left prefrontal cortex.

The authors utilized repetitive transcranial magnetic stimulation (rTMS) in 16 normal volunteers to investigate the role of the left dorsolateral prefrontal cortex (PFC) in analogic reasoning. rTMS over the left and right PFC, over the left motor cortex, and sham stimulation over the left PFC were administered during memory and analogic reasoning conditions. rTMS over the left PFC led to a significant reduction in response times only in the analogy condition without affecting accuracy. These results indicate that the left PFC is relevant for analogic reasoning and that rTMS applied to the PFC can speed up solution time.

Adult↗
PubMed2001

Mechanisms underlying human motor system plasticity.

There has been increased interest in the ability of the adult human nervous system to reorganize and adapt to environmental changes throughout life. This ability has been termed "plasticity." Plastic changes in the cerebral cortex have been studied: (a) as modifications of sensory or motor cortical representation of specific body parts (cortical maps, body representation level); and (b) as changes in the efficacy of existing synapses or generation of new synapses (neuronal or synaptic level). In this review, we describe paradigms used to study mechanisms of plasticity in the intact human motor system, the functional relevance of such plasticity, and possible ways to modulate it.

Animals↗
PubMed2001

Transcranial magnetic stimulation in the rat.

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7+/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS, 1 and MEPTMS, 2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS, 2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS, 1 followed a sigmoid course, no supramaximal response was reached for MEPTMS, 2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.29+/-0.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS.

Anesthetics↗
PubMed2001

Mechanisms influencing stimulus-response properties of the human corticospinal system.

BACKGROUND: Stimulus-response (S-R) properties of the corticospinal system in humans depend on the interactions that take place at different sites along the corticospinal pathway. The mechanisms influencing stimulus-response curves elicited by transcranial magnetic stimulation (TMS) and their operation site along the human neuraxis are poorly understood. In this study, we investigated the effects of CNS-active drugs with distinct mechanisms of action on S-R curves. Effects of each of these drugs on S-R curves would point to the involvement of specific mechanisms. Additionally, relative sensitivity of S-R curves compared with other measures of corticospinal excitability was studied. METHODS: We studied the effects of lorazepam, which is a positive allosteric modulator of GABA(A) receptors; lamotrigine, an inhibitor of voltage-gated Na(+) and Ca(2+) channels; and D-amphetamine, an indirect agonist of the dopaminergic-adrenergic system on S-R curves, motor thresholds (MT), and intracortical inhibition (ICI) and facilitation (ICF) with a double-pulse technique. Maximum peripheral M responses and F waves were investigated as measures of the total alpha-motoneuron pool and its excitability. RESULTS: F and M waves were unaffected by either the drugs or placebo. S-R curves were significantly depressed by lorazepam and lamotrigine without changes in ICI and ICF. Both S-R curves and ICF were enhanced by D-amphetamine. MT increased only with lamotrigine. CONCLUSIONS: S-R curves were influenced by changes in the GABAergic and monoaminergic system and Na(+) and Ca(2+) channel properties. Our results indicate that, out of different parameters of motor system excitability, S-R curves were the most sensitive.

Adult↗
PubMed2001

Modulation of practice-dependent plasticity in human motor cortex.

Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients.

Adult↗
PubMed2001

Time course of determination of movement direction in the reaction time task in humans.

The primary motor cortex produces motor commands that include encoding the direction of movement. Excitability of the motor cortex in the reaction time (RT) task can be assessed using transcranial magnetic stimulation (TMS). To elucidate the timing of the increase in cortical excitability and of the determination of movement direction before movement onset, we asked six right-handed, healthy subjects to either abduct or extend their right thumb after a go-signal indicated the appropriate direction. Between the go-signal and movement onset, single TMS pulses were delivered to the contralateral motor cortex. We recorded the direction of the TMS-induced thumb movement and the amplitude of motor-evoked potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the end of the reaction time, preceded facilitation of MEPs from the nonprime mover, and both preceded measurable directional change. Compared with a control condition in which no voluntary movement was required, the direction of the TMS-induced thumb movement started to change in the direction of the intended movement as early as 90 ms before the end of the RT, and maximum changes were seen shortly before the end of reaction time. Movement acceleration also increased with maxima shortly before the end of the RT. We conclude that in concentric movements a change of the movement direction encoded in the primary motor cortex occurs in the 200 ms prior to movement onset, which is as early as increased excitability itself can be detected.

Adult↗
PubMed2000

A window into the role of inhibitory and excitatory mechanisms of perception?

The last few years have seen important advances in the better understanding of human cortical physiology. Functional neuroimaging and transcranial magnetic stimulation (TMS) have allowed us to address novel questions and shed different and complementary information on human brain function. In particular, TMS, a non-invasive and virtually painless tool for delivering currents in the brain, has enhanced our understanding of perceptual and motor functions in intact humans. At the same time it has also yielded data on phenomenology, mechanisms, and strategies to modulate these plastic changes in health and disease. Studies using a paired-pulse protocol (Kujirai et al. 1993) allowed detailed investigations of intracortical excitatory and inhibitory interactions in the human motor cortex. This protocol studied the effects of a TMS pulse, delivered at a subthreshold intensity to elicit a motor evoked potential (MEP), on the MEP response to an upcoming suprathreshold TMS pulse. Depending on the interval, the effect of this conditioning pulse may be inhibitory (intracortical inhibition) or excitatory (intracortical facilitation). Abnormalities in these interactions have been described in Parkinson's disease and dystonia (Ridding et al. 1995); differences with control measures have also been described as a function of motor training or learning (Liepert et al. 1998). This protocol has allowed investigators to study mechanisms of both disease and cortical reorganization, for example after amputations (Chen et al. 1998) or motor training processes.

Humans↗
PubMed2000

Enhancing the quality of studies using transcranial magnetic and electrical stimulation with a new computer-controlled system.

Transcranial magnetic (TMS) and electrical (TES) stimulation of the human brain have become useful tools in neurophysiological and neuropsychological research. Here we describe an integrated system that allows experimental control, data recording and analysis of neurophysiological and neuropsychological TMS and TES procedures (including motor thresholds, recruitment curves, intracortical inhibition and facilitation with paired pulses). The system uses a multifunction input/output board and a set of virtual instruments (VI) programmed with the Labview graphical programming language. It also includes online curve fitting of recruitment curves using the Boltzmann sigmoid function and monitoring of the preinnervation grade of the target muscle. Modules for neuropsychological stimulus presentation or faster repetitive stimulation can be easily added. This system yields more accurate data recording and analysis in a user friendly and unified environment.

Computers↗
PubMed2000

Reduction of human visual cortex excitability using 1-Hz transcranial magnetic stimulation.

The effects of low-frequency (1-Hz) repetitive transcranial magnetic stimulation on visual cortex excitability were investigated by measuring phosphene thresholds (PTs) and stimulus-response curves. Stimulation over the visual cortex led to significantly decreased visual cortex excitability, expressed as an increase in PT. The motor threshold of the hand muscles did not change, indicating the topographic specificity of this effect. This intervention may be useful in situations associated with a hyperexcitable visual cortex.

Adult↗
PubMed2000

A positron emission tomographic study of auditory localization in the congenitally blind.

We have used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in sighted and congenitally blind subjects performing auditory localization tasks. During scanning, the spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During tasks that required auditory localization both the sighted and blind subjects strongly activated posterior parietal areas. In addition, the blind subjects activated association areas in the right occipital cortex, the foci of which were similar to areas previously identified in visual location and motion detection experiments in sighted subjects. The blind subjects, therefore, demonstrated visual to auditory cross-modal plasticity with auditory localization activating occipital association areas originally intended for dorsal-stream visual processing. To determine the functional connectivity of pre-selected brain regions in primary and non-primary auditory and posterior parietal cortex in the two cohorts, we performed an inter-regional correlation analysis on the rCBF data set. During auditory localization in the blind subjects, rCBF activity in the right posterior parietal cortex was positively correlated with that in the right occipital region, whereas in sighted subjects correlations were generally negative. There were no significant positive occipital correlations in either cohort when reference regions in temporal or left parietal cortex were chosen. This indicates that in congenitally blind subjects the right occipital cortex participates in a functional network for auditory localization and that occipital activity is more likely to arise from connections with posterior parietal cortex.

Adult↗
PubMed2000

Mechanisms of use-dependent plasticity in the human motor cortex.

Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-d-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-d-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation.

Dextromethorphan↗
PubMed2000

Reproducibility of intracortical inhibition and facilitation using the paired-pulse paradigm.

We have evaluated the reproducibility of intracortical inhibition (ICI) and facilitation (ICF) studied with paired-pulse focal transcranial magnetic stimulation. Three investigators studied the same subjects (n = 4) in three different sessions. A high variability was shown across subjects [coefficient of variation, (cv) 67.3% for ICI and 21.2% for ICF]. Intersession variability was up to 37.1% for ICI and 22.7% for ICF. Interinvestigator variability was 17.3% for ICI and negligible for ICF. Our results may have implications for planning future studies.

Adult↗
PubMed2000

Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent.

Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25-30 ms and 150-200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homotopic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150- to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus. Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved.

Adult↗
PubMed2000

Voluntary teeth clenching facilitates human motor system excitability.

OBJECTIVE: Voluntary contraction of the teeth is a common maneuver used to facilitate peripheral monosynaptic reflexes. It was the aim of this study to determine the site along the neuraxis where this effect occurs. METHODS: Focal transcranial magnetic stimulation (TMS) was used to measure recruitment curves, motor thresholds and intracortical inhibition and facilitation from the right first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in seven normal volunteers. Changes in excitability in subcortical structures during teeth clenching were studied using F waves, H reflexes, and brainstem magnetic stimulation. RESULTS: Recruitment curves of FDI and TA showed significant facilitation during voluntary teeth clenching indicating an overall enhancement in the motor system excitability. Teeth clenching additionally resulted in decreased intracortical inhibition in the FDI but not in TA, pointing to an intracortical site of enhancement for the hand. Motor evoked potentials (MEPs) following stimulation at the brainstem level and F waves in FDI and soleus H reflex amplitude were also facilitated by teeth clenching, indicating a subcortical site for this effect for the upper and lower extremity. M wave amplitudes did not change. CONCLUSIONS: The teeth clenching maneuver had a similar facilitatory effect on upper and lower extremities. Cortical and subcortical sites contribute to this effect in a hand muscle while only subcortical sites were identified in this facilitatory effect on the lower extremity.

Adult↗
PubMed2000

Motor cortex excitability in patients with cerebellar degeneration.

OBJECTIVES: To study motor cortex (M1) excitability and the effect of subthreshold transcranial magnetic stimulation (TMS) in patients with cerebellar degeneration and normals performing a reaction time (RT) task. METHODS: Time to wrist flexion after a visual go-signal was measured. TMS was always delivered at 90% of resting motor evoked potential (MEP) threshold. In one experiment, test TMS was delivered at various intervals after the go-signal. In half the trials priming TMS was also given with the go-signal. A second experiment examined the effect on RT of M1 and occipital priming stimulation alone. RESULTS: M1 excitability, measured as the likelihood of producing MEPs in the wrist flexor muscles, increased immediately after the go-signal in the patients and stayed high until movement. In controls, excitability rose gradually. This difference was largely eliminated by priming TMS. RT was longer in the patient group, but improved with priming TMS. Occipital priming produced less effect on RT than M1 stimulation in both controls (P=0.008) and patients (P=0.0004). CONCLUSIONS: M1 excitability prior to movement in an RT task increases abnormally early in cerebellar patients. This may reflect compensation for deficient thalamocortical drive. Subthreshold TMS can partially normalize the prolonged RT and abnormal excitability rise in cerebellar patients.

Adult↗
PubMed2000

Induction of plasticity in the human motor cortex by paired associative stimulation.

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.

Adult↗