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L G Cohen

Publications and source records attributed to L G Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Levodopa increases memory encoding and dopamine release in the striatum in the elderly.

Normal aging is associated with a decrease in dopaminergic function and a reduced ability to form new motor memories with training. This study examined the link between both phenomena. We hypothesized that levodopa would (a) ameliorate aging-dependent deficits in motor memory formation, and (b) increase dopamine availability at the dopamine type 2-like (D2) receptor during training in task-relevant brain structures. The effects of training plus levodopa (100mg, plus 25mg carbidopa) on motor memory formation and striatal dopamine availability were measured with [(11)C]raclopride (RAC) positron emission tomography (PET). We found that levodopa did not alter RAC-binding potential at rest but it enhanced training effects on motor memory formation as well as dopamine release in the dorsal caudate nucleus. Motor memory formation during training correlated with the increase of dopamine release in the caudate nucleus. These results demonstrate that levodopa may ameliorate dopamine deficiencies in the elderly by replenishing dopaminergic presynaptic stores, actively engaged in phasic dopamine release during motor training.

Aged↗
PubMed2006

Contribution of noninvasive cortical stimulation to the study of memory functions.

In the memory domain, a large body of experimental evidence about subsystems of memory has been collected from classic lesion studies and functional brain imaging. Animal studies have provided information on molecular mechanisms of memory formation. Compared to this work, transcranial magnetic stimulation and transcranial direct current stimulation have made their own unique contribution. Here, we describe how noninvasive brain stimulation has been used to study the functional contribution of specific cortical areas during a given memory task, how these techniques can be used to assess LTP- and LTD-like plasticity in the living human brain, and how they can be employed to modulate memory formation in humans, suggesting an adjuvant role in neurorehabilitative treatments following brain injury.

Animals↗
PubMed2006

Neuroimaging patterns associated with motor control in traumatic brain injury.

OBJECTIVE: To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor outcome in the functional maps of these patients? METHODS: In an exploratory cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. RESULTS: Compared to age-matched, healthy controls performing the same task, TBI patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to "poor clinical outcome" had decreased fMRI-signal change in the cSM1 during baseline. CONCLUSIONS: These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.

Adolescent↗
PubMed2005

Dopaminergic effects on encoding of a motor memory in chronic stroke.

The effects of a single oral dose of levodopa administered in a randomized, double-blind, placebo-controlled cross-over design on formation of a motor memory were studied by a training protocol in patients with chronic stroke. Levodopa enhanced the ability of motor training to encode an elementary motor memory relative to placebo. Up-regulation of dopaminergic function may enhance motor memory formation, crucial for successful rehabilitative treatments in patients with chronic stroke.

Aged↗
PubMed2005

Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal.

OBJECTIVE: Previous reports characterized the effects of administration of single oral doses of antiepileptic drugs (AED) on cortical excitability. However, AED effects on cortical excitability, and their relationship to plasma blood levels, during chronic drug administration at therapeutic doses are not known. The objective of the study was to determine whether plasma blood levels during chronic administration at therapeutic doses would accurately predict changes in corticomotor excitability. METHODS: We used transcranial magnetic stimulation (TMS) to measure cortical excitability during 5 weeks administration of carbamazepine (CBZ) and lamotrigine (LTG), and subsequent AED withdrawal in 20 healthy volunteers. Data were analyzed using ANOVA(RM) and regression analysis. RESULTS: Resting motor thresholds (r-MT) increased with increasing total and free CBZ and LTG levels during drug administration, but not drug withdrawal. After acute AED withdrawal, r-MT elevation persisted in most individuals with CBZ despite undetectable plasma levels, compared to a rapid normalization with LTG. In contrast, acute drug withdrawal resulted in a transient decrease in r-MT in 3/10 individuals with CBZ and 2/10 with LTG. CONCLUSIONS: Plasma levels provide information on motor cortical function during active treatment phases but not during AED withdrawal. SIGNIFICANCE: The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures.

Adult↗
PubMed2004

Kinematically specific interhemispheric inhibition operating in the process of generation of a voluntary movement.

Unilateral hand movements are accompanied by a transient decrease in corticospinal (CS) excitability of muscles in the opposite hand. However, the rules that govern this phenomenon are not completely understood. We measured the amplitude of motor evoked potentials (MEP) in the left first dorsal interosseus (FDI) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex in order to assess CS excitability changes that preceded eight possible combinations of unilateral and bilateral index finger movements with different right hand positions. Left FDI MEP amplitude (MEP(Left FDI)) increased when this muscle acted as an agonist and tended to decrease when it was an antagonist. Additionally, MEP(Left FDI) decreased substantially before right index finger abduction (a movement mediated by the right FDI) when both hands were lying flat (a movement mirroring left index finger abduction) but not when the right hand was turned at 90 degrees or flat with the palm up. Therefore, CS excitability of the resting FDI was differentially modulated depending on the direction of the opposite index finger movement, regardless of muscles engaged in the task. These results indicate that inhibitory interactions preceding unilateral finger movements are determined by movement kinematics possibly to counteract the default production of mirror motions.

Adult↗
PubMed2003

Modulation of excitability of human motor cortex (M1) by 1 Hz transcranial magnetic stimulation of the contralateral M1.

OBJECTIVE: Previous studies demonstrated that single-pulse transcranial magnetic stimulation (TMS) of one motor cortex (M1) exerts a brief inhibitory effect on the contralateral M1. The purpose of this study was to test the hypothesis that 30min of 1Hz TMS of M1 will result in a lasting increase in excitability in the contralateral M1. METHODS: Healthy volunteers were tested on 2 separate days, before (baseline) and after one of two interventions: (a) stimulation of M1 with 1Hz TMS for 30min at 115% of resting motor threshold, and (b) sham stimulation. Recruitment curves to TMS, pinch force, and simple reaction time were assessed in the hand contralateral to the unstimulated motor cortex. RESULTS: The main finding of this study was that 30min of 1Hz significantly increased recruitment curves in the contralateral motor cortex in the real stimulation condition relative to sham (P<0.005, factorial analysis of variance (ANOVA)). This change outlasted the stimulation period for at least 15min and occurred in the absence of changes in pinch force or reaction time. CONCLUSIONS: These results raise the potential for inducing lasting modulation of excitability in M1 by 1Hz TMS of the other M1, a phenomenon possibly reflecting modulation of interhemispheric interactions. SIGNIFICANCE: It is conceivable that 1Hz TMS applied to M1 may be used to modulate excitability in the opposite motor cortex for therapeutic purposes.

Aged↗
PubMed2003

Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation.

OBJECTIVE: Comparison of functional magnetic resonance imaging (fMRI) representational maps, that were generated during voluntary thumb abduction, hand dorsiflexion and foot elevation to amplitude maps of motor-evoked potentials (MEPs) elicited by single transcranial magnetic stimulation (TMS) administered to cortical motor representation areas of the muscles of the thenar eminence, extensor carpi radialis and tibialis anterior muscles. METHODS: Stimulus locations that produced maximal motor-evoked potential amplitudes were compared to fMRI activation maxima in three-dimensional (3D)-space and in a 2D-projection using a novel technique that allowed fMRI activation sites to be projected onto the surface of the brain. RESULTS AND CONCLUSIONS: When analyzing pooled data from all target muscles, the location of projected fMRI and TMS activation maxima on the cortical surface differed by an average 13.9 mm. The differences in 3D distances were particularly large for representation areas of lower leg muscles. 3D distances between fMRI activation maxima and highest MEP site in TMS correlated significantly with higher TMS thresholds. These observations strongly suggest that higher TMS excitation thresholds and lower MEP amplitudes are largely due to the absolute distance between the stimulation site and the excitable cortical tissue targeting this muscle. After the projection 4 out of 5 representation sites as evaluated by TMS were located anterior to the fMRI activation maxima, an observation which may due to the orientation of the magnetic field induced by the current in the coil. The representation sites as evaluated with both methods were specific for the type of movement: distances between representation maxima of the same movements were significantly smaller than those within different movements. Nevertheless, fMRI and TMS provide complementary information, which is discussed on the basis of the functional map observed with both methods.

Adult↗
PubMed2002

Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training.

Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter mediating alpha(1)-adrenergic function) and downregulated by alpha(1)-adrenergic antagonists. In spite of this, alpha(1)-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings. The purpose of this study was to determine the effects of a single oral dose of the alpha(1)-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent plasticity relative to a drug-free condition. These data suggest caution when using alpha(1)-adrenergic blockers in rehabilitative clinical settings following brain lesions.

Adrenergic alpha-Antagonists↗
PubMed2002

Enhancement of use-dependent plasticity by D-amphetamine.

In healthy individuals, motor training can elicit use-dependent plasticity. Here the authors studied six subjects in whom training alone failed to elicit this effect. Administration of a single dose of 10 mg of D-amphetamine preceding training led to use-dependent plasticity in a subgroup of these subjects. Using pharmacologic interventions to enhance the effects of motor training might help rehabilitative efforts in patients in whom training alone fails.

Adult↗
PubMed2002

Simulating transcranial magnetic stimulation during PET with a large-scale neural network model of the prefrontal cortex and the visual system.

Transcranial magnetic stimulation (TMS) exerts both excitatory and inhibitory effects on the stimulated neural tissue, although little is known about the neurobiological mechanisms by which it influences neuronal function. TMS has been used in conjunction with PET to examine interregional connectivity of human cerebral cortex. To help understand how TMS affects neuronal function, and how these effects are manifested during functional brain imaging, we simulated the effects of TMS on a large-scale neurobiologically realistic computational model consisting of multiple, interconnected regions that performs a visual delayed-match-to-sample task. The simulated electrical activities in each region of the model are similar to those found in single-cell monkey data, and the simulated integrated summed synaptic activities match regional cerebral blood flow (rCBF) data obtained in human PET studies. In the present simulations, the excitatory and inhibitory effects of TMS on both locally stimulated and distal sites were studied using simulated behavioral measures and simulated PET rCBF results. The application of TMS to either excitatory or inhibitory units of the model, or both, resulted in an increased number of errors in the task performed by the model. In experimental studies, both increases and decreases in rCBF following TMS have been observed. In the model, increasing TMS intensity caused an increase in rCBF when TMS exerted a predominantly excitatory effect, whereas decreased rCBF following TMS occurred if TMS exerted a predominantly inhibitory effect. We also found that regions both directly and indirectly connected to the stimulating site were affected by TMS.

Brain Mapping↗
PubMed2002

Nervous system reorganization following injury.

Contrary to the classical view of a pre-determined wiring pattern, there is considerable evidence that cortical representation of body parts is continuously modulated in response to activity, behavior and skill acquisition. Both animal and human studies showed that following injury of the peripheral nervous system such as nerve injury or amputation, the somatosensory cortex that responded to the deafferented body parts become responsive to neighboring body parts. Similarly, there is expansion of the motor representation of the stump area following amputation. Reorganization of the sensory and motor systems following peripheral injury occurs in multiple levels including the spinal cord, brainstem, thalamus and cortex. In early-blind subjects, the occipital cortex plays an important role in Braille reading, suggesting that there is cross-modal plasticity. Functional recovery frequently occurs following a CNS injury such as stroke. Motor recovery from stroke may be associated with the adjacent cortical areas taking over the function of the damaged areas or utilization of alternative motor pathways. The ipsilateral motor pathway may mediate motor recovery in patients who undergo hemispherectomy early in life and in children with hemiplegic cerebral palsy, but it remains to be determined if it plays a significant role in the recovery of adult stroke. One of the challenges in stroke recovery is to identify which of the many neuroimaging and neurophysiological changes demonstrated are important in mediating recovery. The mechanism of plasticity probably differs depending on the time frame. Rapid changes in motor representations within minutes are likely due to unmasking of latent synapses involving modulation of GABAergic inhibition. Changes over a longer time likely involve other additional mechanisms such as long-term potentiation, axonal regeneration and sprouting. While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain. An understanding of the mechanism of plasticity will help to develop treatment programs to improve functional outcome.

Aging↗
PubMed2002

Cholinergic influences on use-dependent plasticity.

Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double-blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system.

Administration, Cutaneous↗
PubMed2001

Mechanisms underlying rapid experience-dependent plasticity in the human visual cortex.

Visual deprivation induces a rapid increase in visual cortex excitability that may result in better consolidation of spatial memory in animals and in lower visual recognition thresholds in humans. gamma-Aminobutyric acid (GABA)ergic, N-methyl-d-aspartate (NMDA), and cholinergic receptors are thought to be involved in visual cortex plasticity in animal studies. Here, we used a pharmacological approach and found that lorazepam (which enhances GABA(A) receptor function by acting as a positive allosteric modulator), dextrometorphan (NMDA receptor antagonist), and scopolamine (muscarinic receptor antagonist) blocked rapid plastic changes associated with light deprivation. These findings suggest the involvement of GABA, NMDA, and cholinergic receptors in rapid experience-dependent plasticity in the human visual cortex.

Adult↗
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↗