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Biomedical subjects

Alvaro Pascual-Leone

Publications and source records attributed to Alvaro Pascual-Leone.

At least 91 records · Page 5Linked to original sources

Modulation of right motor cortex excitability without awareness following presentation of masked self-images.

The neural substrates of self-awareness have been studied with a variety of neurophysiological and behavioral tools. In the present study, unconscious modulation of corticospinal excitability following presentation of self-images was probed with transcranial magnetic stimulation (TMS). TMS-induced motor evoked potentials (MEP) were collected from the contralateral first dorsal interosseus (FDI) muscle while subjects viewed masked pictures of their own face. MEP amplitudes were compared to those obtained when pictures of strangers were masked. Masked self-images induced a relative increase in corticospinal excitability when TMS was applied to the right primary motor cortex. These results demonstrate the utility of TMS to probe unconscious processing and support the notion of hemispheric asymmetry in the processing of self-images.

Adult↗

Transcranial magnetic stimulation as a complementary treatment for aphasia.

Functional brain imaging with nonfluent aphasia patients has shown increased cortical activation (perhaps "overactivation") in right (R) hemisphere language homologues. These areas of overactivation may represent a maladaptive strategy that interferes with, rather than promotes, aphasia recovery. Repetitive transcranial magnetic stimulation (rTMS) is a painless, noninvasive procedure that utilizes magnetic fields to create electric currents in discrete brain areas affecting about a 1-cm square area of cortex. Slow frequency, 1 Hz rTMS reduces cortical excitability. When rTMS is applied to an appropriate cortical region, it may suppress the possible overactivation and thus modulate a distributed neural network for language. We provide information on rTMS and report preliminary results following rTMS application to R Broca's area (posterior, R pars triangularis) in four stroke patients with nonfluent aphasia (5-11 years after left hemisphere stroke). Following 10 rTMS treatments, significant improvement in naming pictures was observed. This form of rTMS may provide a novel, complementary treatment for aphasia.

Aphasia↗

Visual hallucinations during prolonged blindfolding in sighted subjects.

The authors report the occurrence of visual hallucinations of varying complexity in 13 normal subjects after sudden, complete, and prolonged visual deprivation. The subjects were all healthy individuals with no history of cognitive dysfunction, psychosis, or ocular pathology. They wore a specially designed blindfold for a period of five consecutive days (96 hours) and were asked to record their daily experiences using a hand-held microcassette recorder. Ten (77%) of the subjects reported visual hallucinations, which were both simple (bright spots of light) and complex (faces, landscapes, ornate objects). The onset of hallucinations was generally after the first day of blindfolding. Subjects were insightful as to their unreal nature. These results indicate that rapid and complete visual deprivation is sufficient to induce visual hallucinations in normal subjects.

Adult↗

Three-dimensional head model simulation of transcranial magnetic stimulation.

This paper presents a finite element method used to evaluate the induced current density in a realistic model of the human head exposed to a time varying magnetic field. The tissue electric properties were varied to ascertain their influence on the induced currents. Current density magnitude and vector plots were generated throughout the tissue layers to determine the effects of tissue boundaries on the field. The current density magnitude correlated to the conductivity of the tissue in all the cases tested except where the tissue permittivity was raised to a level to allow for displacement currents. In this case, the permittivity of the tissue was the dominant factor. Current density components normal to the tissue interface were shown to exist in all solutions within the cortex contrary to the predictions of present models that rely on symmetrical geometries. Additionally, modifications in the cortical geometry were shown to perturb the field so that the site of activation could be altered in diseased patient populations. Finally, by varying the tissue permittivity values and the source frequency, we tested the effects of alpha dispersion theories on transcranial magnetic stimulation.

Adult↗

Modulation of premotor mirror neuron activity during observation of unpredictable grasping movements.

Using transcranial magnetic stimulation, we explored the properties of premotor mirror neurons during the passive observation of a reaching-grasping movement in human subjects. Two different experiments were run using video-clips as visual stimuli. Video-clips showed a normally performed (control stimulus) or an anomalous reaching-grasping movement executed by delaying the time of the appearance of the maximal finger aperture (experiment 1), or substituting it with an unpredictable closure (experiment 2). Motor evoked potentials were recorded at different time-points during the observation of the video-clips. Profiles of cortical excitability were drawn and compared with the kinematic profiles of the corresponding movement. Passive observation of the natural movement evoked a profile of cortical excitability that is in concordance with the timing of the kinematic profile of the shown finger movements. Observation of the uncommon movements did not exert any modulation (experiment 1) or evoked an activity that matched, at the beginning, the modulation obtained with observation of the natural movement (experiment 2). Results show that the resonant motor plan is loaded as whole at the beginning of observation and once started tends to proceed to its completion regardless of changes to the visual cues. The results exclude the possibility of a temporal fragmentation of the resonant plan, because activation of different populations of mirror neurons for each phase of the ongoing action. They further support the notion of the role of the mirror system as neural substrate for the observing-execution matching system and extend the current knowledge regarding mechanisms that trigger the internal representation of an action.

Adult↗

All talk and no action: a transcranial magnetic stimulation study of motor cortex activation during action word production.

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used single- and paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category.

Acoustic Stimulation↗

No deterioration of cognitive performance in an aggressive unilateral and bilateral antidepressant rTMS add-on trial.

BACKGROUND: Cognitive functions were assessed before and following a course of repetitive transcranial magnetic stimulation (rTMS) in patients with depression participating in a sham-controlled, randomized trial of rTMS as adjunct to antidepressant treatment. METHOD: Forty-one medicated inpatients with a DSM-IV diagnosis of a depressive episode were consecutively randomly assigned to 1 of 3 groups comparing 2 active rTMS conditions with sham stimulation. The rTMS was applied either at high frequency over the left dorsolateral-prefrontal cortex (DLPFC) (10 sessions x 10 trains x 10 seconds 20 Hz at 100% motor threshold [MT], 90-second intertrain interval) or in a combined high- and low-frequency manner to the left and right DLPFC, respectively (10 sessions x 1 train x 10 minutes at 120% MT). Thirty-eight patients completed a neuropsychological test battery at baseline and following day 14. The cognitive assessment focused on motor skills, attention, executive functions, learning, and memory. Data were collected from November 1999 to August 2002. RESULTS: Active treatment groups did not differ with respect to assessed cognitive measures and thus were pooled. A comparison of short-term changes (baseline-day 14) in neuropsychological performance revealed a more favorable time course of the actively treated patients for encoding in the verbal memory test compared with the sham-stimulated patients. CONCLUSIONS: Unilateral rTMS as well as bilateral combined rTMS revealed no detrimental effects on cognition, as compared with the sham group. Moreover, neither the add-on design nor the used aggressive parameters had a negative impact on cognitive measures in comparison with sham. Repetitive transcranial magnetic stimulation might have mild beneficial cognitive effects partly independent of its antidepressant efficacy.

Adult↗

Anti-kindling effect of slow repetitive transcranial magnetic stimulation in rats.

The cerebrospinal fluid (CSF) of animals exposed to electroconvulsive shock (ECS) has anticonvulsant properties when injected into naive animals. The present study investigated whether the CSF of humans exposed to 1 or 10 Hz repetitive transcranial magnetic stimulation (rTMS) has similar properties. Using a 4 day rat flurothyl kindling seizure model we found that the kindling rate was significantly decreased by intraventricular injection of CSF from depressed patients exposed to 1 Hz rTMS. The CSF from patients that underwent 10 Hz rTMS showed a trend toward an increased kindling rate. These results support the similarity of ECS and rTMS and suggest that 1 Hz and 10 Hz rTMS produce distinct physiologic changes.

Adult↗

Transcranial magnetic stimulation: studying motor neurophysiology of psychiatric disorders.

RATIONALE: Transcranial magnetic stimulation (TMS) is a noninvasive tool that directly stimulates cortical neurons by inducing magnetic and secondary electric fields. Traditionally TMS has been used to study the motor neurophysiology of healthy subjects and those with neurological disorders. OBJECTIVE: Given the known motor dysfunctions in many psychiatric disorders supplemental usage of TMS to study the underlying pathophysiology of certain psychiatric disorders and to assess treatment outcomes is underway. Such studies include examination of motor neuronal membrane, corticospinal and intracortical excitability. Our objective is to overview the past findings. METHODS: We review the past literature that used TMS as an assessment tool in psychiatric disorders such as schizophrenia, mood disorders, Tourette's syndrome, obsessive-compulsive disorder, attention-deficit hyperactivity disorder, and substance abuse. RESULTS: While the findings are still preliminary due to small sample-size, inconsistent patient population (diagnosis, medication), differences in methodology between research groups, studies restricted to the motor region and possible lack of sensitivity and specificity, the studies are yielding interesting results which could potentially lead to trait- and state-markers of psychiatric disorders. CONCLUSIONS: Future studies using TMS alone or in combination with other neuroimaging techniques promise to further expand the application of TMS from studies of motor excitability to higher cognitive functions.

Electric Stimulation Therapy↗

Cancellation of visuoparietal lesion-induced spatial neglect.

In humans lesions of right visuoparietal cortex induce a neglect of the contralesional visual field that is characterized in its mild form by inattentiveness to objects and events and, in its more severe form, by a condition that has many features that are indistinguishable from blindness. Here we show that spatial neglect can be induced in cats by lesions of posterior and inferior visuoparietal cortex, and that the lesion-induced neglect can be cancelled by cooling deactivation of the same region in the opposite hemisphere.

Animals↗

Modulation of intracortical neuronal circuits in human hand motor area by digit stimulation.

We investigated the changes in intracortical neuronal circuits of the hand motor cortex following sensory stimulation of the fingers in 11 healthy subjects. Motor evoked potentials (MEPs) were recorded from intrinsic hand muscles (right first dorsal interosseous and abductor digiti minimi muscles). Electrical stimulation was applied to a digit near (homotopic) or distant (heterotopic stimulation) from each muscle. The right index or little finger was stimulated electrically, followed by single- or paired-pulse transcranial magnetic stimulation (TMS) at an interval of 25, 200, 600, 1,000 or 1,400 ms. Paired-pulse TMS was applied with interstimuli intervals of 2 ms or 12 ms and was expected to stimulate inhibitory or facilitatory intracortical circuits, respectively. MEPs induced by single-pulse TMS were significantly suppressed 200, 600, and 1,000 ms after heterotopic and homotopic stimuli. Intracortical facilitation was significantly enhanced only after homotopic stimuli and such enhancement was maximal 200 ms after digit stimulation. Intracortical inhibition was slightly weakened after homotopic stimulation but this effect did not reach statistical significance ( P=0.25). Our results show that sensory feedback can modify intracortical and corticospinal motor excitability and that intracortical facilitation can be enhanced in a topographic-specific way especially at long latencies. These findings suggest that indirect pathways, probably through somatosensory cortex and other areas, enhance intracortical motor excitability in a somatotopically organized manner.

Adult↗

The role of motion direction selective extrastriate regions in reading: a transcranial magnetic stimulation study.

Why reading ability is correlated with motion processing ability is perplexing. Activity in motion direction processing regions (Area V5/MT+) was perturbed by means of repetitive transcranial magnetic stimulation (rTMS) to examine its effect on reading. A functional probe (significant shortening of the motion aftereffect) was used to identify Area V5/MT+. Right-handed participants (8 m, 8 f) received three 7.5 min blocks of rTMS, after which two phonological and one orthographic reading tasks were administered. Application of rTMS to Area V5/MT+ (as compared to a non-rTMS baseline) significantly decreased performance only during non-word naming. The pattern of naming errors and the absence of deficits on the second phonological task were not consistent with a role for Area V5/MT+ in phonological decoding. Instead, its role in reading may be limited to image stabilization and/or letter localization.

Adult↗

Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.

Adult↗

Ipsilateral motor cortex activation on functional magnetic resonance imaging during unilateral hand movements is related to interhemispheric interactions.

Distal, unilateral hand movements can be associated with activation of both sensorimotor cortices on functional MRI. The neurophysiological significance of the ipsilateral activation remains unclear. We examined 10 healthy right-handed subjects with and without activation of the ipsilateral sensorimotor area during unilateral index-finger movements, to examine ipsilateral, uncrossed-descending pathways and interhemispheric interaction between bilateral motor areas, using transcranial magnetic stimulation (TMS). No subject showed ipsilateral activation during right hand movement. Five subjects showed ipsilateral sensorimotor cortical activation during left hand movement (IpsiLM1). In these subjects, paired-pulse TMS revealed a significant interhemispheric inhibition of the left motor cortex by the right hemisphere that was not present in the 5 subjects without IpsiLM1. Neither ipsilateral MEPs nor ipsilateral silent periods were evoked by TMS in any subjects. Our observation suggests that IpsiLM1 is not associated with the presence of ipsilateral uncrossed-descending projections. Instead, IpsiLM1 may reveal an enhanced interhemispheric inhibition from the right hemisphere upon the left to suppress superfluous, excessive activation.

Adult↗

Transcranial magnetic stimulation in neurology.

Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue, including cerebral cortex, spinal roots, and cranial and peripheral nerves. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Single stimuli can depolarise neurons and evoke measurable effects. Trains of stimuli (repetitive TMS) can modify excitability of the cerebral cortex at the stimulated site and also at remote areas along functional anatomical connections. TMS might provide novel insights into the pathophysiology of the neural circuitry underlying neurological and psychiatric disorders, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases. This potential is supported by the available studies, but more work is needed to establish the role of TMS in clinical neurology.

Brain↗