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Biomedical subjects

A Pascual-Leone

Publications and source records attributed to A Pascual-Leone.

At least 37 records · Page 2Linked to original sources

Mapping of the human visual cortex using image-guided transcranial magnetic stimulation.

We describe a protocol using transcranial magnetic stimulation (TMS) to systematically map the visual sensations induced by focal and non-invasive stimulation of the human occipital cortex. TMS is applied with a figure of eight coil to 28 positions arranged in a 2x2-cm grid over the occipital area. A digitizing tablet connected to a PC computer running customized software, and audio and video recording are used for detailed and accurate data collection and analysis of evoked phosphenes. A frameless image-guided neuronavigational device is used to describe the position of the actual sites of the stimulation coils relative to the cortical surface. Our results show that TMS is able to elicit phosphenes in almost all sighted subjects and in a proportion of blind subjects. Evoked phosphenes are topographically organized. Despite minor inter-individual variations, the mapping results are reproducible and show good congruence among different subjects. This procedure has potential to improve our understanding of physiologic organization and plastic changes in the human visual system and to establish the degree of remaining functional visual cortex in blind subjects. Such a non-invasive method is critical for selection of suitable subjects for a cortical visual prosthesis.

Blindness↗

Degree of language lateralization determines susceptibility to unilateral brain lesions.

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Adult↗

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS.

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.

Adult↗

Modulation of spinal cord excitability by subthreshold repetitive transcranial magnetic stimulation of the primary motor cortex in humans.

Repetitive transcranial magnetic stimulation (rTMS) allows the modulation of intra-cortical excitability and may therefore affect the descending control of spinal excitability. We applied rTMS at subthreshold intensity and 1 Hz frequency for 10 min to the left primary motor cortex representation of the flexor carpi radialis muscle (FCR) in 10 subjects and assessed the H and M responses to median nerve stimulation before and after the rTMS. Following rTMS, H wave thresholds significantly reduced by approximately 20%. Maximal H but not M wave amplitude significantly increased over the baseline, so that H/M amplitude ratio was increased by 41%. Sham stimulation did not induce any noticeable change in M or H waves. Slow rTMS might facilitate monosynaptic spinal cord reflexes by inhibiting the cortico-spinal projections modulating spinal excitability.

Adult↗

Grammatical distinctions in the left frontal cortex.

Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.

Adolescent↗

Increased variability of paced finger tapping accuracy following repetitive magnetic stimulation of the cerebellum in humans.

Imaging and lesion studies suggest that the cerebellum is involved in the self-generation of timed motor responses. Using repetitive transcranial magnetic stimulation (rTMS), we studied the effects of transient disruption of the lateral or medial cerebellum on a paced-finger-tapping task (PFT). Results show greater variability on the PFT task following a 5 min train of 1 Hz rTMS to the medial cerebellum. Magnetic stimulation of the lateral cerebellum or motor cortex, and sham stimulation, had no effect on performance. Expanding the results of neuroimaging studies, these data show the causal link between activity in the medial cerebellum and the production of timed movements. This is the first demonstration of the feasibility of transiently disrupting the cerebellum by rTMS and inducing behavioral effects. This method of 'virtual lesions' can expand the study of the role of the cerebellum in motor control and cognition.

Adult↗

Phase-specific modulation of cortical motor output during movement observation.

The effects of different phases of an observed movement on the modulation of cortical motor output were studied by means of transcranial magnetic stimulation (TMS). A video-clip of a reaching-grasping action was shown and single TMS pulses were delivered during its passive observation. Times of cortical stimulation were related to the phases of the shown movement, locking them to the appearance of specific kinematic landmarks. The amplitude of the motor evoked potentials (MEPs) induced by TMS in the first dorsal interosseus (FDI) muscle was modulated by the amount of the observed finger aperture. The presence of such an effect is consistent with the notion of a mirror neuron system in premotor areas that couples action execution and action observation also in terms of temporal coding.

Acoustic Stimulation↗

Fast backprojections from the motion to the primary visual area necessary for visual awareness.

Much is known about the pathways from photoreceptors to higher visual areas in the brain. However, how we become aware of what we see or of having seen at all is a problem that has eluded neuroscience. Recordings from macaque V1 during deactivation of MT+/V5 and psychophysical studies of perceptual integration suggest that feedback from secondary visual areas to V1 is necessary for visual awareness. We used transcranial magnetic stimulation to probe the timing and function of feedback from human area MT+/V5 to V1 and found its action to be early and critical for awareness of visual motion.

Adult↗

Abnormalities of spatial and temporal sensory discrimination in writer's cramp.

Clinical observations of patients with writer's cramp suggest that abnormalities of the sensory system may be a frequent finding in this disorder. Neurophysiological data from an animal model of focal dystonia have revealed cells in somatosensory cortex with enlarged and overlapping tactile receptive fields. However, psychophysical studies so far have been unable to document a clinical correlate supporting a similar enlargement of receptive fields in humans. We compared the fingertip discrimination of the orientation of fine spatial gratings between writer's cramp and control subjects and found a significant decrease in grating sensitivity in the patients, consistent with the possibility of enlarged tactile receptive fields. In addition, we duplicated previous experiments showing an abnormality of tactile temporal discrimination. The results provide psychophysical measures which may relate to the development of sensory cortical reorganization in patients with writer's cramp.

Adult↗

Transcranial magnetic stimulation evidence of a potential role for progesterone in the modulation of premenstrual corticocortical inhibition in a woman with catamenial seizure exacerbation.

A transcranial magnetic stimulation paired-pulse paradigm was used to determine that cortical excitability was less during the late luteal phase than in the early follicular phase in a woman with epilepsy who had premenstrual seizure exacerbation. The data are consistent with the possibility that a reduction in GABA-mediated cortical inhibitory activity may be responsible. The administration of progesterone, a reproductive steroid with potent GABAergic metabolites, during the luteal phase restored cortical excitability to normal range.

Journal Article↗

Aspects of sensory guidance in sequence learning.

We explored the effects of sensory information upon procedural learning using three versions of the serial reaction-time task (SRTT): a standard task where the position of the stimulus cued the response; a non-standard task where the color of the stimulus was related to the correct response; and a combined task where both the color and position simultaneously cued the response. Despite these differences, each task had the same temporal pattern of a repeating ten-item sequence. We refer to each of these tasks based upon the cues available for guiding learning: position, color, and combined tasks. Procedural sequence learning was greater for the combined than for the other two tasks, suggesting that learning is enhanced when multiple sources of sensory information cue consistently and simultaneously for the same response. Transfer of skill occurred across all the tasks, except from the position to the color task. These results suggest that a fundamental neural algorithm is responsible for acquiring knowledge about a temporal sequence of responses rather than forming an associative relationship amongst stimuli.

Adult↗

Intracortical inhibition and facilitation in human facial motor area: difference between upper and lower facial area.

OBJECTIVE: To investigate the intracortical inhibitory and excitatory systems in the motor cortical representation of upper and lower facial muscles. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied to 7 healthy volunteers, with the interstimulus interval (ISI) between the conditioning stimulus (CS) and test stimulus, varied from 1 to 20 ms. CS was set at 90% of motor threshold. Muscle evoked potentials (MEPs) were recorded from first dorsal interosseus (FDI), orbicularis oculi (o. oculi) and mentalis muscles. RESULT: TMS evoked MEPs in o. oculi on both ipsi- and contralateral sides in all subjects. In the paired-pulse study, MEP amplitude in the mentalis decreased at short ISIs of 1-3 ms, followed by increases at 12-20 ms. These effects were similar to those in the FDI. O. oculi did not show a distinct inhibitory period at short ISIs and facilitation at long ISIs was detected but was significantly less than in FDI and mentalis. In o. oculi, there was no significant difference between the effects of ipsilateral and contralateral CS on the MEPs. CONCLUSION: The bi-hemispheric control of volitional movement and the modulation from brainstem projections appear to markedly influence intracortical inhibitory and excitatory systems in the motor cortical representation of o. oculi.

Adult↗

Transcranial magnetic stimulation coregistered with MRI: a comparison of a guided versus blind stimulation technique and its effect on evoked compound muscle action potentials.

INTRODUCTION AND METHODS: Compound muscle action potentials (CMAPs) elicited by transcranial magnetic stimulation (TMS) are characterized by enormous variability, even when attempts are made to stimulate the same scalp location. This report describes the results of a comparison of the spatial errors in coil placement and resulting CMAP characteristics using a guided and blind TMS stimulation technique. The former uses a coregistration system, which displays the intersection of the peak TMS induced electric field with the cortical surface. The latter consists of the conventional placement of the TMS coil on the optimal scalp position for activation of the first dorsal interossei (FDI) muscle. RESULTS: Guided stimulation resulted in significantly improved spatial precision for exciting the corticospinal projection to the FDI compared to blind stimulation. This improved precision of coil placement was associated with a significantly increased probability of eliciting FDI responses. Although these responses tended to have larger amplitudes and areas, the coefficient of variation between guided and blind stimulation induced CMAPs did not significantly differ. CONCLUSION: The results of this study demonstrate that guided stimulation improves the ability to precisely revisit previously stimulated cortical loci as well as increasing the probability of eliciting TMS induced CMAPs. Response variability, however, is due to factors other than coil placement.

Adult↗

Enhanced visual spatial attention ipsilateral to rTMS-induced 'virtual lesions' of human parietal cortex.

The breakdown of attentional mechanisms after brain damage can have drastic behavioral consequences, as in patients suffering from spatial neglect. While much research has concentrated on impaired attention to targets contralateral to sites of brain damage, here we report the ipsilateral enhancement of visual attention after repetitive transcranial magnetic stimulation (rTMS) of parietal cortex at parameters known to reduce cortical excitability. Normal healthy subjects received rTMS (1 Hz, 10 mins) over right or left parietal cortex. Subsequently, detection of visual stimuli contralateral to the stimulated hemisphere was consistently impaired when stimuli were also present in the opposite hemifield, mirroring the extinction phenomenon commonly observed in neglect patients. Additionally, subjects' attention to ipsilateral targets improved significantly over normal levels. These results underline the potential of focal brain dysfunction to produce behavioral improvement and give experimental support to models of interhemispheric competition in the distributed brain network for spatial attention.

Adult↗

Transcranial magnetic stimulation in young persons: a review of known cases.

There are no published data about transcranial magnetic stimulation (TMS) as a treatment for psychiatric disorders in young persons. The aim of this article is to collate available information about TMS in this population. Information was sought, by placing a message on the TMS Listserver, from investigators who had used TMS in patients 18 years of age or younger. Only one group reported experience in this area; it had treated seven patients, ages 16-18 years. Three patients had unipolar depression, three had schizophrenia, and one had bipolar disorder. Five of the seven patients had improved by the conclusion of the TMS course. Adverse events were reported in one patient. Further studies are needed first to investigate systematically the safety of TMS in children and adolescents and second to examine its potential therapeutic effects in this population.

Adolescent↗