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Biomedical subjects

A Pascual-Leone

Publications and source records attributed to A Pascual-Leone.

At least 19 recordsLinked to original sources

Transcranial magnetic stimulation as therapy for depression and other disorders.

OBJECTIVE: To provide an overview of the progress and prospects of transcranial magnetic stimulation as a psychiatric therapy for depression. METHOD: Published and unpublished studies of the usefulness of transcranial magnetic stimulation as a therapy for depression were assessed, and characterised in terms of a consistent measure of dosage. Additional information was obtained through correspondence, personal meetings and visits to facilities. RESULTS: Transcranial magnetic stimulation, a means for inducing small regional currents in the brain, has been used in clinical neurology for some time, and can be used on conscious subjects with minimal side-effects. Early researchers noticed transient mood effects on people receiving this treatment, which prompted several inconclusive investigations of its effects on depressed patients. More recently, knowledge of functional abnormalities associated with depression has led to trials using repetitive transcranial magnetic stimulation to stimulate underactive left prefrontal regions, an approach which has produced short-term benefits for some subjects. The higher dosage delivered by high-frequency repetitive transcranial magnetic stimulation appears to produce greater benefits; scope exists for more conclusive studies based on extended treatment periods. CONCLUSIONS: Repetitive transcranial magnetic stimulation is a promising technology. The reviewed evidence indicates that it may be useful in the treatment of depression, and perhaps other disorders which are associated with regional hypometabolism. Should repetitive transcranial magnetic stimulation prove an effective, non-invasive, drug-free treatment for depression, a range of disorders could be similarly treatable.

Depressive Disorder

Reorganization of human cortical motor output maps following traumatic forearm amputation.

We report the results of serial transcranial magnetic stimulation mapping of cortical motor outputs to the face and upper extremity in a subject studied before and repeatedly after traumatic amputation of the right arm immediately below the elbow. The results of the mapping studies illustrate the time course of plastic changes in the motor cortical representation in humans following a traumatic amputation and allow the correlation of subjective perceptions of phantom limbs with the reorganization of cortical outputs.

Accidents, Traffic

Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression.

BACKGROUND: Lesion and neuroimaging studies suggest that left prefrontal lobe dysfunction is pathophysiologically linked to depression. Rapid-rate transcranial magnetic stimulation (rTMS) to prefrontal structures has a lateralised effect on mood in normal volunteers, and several preliminary studies suggest a beneficial effect of rTMS on depression. However, adequately controlled studies have not been conducted. METHODS: We have studied the effects of focal rTMS on the depressive symptoms in 17 patients with medication-resistant depression of psychotic subtype. The study was designed as a multiple cross-over, randomised placebo-controlled trial. Sham rTMS and stimulation of different cortical areas were used as controls. FINDINGS: Left dorsolateral prefrontal cortex rTMS resulted in a significant decrease in scores on the Hamilton depression rating scale HDRS (from 25.2 to 13.8) and the self-rated Beck questionnaire BQ (from 47.9 to 25.7). 11 of the 17 patients showed pronounced improvement that lasted for about 2 weeks after 5 days of daily rTMS sessions. No patient experienced any significant undesirable side-effects. INTERPRETATION: Our findings emphasise the role of the left dorsolateral prefrontal cortex in depression, and suggest that rTMS of the left dorsolateral prefrontal cortex might become a safe, non-convulsive alternative to electroconvulsive treatment in depression.

Adult

Activation of the primary visual cortex by Braille reading in blind subjects.

Primary visual cortex receives visual input from the eyes through the lateral geniculate nuclei, but is not known to receive input from other sensory modalities. Its level of activity, both at rest and during auditory or tactile tasks, is higher in blind subjects than in normal controls, suggesting that it can subserve nonvisual functions; however, a direct effect of non-visual tasks on activation has not been demonstrated. To determine whether the visual cortex receives input from the somatosensory system we used positron emission tomography (PET) to measure activation during tactile discrimination tasks in normal subjects and in Braille readers blinded in early life. Blind subjects showed activation of primary and secondary visual cortical areas during tactile tasks, whereas normal controls showed deactivation. A simple tactile stimulus that did not require discrimination produced no activation of visual areas in either group. Thus in blind subjects, cortical areas normally reserved for vision may be activated by other sensory modalities.

Blindness

The role of the dorsolateral prefrontal cortex in implicit procedural learning.

We studied the role of the dorsolateral prefrontal cortex in procedural learning. Normal subjects completed several blocks of a serial reaction time task using only one hand without or with concurrent non-invasive repetitive transcranial magnetic stimulation. To disrupt their function transiently, stimulation was applied at low intensity over the supplementary motor area or over the dorsolateral prefrontal cortex contralateral or ipsilateral to the hand used for the test. Stimulation to the contralateral dorsolateral prefrontal cortex markedly impaired procedural implicit learning, as documented by the lack of significant change in response times during the task. Stimulation over the other areas did not interfere with learning. These results support the notion of a critical role of contralateral dorsolateral prefrontal structures in learning of motor sequences.

Adult

Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex.

Rapid-rate transcranial magnetic stimulation (rTMS) was administered to 10 healthy volunteers on different days over the right or left prefrontal cortex, midfrontal cortex, occipital cortex, or cerebellum. Mood (self-rated), reaction time, and hormone levels were serially measured. Consistent with a previous study, comparison of hemispheres revealed significant associations with decreased happiness after left prefrontal rTMS and decreased sadness after right prefrontal rTMS. Stimulation of all three prefrontal regions, but not the occipital or cerebellar regions, was associated with increases in serum thyroid-stimulating hormone. There was no effect on serum prolactin. rTMS applied to prefrontal cortex is safe and well tolerated and produces regionally and laterally specific changes in mood and neuroendocrine measures in healthy adults. rTMS is a promising tool for investigating prefrontal cortex functions.

Adult

Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood.

We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

Adult

The role of reading activity on the modulation of motor cortical outputs to the reading hand in Braille readers.

We studied the cortical motor output maps of the first dorsal interosseous (FDI) of both hands and the abductor digiti minimi of the reading hand in 6 blind proficient Braille readers. The maps were generated using transcranial magnetic stimulation. We compared the maps obtained on a day in which they worked as Braille proofreaders (reading Braille for approximately 6 hours) with the maps obtained on a day they took off from work. On the work day, the maps for the FDI of the reading hand were significantly larger after the working shift than in the morning after having been off work for 2 days. These changes were not seen for the same muscle on the day off work or on any of the 2 days in the other two muscles studied. These results illustrate the rapid modulation in motor cortical outputs in relation to preceding activity and emphasize the importance of precise timing in studies of the neurophysiological correlates of skill acquisition.

Adult

Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex.

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution of the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.

Adult

Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills.

1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Induction of errors in a delayed response task by repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.

We used repetitive transcranial magnetic stimulation to study the function of the dorsolateral frontal cortex in a delayed response task in 10 normal volunteers. Unilateral stimulation of right or left prefrontal cortex during the delay period between instruction and execution cues led to a significantly greater number of response errors than stimulation of motor cortex or in unstimulated trials. Repetitive transcranial stimulation of appropriate intensity and frequency seems to disrupt the function of mnemonic cells in the prefrontal cortex and is useful for the study of the role of the prefrontal cortex in short-term motor memory.

Adult

Induction of a recall deficit by rapid-rate transcranial magnetic stimulation.

We used rapid-rate, repetitive transcranial magnetic stimulation (rTMS) for the noninvasive study of verbal recall. Five right-handed normal subjects were studied. Recall followed immediately after presentation of a 12-word list. Focal rTMS was applied with a figure eight coil in trains of 500 ms duration to F7, F8, T5, T6, P3, P4, or O1, O2 at latencies of 0, 250, 500, or 1000 ms during word list presentation. Recall was consistently significantly diminished only after left mid-temporal and bilateral dorsofrontal rTMS at both 0 and 250 ms latencies. We conclude that rTMS may be useful as a non-invasive tool for the study of verbal memory processes.

Adolescent

Modulation of cortical motor output maps during development of implicit and explicit knowledge.

The excitability of the human motor cortex during the development of implicit and declarative knowledge of a motor task was examined. During a serial reaction time test, subjects developed implicit knowledge of the test sequence, which was reflected by diminishing response times. Motor cortical mapping with transcranial magnetic stimulation revealed that the cortical output maps to the muscles involved in the task became progressively larger until explicit knowledge was achieved, after which they returned to their baseline topography. These results illustrate the rapid functional plasticity of cortical outputs associated with learning and with the transfer of knowledge from an implicit to explicit state.

Brain Mapping

Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation.

We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease.

Adult

Cortical motor representation of the ipsilateral hand and arm.

We sought to determine whether motor evoked potentials (MEPs) as well as silent periods could be produced in hand and shoulder muscles by transcranial magnetic stimulation (TMS) of the ipsilateral cerebral hemisphere and, if so, whether their cortical representations could be mapped with respect to those of contralateral muscles. In six normal subjects, we delivered ten stimuli each to a grid of sites 1 cm apart on the scalp. The EMG was recorded and averaged from the contralateral first dorsal interosseous (FDI) and risorius (facial) muscles at rest and the ipsilateral FDI muscle, which was voluntarily contracted. In four of these subjects and an additional subject, we used the same mapping technique and recorded from the deltoid muscle on the right and left sides and the contralateral FDI during activation of the ipsilateral deltoid. In all subjects, the cortical representation of the contralateral risorius was anterolateral to that of the FDI. The contralateral deltoid could be activated in only three subjects. In them, its representation was slightly medial to that of the FDI. All subjects had at least one scalp site where TMS produced MEPs in the ipsilateral FDI. Two subjects had rich ipsilateral hand representations with multiple ipsilateral MEP sites. Both had ipsilateral MEP sites near the representation of the contralateral FDI, but the largest ipsilateral MEPs occurred with TMS at more lateral sites, which were near the representation of the contralateral risorius. In these subjects, the ipsilateral deltoid was preferentially activated at sites medial and posterior to those activating the contralateral muscle. Ipsilateral TMS also produced silent periods in the FDI in all subjects. These silent periods were much more frequent than the ipsilateral MEPs and tended to occur with TMS near the representation of the contralateral FDI. The excitatory cortical representation of the ipsilateral arm muscles is accessible to TMS in normal subjects and is different from that of the homologous contralateral muscles. The hand may have two ipsilateral representations, one of which produces silent periods and the other MEPs at the same stimulus intensity.

Adult

Differentiation of sensorimotor neuronal structures responsible for induction of motor evoked potentials, attenuation in detection of somatosensory stimuli, and induction of sensation of movement by mapping of optimal current directions.

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex can evoke motor evoked potentials (MEPs), attenuation in detection of somatosensory stimuli (ADSS), and sensation of movement (SOM) referred to the same body part. In this study we tried to differentiate the substrates responsible for these effects. In 6 normal volunteers, TMS was applied with a nearly monopolar Dantec stimulator and a butterfly coil. Optimal scalp location and current direction were determined for induction of MEPs in abductor pollicis brevis (APB), first dorsal interosseous (FDI), and adductor digiti minimi (ADM); SOM in digits 2 and 5 in an ischemically paralyzed hand; and ADSS applied to digits 2 and 5. All 3 muscles' MEPs and SOM and ADSS in both digits were optimally activated from a single scalp position. In all subjects, optimal current directions for MEPs pointed anteriorly; those for ADSS and SOM pointed posteriorly. Optimal current directions showed the same progression in all subjects for MEPs (ADM, FDI, and APB from antero-lateral to antero-medial), ADSS (digit 5 postero-medial, 2 postero-lateral), and SOM (digit 1 through 5 postero-lateral to postero-medial). We conclude that neuronal networks targeting corticospinal neurons responsible for MEPs are different from those leading to SOM and ADSS (which could not be differentiated).

Adult