Exploring paradoxical functional facilitation with TMS.
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Animals↗
Biomedical subjects
Alvaro Pascual-Leone
Publications and source records attributed to Alvaro Pascual-Leone.
Suppression of complex visual hallucinatory experiences by occipital transcranial magnetic stimulation: a case report.
Abstract We report a patient with visual hallucinations and illusions along with an associated visual field defect after bilateral ischemic damage to his occipital visual cortex. These hallucinations were long-standing and of both simple and complex (well-formed) type. Application of low frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe the neurophysiology, and possibly alleviate, visual hallucinatory experiences is discussed.
Brain Mapping↗
Transcranial magnetic stimulation as an investigative tool in the study of visual function.
Transcranial magnetic stimulation (TMS) is a novel and powerful probe to study the relationship between human brain function and behavior. TMS is being widely used to investigate memory, language, attention, learning, and motor function and is even being utilized therapeutically in the treatment of depression. Some of the earliest applications of TMS have been directed toward the investigation of human visual perception. For example, a strong TMS pulse delivered to the occipital cortex in a sighted or even blind individual can evoke the sensation of perceiving light (visual phosphenes). TMS can also be used to suppress visual perception and investigate the timing of visual information processing. Furthermore, the functional connectivity between different brain areas can be mapped using TMS, thus establishing a causal link between visual cortical function and visual perception. The present article is meant as an overview of the technique of TMS and a review of the literature as it pertains to the study of visual function. The application of TMS in the diagnosis as well as possible therapeutic use in various visual disorders is also discussed.
Electromagnetic Fields↗
Language acquisition: do as you hear.
It is not uncommon to recognize a specific action by the sound it creates. Neurons have been discovered in monkey premotor cortex that may contribute to this ability; they respond to both performing an action and hearing its action-related sound, and may be critical for communicating with others, learning gestures and even acquiring language.
Animals↗
Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.
The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.
Adolescent↗
Motor cortical excitability in schizophrenia.
BACKGROUND: Transcranial magnetic stimulation (TMS) provides a method to examine cortico-cortical motor excitability and hemispheric asymmetry in unmedicated and medicated schizophrenia patients. METHODS: Fourteen right-handed schizophrenia patients (seven on conventional neuroleptics and seven medication-free) were compared with seven right-handed, age- and gender-matched normal control subjects. Motor threshold for induction of motor-evoked potentials (MEPs) and bihemispheric intracortical inhibition and facilitation were measured with single-pulse and paired-pulse TMS. RESULTS: Medicated patients showed an approximately 5% higher motor thresholds in both hemispheres than unmedicated patients and control subjects. Normal control subjects had a nearly 10% higher threshold for the left than the right hemisphere, whereas the opposite was true for the patient groups (5-10% higher threshold on the right than the left). Medicated patients showed significantly decreased intracortical inhibition relative to unmedicated patients and control subjects. This difference was more pronounced for the right than for the left hemisphere. CONCLUSIONS: Treatment with conventional neuroleptics is associated with increased motor threshold and decreased intracortical inhibition, whereas unmedicated patients did not differ from normal control subjects on these measures; however, schizophrenia may be characterized by a reversed pattern of interhemispheric corticospinal excitability.
Adult↗
Visual cortex excitability increases during visual mental imagery--a TMS study in healthy human subjects.
Previous neuroimaging studies provided evidence that visual mental imagery relies, in part, on the primary visual cortex. We hypothesized that, analogous to the finding that motor imagery increases the excitability of motor cortex, visual imagery should increase visual cortex excitability, as indexed by a decrease in the phosphene threshold (PT). In order to test visual cortex excitability, the primary visual cortex was stimulated with transcranial magnetic stimulation (TMS), so as to elicit phosphenes in the right lower visual quadrant. Subjects performed a visual imagery task and an auditory control task. We applied TMS with increasing intensity to determine the PT for each subject. Independent of the quadrant in which subjects placed their visual images, imagery decreased PT compared to baseline PT; in contrast, the auditory task did not change PT. These findings demonstrate for the first time a short-term, task-dependent modulation of PT. These results constitute evidence that early visual areas participate in visual imagery processing.
Adult↗
Effects of musical training on speech-induced modulation in corticospinal excitability.
We investigated the effect of previous musical training on lateralization of language as indexed by the effects of reading aloud on the modulation of motor evoked potentials (MEPs) induced in the first dorsal interosseus muscles (FDI) by transcranial magnetic stimulation (TMS) of the primary motor cortex. We studied 13 right-handed subjects, seven musicians who had been playing a musical instrument for >10 years and six controls who had never studied a musical instrument. In all subjects, the amplitude of MEPs in the right FDI was facilitated by reading aloud. However, the musicians also showed significant facilitation in the left FDI, while controls did not. These results illustrate striking effects of musical training on lateralization of motor and language functions.
Adult↗
Braille character discrimination in blindfolded human subjects.
Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non-stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.
Adolescent↗
Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.
Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.
Brain↗
Repetitive transcranial magnetic stimulation of human area MT/V5 disrupts perception and storage of the motion aftereffect.
Following adaptation to a moving stimulus, the introduction of a stationary pattern creates the illusion of motion. This phenomenon, known as the motion aftereffect (MAE), can be delayed by placing a blank storage interval between the adapting and test stimuli. Human motion selective area MT/V5 has been proposed as the likely neural origin of MAEs. To examine the role of MT/V5 in perceiving and storing MAEs, we applied repetitive transcranial magnetic stimulation (rTMS) to this area during a 10s storage interval and while subjects perceived illusory motion. Our results show that rTMS disrupts perception of the MAE when it is delivered in the early parts of the storage period and when it is applied during the perceptual MAE itself. Stimulation of control regions corresponding to V1 or Cz did not affect the MAE. In addition, magnetic stimulation of dorsolateral prefrontal and posterior parietal cortices did not disrupt MAE perception. These data provide experimental support for the notion that MT/V5 subserves perception and storage of the motion aftereffect.
Adult↗
Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex.
OBJECTIVE: To investigate the modulatory effect of a subthreshold low frequency repetitive transcranial magnetic stimulation (rTMS) train on motor cortex excitability. METHODS: The study consisted of two separate experiments. Subjects received a 10 min long subthreshold 1 Hz rTMS train. In the first experiment, (single pulse paradigm), cortical excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) before and after the rTMS train. In the second experiment, a paired pulse paradigm was employed. RESULTS: Corticospinal excitability, as measured by the MEP amplitude, was reduced by the rTMS train (experiment 1), with a significant effect lasting for about 10 min after the train completion. There was notable inter-individual as well as intra-individual variability in the effect. rTMS produced a significant decrease in intra-cortical facilitation as measured by the paired pulse paradigm (experiment 2). This effect lasted for up to 15 min following the train. Intra-cortical inhibition was not significantly affected. CONCLUSIONS: Subthreshold low frequency rTMS depresses cortical excitability beyond the duration of the train. This effect seems primarily due to cortical dysfacilitation. These results have implications on the therapeutic use of rTMS.
Adult↗
Inter- and intra-individual variability of paired-pulse curves with transcranial magnetic stimulation (TMS).
OBJECTIVES: Previous studies have evaluated the variability of motor thresholds (MTs) and amplitude of motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) within and across individuals. Here we evaluate the reproducibility and inter-hemispheric variability of measures of cortical excitability using the 'conventional' paired-pulse (PP) TMS technique. METHODS: We studied PP curves of the left and right hemisphere in 10 healthy subjects on two separate days 2 weeks apart. The inter-stimulus intervals studied were 1, 3, 6, 8, 10 and 12 ms with the conditioning stimulus being 80% of the resting MT, and a single test stimulus producing MEPs of approximately 0.8 mV peak-to-peak amplitude. RESULTS: As a group, the PP curves of the left and right hemispheres, and of Day 1 and Day 2 were not significantly different. The intracortical inhibition (ICI), but not the intracortical facilitation, showed a good correlation across days within the individuals. CONCLUSIONS: Cortical excitability, particularly ICI, measured by PP TMS shows no inter-hemispheric asymmetry and is reproducible within individuals.
Adult↗
Modulation of input-output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex.
OBJECTIVES: Exploring the modulatory effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on the excitability of the motor cortex as measured by the input-output curve technique (I-O curve). METHODS: Sixteen healthy subjects participated in this experiment. On two different sessions, conducted 1 week apart, rTMS was applied either at a frequency of 20 or 1 Hz at 90% of individual motor threshold (MT) for a total of 1600 pulses each. Before and after rTMS, the cortical excitability was assessed by measuring MT and the size of motor evoked potentials (MEPs) collected at different intensities of stimulation. RESULTS: The analysis on the whole population showed a significant decrease of cortical excitability after 1 Hz rTMS and an increase after 20 Hz rTMS. A subsequent cluster analysis pointed out the presence of two distinct groups of subjects with opposite responses at the same frequency of stimulation. Significant variations on MT were found for both groups only for the facilitatory effect irrespective of the frequency of stimulation. CONCLUSIONS: The results provide further insight into interindividual differences in the effects of rTMS and suggest the existence of subpopulations with specific patterns of response to rTMS.
Adult↗
rTMS to the supplementary motor area disrupts bimanual coordination.
Bimanual coordination tasks form an essential part of our behaviour. One brain region thought to be involved in bimanual coordination is the supplementary motor area (SMA). We used repetitive transcranial magnetic stimulation (rTMS) at 1 Hz for 5 min to create a temporary virtual lesion of the rostral portion of the human SMA immediately prior to performance of a goal-directed bimanual coordination task. In two control conditions, participants underwent sham stimulation or stimulation over the primary motor cortex (MI). The experimental task was to open a drawer with the left hand, catch a ball with the right hand, and reinsert the ball into the drawer through an aperture just big enough for the ball to pass through, again with the right hand. Hence, the actions of one hand depend upon the actions of the other. We calculated time intervals between the successive component actions of one hand (unimanual intervals) and actions of both hands (bimanual intervals) and analyzed these intervals separately. Interestingly, none of the unimanual intervals were affected by the rTMS, but the variability of a critical bimanual interval--the time between the left hand opening the drawer and the right hand starting to move to catch the ball--was increased by rTMS over the rostral parts of the SMA. No such effect was seen following rTMS over MI or after sham rTMS. Our results suggest that the rostral parts of the SMA play an important role in aspects of functional bimanual tasks, which involve tight temporal coordination between different motor actions of the two hands.
Adult↗
Motor facilitation while observing hand actions: specificity of the effect and role of observer's orientation.
Action observation enhances cortico-spinal excitability. Here we tested the specificity of this effect and the role played by the orientation of the observer. Ten normal subjects observed video clips of right hand performing three different finger movements (thumb ab-/adduction, index ab-/adduction, index extens-/flexion) in two different orientations (Away, i.e., natural hand-orientation facing out from the observer; or Toward, i.e., unnatural hand-orientation facing toward the observer). Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the abductor pollicis brevis (APB) and the first dorsal interosseus (FDI) muscles. Movement direction of the index finger was recorded using force transducers. Facilitation of MEP size was significantly greater for APB during observation of thumb movements and for FDI during observation of index finger movements. Facilitation of MEP size was significantly greater when the hand presented on screen was facing out from and corresponding to that of the observer (Away orientation). The direction of the index finger movement evoked by TMS shifted toward extension/flexion versus ab-/adduction matching the observed movement. Our results give further evidence that observation of a movement enhances motor output to the muscles involved in the movement and facilitates the observed action. In addition, we provide novel evidence about the high degree of specificity of this observation-induced motor cortical modulation. The degree of modulation depends on hand orientation. The modulation is maximal when the observed action corresponds to the orientation of the observer.
Adult↗
Prediction of clinical response to transcranial magnetic stimulation for depression by baseline lateral visual-field stimulation.
OBJECTIVE: We examined whether baseline-affective responses to lateral visual-field stimulation could predict clinical responses to left, prefrontal, transcranial, magnetic stimulation (TMS) in patients who are depressed. BACKGROUND: Schiffer et al have reported that left and right lateral visual-field stimulation can often evoke different (positive versus negative) psychologic responses in a given patient. Some had improvements while looking to the left and others while looking to the right. METHODS: We asked 37 patients who were severely depressed and resistant to treatment (26 women, 11 men) to report changes in affective state in response to two pairs of goggles, each allowing vision out of either the left or right visual field. We then evaluated whether these responses predicted clinical responses to TMS as measured by the percent decrease in the Hamilton Depression Rating Scale (HDRS.4%) scores between baseline and 4 weeks (2 weeks after a 2-week course of daily TMS). RESULTS: The 20 patients who felt more improvement with right than left lateral visual-field stimulation with 45-second baseline goggle trials had a 42% (+/- SD 22.2) reduction in HSDR.4%. The 15 patients who felt more improvement looking to the left than to the right had an 11% (+/- SD 28.4) decrease in HSDR.4%. Seventy-five percent of the 20 patients in the first group had a decrease in HSDR.4% more than 20%, and 80% of the 15 in the second group had a decrease in this score of less than 20%. A two-tailed Fisher exact test showed a significant difference between the two groups (p = 0.002). CONCLUSION: Baseline affective responses to lateral visual-field stimulation predicted clinical responses to left, frontal TMS in depressed patients.
Adult↗
Transcranial magnetic stimulation and its applications in children.
Transcranial magnetic stimulation (TMS) provides a non-invasive method of induction of focal currents in the brain as well as transient modulation of the function of the targeted cortex. TMS is now widely used as a diagnostic tool in adults. In children, its application to date has been limited, even though TMS offers unique opportunities to gain insights into the neurophysiology of a child's brain. Using the single-pulse TMS technique, investigators can measure motor thresholds, motor evoked potentials, silent periods, central conduction times, and the paired-pulse curve to study central nervous system development and central motor reorganization after a cerebral lesion. Repetitive TMS (rTMS) is a novel treatment for psychiatric illness that is undergoing trials for a range of disorders in adults. Although there are rare published data on rTMS as a treatment for neuropsychiatric diseases in young persons, the benefits from TMS are nevertheless encouraging. Two important issues of pediatric TMS are safety considerations and methodology. In the future, rTMS may play an important role in the study and possibly in the therapy of children's diseases after more safety studies are completed.
Brain↗