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Biomedical subjects

Felipe Fregni

Publications and source records attributed to Felipe Fregni.

At least 19 recordsLinked to original sources
PubMed2007

rTMS over the intraparietal sulcus disrupts numerosity processing.

It has been widely argued that the intraparietal sulcus (IPS) is involved in tasks that evoke representations of numerical magnitude, among other cognitive functions. However, the causal role of this parietal region in processing symbolic and non-symbolic numerosity has not been established. The current study used repetitive Transcranial Magnetic Stimulation (rTMS) to the left and right IPS to investigate the effects of temporary deactivations of these regions on the capacity to represent symbolic (Arabic numbers) and non-symbolic (arrays of dots) numerosities. We found that comparisons of both symbolic and non-symbolic numerosities were impaired after rTMS to the left IPS but enhanced by rTMS to the right IPS. A signature effect of numerical distance was also found: greater impairment (or lesser facilitation) when comparing numerosities of similar magnitude. The reverse pattern of impairment and enhancement was found in a control task that required judging an analogue stimulus property (ellipse orientation) but no numerosity judgements. No rTMS effects for the numerosity tasks were found when stimulating an area adjacent but distinct from the IPS, the left and right angular gyrus. These data suggest that left IPS is critical for processing symbolic and non-symbolic numerosity; this processing may thus depend on common neural mechanisms, which are distinct from mechanisms supporting the processing of analogue stimulus properties.

Adult↗
PubMed2006

Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression.

BACKGROUND: We recently showed that repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) can affect the performance in an affective go-no-go (AGN) task. We aimed to extend this previous investigation testing whether one session of anodal transcranial direct current stimulation (tDCS) of the left DLPFC, as compared with anodal occipital and sham tDCS, affects this AGN task performance. METHODS: Twenty-six patients with major depression were randomized to receive anodal tDCS of the left DLPFC, occipital cortex or sham tDCS (the cathode electrode was placed over the frontopolar area for the three conditions). An AGN task was performed immediately before and after treatment. Performance changes (pre and post-treatment) were compared across groups of treatment and correlated with Hamilton Depression Rating Scale (HDRS) score changes. RESULTS: The results show that anodal stimulation of the left DLPFC was the only condition that induced a significant improvement in task performance as shown by the increase in the number of correct responses. In addition, this effect was specific for figures with positive emotional content. This performance enhancement was not correlated with mood changes after 10 days of tDCS treatment. LIMITATIONS: Although the effects of tDCS are less focal than rTMS, it can induce a longer and stronger modulation of cortical excitability. CONCLUSIONS: Our findings suggest that left DLPFC activity is associated with positive emotional processing, confirming and extending results of previous studies that associated right DLPFC and orbito-frontal cortex activity with emotional processing. Furthermore the effects of tDCS on mood and cognition seem to be independent in major depression. These lines of evidence together shed light on the neural circuitry involved with emotional processing in major depression.

Adult↗
PubMed2006

Effects of transcranial direct current stimulation coupled with repetitive electrical stimulation on cortical spreading depression.

We have recently shown that two techniques of brain stimulation - repetitive electrical stimulation (ES) (that mimics transcranial magnetic stimulation) and transcranial direct current stimulation (tDCS) - modify the velocity of cortical spreading depression (CSD) significantly. Herein we aimed to study the effects of these two techniques combined on CSD. Thirty-two Wistar rats were divided into four groups according to the treatment: sham tDCS/sham ES, sham tDCS/1 Hz ES, anodal tDCS/1 Hz ES, cathodal tDCS/1 Hz ES. Our findings show that 1 Hz ES reduced CSD velocity, and this effect was modified by either anodal or cathodal tDCS. Anodal tDCS induced larger effects than cathodal tDCS. Hereby CSD velocity was actually increased significantly after anodal tDCS/1 Hz ES. Our results show that combining two techniques of brain stimulation can modify significantly the effects of ES alone on cortical excitability as measured by the neurophysiological parameter of cortical spreading depression and therefore provide important insights into the effects of this new approach of brain stimulation on cortical activity.

Animals↗
PubMed2006

Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients.

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.

Adult↗
PubMed2006

Immediate placebo effect in Parkinson's disease--is the subjective relief accompanied by objective improvement?

BACKGROUND: A recent well-conducted meta-analysis showed that placebo effect is associated with a possible small benefit for subjective outcomes, but has no significant effects on objective outcomes. OBJECTIVE: Herein, we aimed to investigate the immediate effects of two different types of placebo [placebo pill and sham transcranial magnetic stimulation (TMS)] in Parkinson's disease (PD) patients and compared them to the standard treatment (levodopa) in a proper randomized, double-blind, crossover clinical trial. METHODS: PD patients received three different interventions on different days: levodopa, placebo pill, and sham TMS. The motor function was assessed using simple and choice reaction time, Unified Parkinson's Disease Rating Scale (UPDRS), finger tapping, Purdue Pegboard test, time to button up, walking time and supination-pronation. The subjective motor function was measured by a visual analogue scale (VAS). RESULTS: The results showed that there was a significant motor function in the motor function only after the treatment with levodopa, but not after treatment with placebo pills or sham TMS. However, patients reported a similar subjective improvement in motor function indexed by VAS following these three treatments. CONCLUSION: These results suggest that placebo interventions in PD may have an immediate subjective sensation of improvement but result in no significant objective motor changes compared with levodopa treatment. Although physiological changes are possible after a placebo intervention, our findings suggest that the acute placebo effect in PD may be the result of the subjective change in the motor rating only.

Aged↗
PubMed2006

Comparison of repetitive transcranial magnetic stimulation and electroconvulsive therapy in unipolar non-psychotic refractory depression: a randomized, single-blind study.

Repetitive transcranial magnetic stimulation (rTMS) can induce significant antidepressant effects and, for some patients, might be an alternative to electroconvulsive therapy (ECT). The results of studies comparing the efficacy of rTMS and ECT are mixed and, therefore, comparison of these two therapies needs to be further explored. Forty-two patients aged between 18 and 65 yr, referred to ECT due to unipolar non-psychotic depression refractoriness entered the trial. They were randomly assigned to receive either rTMS or ECT. Depressive symptom changes were blindly measured by Hamilton Depression Rating Scale, Visual Analogue Scale and Clinical Global Impression at baseline, after 2 wk and after 4 wk of treatment. There was no difference in the antidepressant efficacy of ECT and rTMS. Response rates were relatively low in both groups (40% and 50% respectively), with no significant difference between them (p=0.55). Remission rates were also low for both groups (20% and 10% respectively), also with no significant difference (p=0.631). There was no significant difference in the neuropsychological test performance after either one of these therapies. Both treatments were associated with a degree of improvement in refractory depression and therefore add to the literature that rTMS can be an effective option to ECT as it is a less costly treatment and is not associated with anaesthetic and other ECT risks.

Adolescent↗
PubMed2006

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease.

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.

Aged↗
PubMed2006

Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is a non-invasive powerful method to modulate brain activity. It can enhance motor learning and working memory in healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the dominant and non-dominant primary motor cortex (M1) on hand motor performance in healthy right-handed volunteers, healthy subjects underwent one session of both sham and active anodal stimulation of the non-dominant or dominant primary motor cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand Function Test. For the non-dominant hand, active tDCS was able to improve motor function significantly-there was a significant interaction between time and condition of stimulation (p = 0.003). Post hoc tests showed a significant enhancement of JTT performance after 1 mA anodal tDCS of M1 (mean improvement of 9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84). For the dominant hand, however, neither active nor sham tDCS resulted in a significant change in motor performance. Our findings show that anodal tDCS of the non-dominant primary motor cortex results in motor function enhancement and thus confirm and extend the notion that tDCS can change behavior. We speculate that the under-use of the non-dominant hand with its associated consequences in cortical plasticity might be one of the reasons to explain motor performance enhancement in the non-dominant hand only.

Adult↗
PubMed2006

A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients.

BACKGROUND AND PURPOSE: It has been recently shown that a single session of repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can improve motor function in stroke patients; however, this improvement is short-lasting. We therefore conducted a randomized, sham-controlled, phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe. METHODS: Fifteen patients with chronic stroke were randomized to receive active or sham rTMS of the unaffected hemisphere. A blinded rater assessed motor function and corticospinal excitability at baseline, during and after 2 weeks of treatment. Safety was assessed using a neuropsychologic battery and electroencephalogram. RESULTS: Active rTMS resulted in a significant improvement of the motor function performance in the affected hand that lasted for 2 weeks. These effects were not observed in the sham rTMS group (affected and unaffected hand) and in the unaffected hand in the active rTMS group. Corticospinal excitability decreased in the stimulated, unaffected hemisphere and increased in the affected hemisphere. There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere. Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment. CONCLUSIONS: These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects. Furthermore, this increased dose of rTMS is not associated with cognitive adverse effects and/or epileptogenic activity.

Adult↗
PubMed2006

Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy.

OBJECTIVE: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. METHODS: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. RESULTS: In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. CONCLUSIONS: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. SIGNIFICANCE: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Adolescent↗
PubMed2006

Novel therapeutic approaches to the treatment of chronic abdominal visceral pain.

Chronic abdominal visceral pain (CAVP) has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS), might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

Abdominal Pain↗
PubMed2006

A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.

Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.

Adult↗
PubMed2006

[Transcranial magnetic stimulation in neuropsychology: new horizons for brain research].

This review addresses the use of transcranial magnetic stimulation as a research tool of neuropsychological functions. Transcranial magnetic stimulation is a non-invasive and painless technique to modulate brain function that can be applied to conscious human beings and is based on a variable magnetic field. Using this technique, it is possible to generate virtual transient lesions in healthy people or modulate the brain activity, increasing or decreasing the activity of the stimulated areas. In this review we discuss studies with transcranial magnetic stimulation in which broad aspects of language, memory and neuropsychological tests have been evaluated following or during the application of transcranial magnetic stimulation. We concluded that transcranial magnetic stimulation open new horizons for brain research in the neuropsychological field as transcranial magnetic stimulation allows the investigation of the relationship between focal cortical activity and behavior therefore contributing to the study of the functional brain activity.

Brain↗
PubMed2006

Transcranial magnetic stimulation and stroke: a computer-based human model study.

This paper explores how transcranial magnetic stimulation (TMS) induced currents in the brain are perturbed by electrical and anatomical changes following a stroke in its chronic stage. Multiple MRI derived finite element head models were constructed and evaluated to address the effects that strokes can have on the induced stimulating TMS currents by comparing stroke models of various sizes and geometries to a healthy head model under a number of stimulation conditions. The TMS induced currents were significantly altered for stimulation proximal to the lesion site in all of the models analyzed. The current density distributions were modified in magnitude, location, and orientation such that the population of neural elements that are stimulated will be correspondingly altered. The current perturbations were minimized for conditions tested where the coil was far removed from the lesion site, including models of stimulation contralateral to the lesioned hemisphere. The present limitations of TMS to the peri-lesional cortex are explored, ultimately concluding that conventional clinical standards for stimulation are unreliable and potentially dangerous predictors of the site and degree of stimulation when TMS is applied proximal to infarction site.

Computer Simulation↗
PubMed2006

After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression.

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 microA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS - by increasing cortical excitability - might increase the probability of migraine attack in these patients, even beyond the end of its application.

Animals↗
PubMed2006

A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy.

OBJECTIVE: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. METHODS: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. RESULTS: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group (p < 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after (p = 0.01) and at week 4 (p = 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. INTERPRETATION: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.

Adult↗
PubMed2006

A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia.

OBJECTIVE: Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia. METHODS: Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial. RESULTS: Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups. CONCLUSION: Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials.

Chronic Disease↗