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Biomedical subjects

Felipe Fregni

Publications and source records attributed to Felipe Fregni.

At least 19 recordsLinked to original sources

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↗

[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↗

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↗

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↗

Attentional modulation of emotional stimulus processing: an fMRI study using emotional expectancy.

We used emotional expectancy to study attentional modulation in the processing of emotional stimuli. During functional magnetic resonance imaging (fMRI), volunteers saw emotional and neutral expectancy cues signaling the subsequent presentation of corresponding emotional or neutral pictorial stimuli. As a control, emotional and neutral pictures were presented without preceding expectancy cue, resulting in a 2 x 2 factorial design with the factors "expectancy" and "emotion." Statistical analysis revealed a significant positive interaction effect between these factors in the medial prefrontal cortex (MPFC, Brodmann area [BA] 9/10), amygdala, and dorsal midbrain. In all these regions, expectancy augmented the neural response to emotional but not to neutral pictures. Time course analysis of raw data suggests that this augmented activation was not preceded by baseline increases in MPFC and amygdala during the period of emotional expectancy. In a post-scanning session, the paradigm was presented for a second time to allow emotional intensity rating. Again, a significant interaction between expectancy and emotion was observed, with intensity ratings specifically enhanced in emotional photographs preceded by expectancy. There was a positive correlation between intensity ratings and blood oxygenation level-dependent (BOLD) signals in the left amygdala. We conclude that specific components of the emotion network show enhanced activation in response to emotional stimuli when these are preceded by expectancy. This enhancement effect is not present in neutral pictures and might parallel accentuated subjective feeling states.

Adult↗

A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy.

PURPOSE: To study the effects of cathodal DC polarization in patients with refractory epilepsy and malformations of cortical development (MCDs) as indexed by seizure frequency and epileptiform EEG discharges. METHODS: Nineteen patients with MCDs and refractory epilepsy underwent one session of DC polarization (20 min, 1 mA) targeting the epileptogenic focus. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after, and 15 and 30 days after either sham or active DC polarization. Seizure frequency after the treatment was compared with baseline. RESULTS: Active compared with sham DC polarization was associated with a significant reduction in the number of epileptiform discharges [mean ED reduction of -64.3% (95% CI, -122.5% to -6.0%) for the active treatment group and -5.8% (95% CI, -26.8% to 15.2%) for the sham treatment group]. A trend (p = 0.06) was noted for decrease in seizure frequency after active compared with sham treatment [mean seizure frequency decrease of -44.0% (95% CI, -95.0% to 7.1%) for the active treatment group and -11.1% (95% CI, -22.2% to 44.4%) for the sham treatment group]. CONCLUSIONS: This randomized, controlled study shows that cathodal DC polarization does not induce seizures and is well tolerated in patients with refractory epilepsy and MCDs. Furthermore, the results suggest that this technique might have an antiepileptic effect based on clinical and electrophysiological criteria.

Adult↗

Effect of low-frequency transcranial magnetic stimulation on an affective go/no-go task in patients with major depression: role of stimulation site and depression severity.

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a therapeutic tool in major depression. However, a means to assess the effects of a single rTMS session on mood to guide subsequent sessions would be desirable. The present study examined the effects of a single rTMS session on an affective go/no-go task known to measure emotional-cognitive deficits associated with major depression. Ten patients with an acute episode of unipolar major depression and eight partially or completely remitted (improved) patients underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior to task performance. TMS over the mesial occipital cortex was used as a control. We observed significantly improved performance in depressed patients following right prefrontal rTMS. This beneficial effect declined with decreasing depression severity and tended to reverse in the improved group. Left prefrontal rTMS had no significant effect in the depressed group, but it resulted in impaired task performance in the improved group. Our findings indicate that the acute response of depressed patients to rTMS varies with the stimulation site and depression severity. Further studies are needed to determine whether the present paradigm could be used to predict antidepressant treatment success or to individualize stimulation parameters according to specific pathology.

Antidepressive Agents↗

Dissociable networks for the expectancy and perception of emotional stimuli in the human brain.

William James posited that comparable brain regions were implicated in the anticipation and perception of a stimulus; however, dissociable networks (at least in part) may also underlie these processes. Recent functional neuroimaging studies have addressed this issue by comparing brain systems associated with the expectancy and perception of visual, tactile, nociceptive, and reward stimuli. In the present fMRI study, we addressed this issue in the domain of pictorial emotional stimuli (IAPS). Our paradigm involved the experimental conditions emotional expectancy, neutral expectancy, emotional picture perception, and neutral picture perception. Specifically, the emotional expectancy cue was uncertain in that it did not provide additional information regarding the positive or negative valence of the subsequent picture. Neutral expectancy and neutral picture perception served as control conditions, allowing the identification of expectancy and perception effects specific for emotion processing. To avoid contamination of the perception conditions by the preceding expectancy periods, 50% of the pictorial stimuli were presented without preceding expectancy cues. We found that the emotional expectancy cue specifically produced activation in the supracallosal anterior cingulate, cingulate motor area, and parieto-occipital sulcus. These regions were not significantly activated by emotional picture perception which recruited a different neuronal network, including the amygdala, insula, medial and lateral prefrontal cortex, cerebellum, and occipitotemporal areas. This dissociation may reflect a distinction between anticipatory and perceptive components of emotional stimulus processing.

Adult↗

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.

Aged↗

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory.

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Adult↗

Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study.

OBJECTIVE: To study the effects of repetitive transcranial magnetic stimulation (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and malformations of cortical development (MCDs). METHODS: Eight patients with MCD and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600 pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after as well as 15 and 30 days after rTMS treatment. RESULTS: Stimulation significantly decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction of 46.4%, 95% CI 12.7-80.2%, and mean reduction of 42.1%, 95% CI 8.2-75.7%, respectively). This was associated with a significant reduction in the number of seizures reported as compared with the 4-week period preceding rTMS (mean reduction of 57.3%, 95% CI 33.1-80.3%, and mean reduction of 51.2%, 95% CI 27.9-74.9%, respectively). CONCLUSION: This open study shows a significant antiepileptic effect of rTMS based on clinical and electrophysiological criteria and supports the therapeutic utility of rTMS for patients with well-localized epileptogenic cortical malformations.

Adolescent↗

Left prefrontal repetitive transcranial magnetic stimulation impairs performance in affective go/no-go task.

Functional neuroimaging studies have associated affective go/no-go function with lateral prefrontal activation, but they have not established a causal role and have not determined whether one hemisphere is predominantly engaged. In the present study, 11 normal volunteers underwent slow repetitive transcranial magnetic stimulation of the left and right dorsolateral prefrontal cortex, and the occipital cortex prior to performance of a picture-based affective go/no-go task. We found an interfering effect of left prefrontal repetitive transcranial magnetic stimulation compared with both right prefrontal and occipital repetitive transcranial magnetic stimulation. This impairment concerned positive and negative task stimuli to a similar extent, and tended to be greater in shift compared with nonshift blocks. Our findings demonstrate a functionally relevant lateralization of the prefrontal contribution to affective go/no-go tasks.

Adult↗

Transient disruption of ventrolateral prefrontal cortex during verbal encoding affects subsequent memory performance.

Episodic memory supports conscious remembrance of everyday experience. Prior functional neuroimaging data indicate that episodic encoding during phonological task performance is correlated with activation in bilateral posterior ventrolateral prefrontal cortex (pVLPFC), although uncertainty remains regarding whether these prefrontal regions make necessary contributions to episodic memory formation. Using functional MRI data to guide application of single-pulse transcranial magnetic stimulation (spTMS), this study examined the necessity of left and right pVLPFC for episodic encoding (as expressed through subsequent memory performance). To assess the timing of critical computations, pVLPFC function was transiently disrupted at different poststimulus onset times while subjects made syllable decisions about visually presented familiar and unfamiliar words; subsequent memory for these stimuli was measured. Results revealed that left pVLPFC disruption during encoding of familiar words impaired subsequent memory, expressed as a decline in recognition confidence, with disruption being maximal at 380 ms after stimulus onset. In contrast, right pVLPFC disruption facilitated subsequent memory for familiar words, expressed as an increase in medium confidence recognition, with this facilitation being maximal at 380 ms. Finally, phonological (syllable) decision accuracy was facilitated by right pVLPFC disruption, with this effect being maximal at 340 ms, but was unaffected by left pVLPFC disruption. These findings suggest that left pVLPFC mechanisms onset between 300 and 400 ms during phonological processing of words, with these mechanisms appearing necessary for effective episodic encoding. In contrast, disruption of correlated mechanisms in right pVLPFC facilitates encoding, perhaps by inducing a functional shift in the mechanisms engaged during learning.

Adolescent↗

Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Adult↗

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.

Aged↗

Transcranial magnetic stimulation for the treatment of depression in neurologic disorders.

Depression is commonly associated with neurologic disorders. Although depression in neurologic conditions often is associated with a negative impact on quality of life, it frequently is poorly managed. Some factors, such as a multidrug regimen, lack of efficacy, and side effects of antidepressants may explain why depression is not adequately treated in patients with neurologic disorders. Therefore, this population needs new approaches for depression treatment, and repetitive transcranial magnetic stimulation (rTMS) may be one of them because it has been shown to be effective for the treatment of depression alone and depression in certain neurologic diseases such as Parkinson's disease and stroke. rTMS is a noninvasive, focal, and painless treatment associated with few, mild side effects. It may be effective in the treatment of neurologic diseases such as Parkinson's disease, stroke, and epilepsy. In this paper, we discuss the potential risks and benefits of rTMS treatment for depression in Parkinson's disease, epilepsy, stroke, multiple sclerosis, and Alzheimer's disease. Lastly, a framework that includes the parameters of stimulation (intensity, frequency, number of pulses, and site of stimulation) for the treatment of depression in neurologic diseases is proposed.

Depressive Disorder↗