Executive "brake failure" following deactivation of human frontal lobe

In the course of daily living, humans frequently encounter situations in which a motor activity, once initiated, becomes unnecessary or inappropriate. Under such circumstances, the ability to inhibit motor responses can be of vital importance. Although the nature of response inhibition has been studied in psychology for several decades, its neural basis remains unclear. Using transcranial magnetic stimulation, we found that temporary deactivation of the pars opercularis in the right inferior frontal gyrus selectively impairs the ability to stop an initiated action. Critically, deactivation of the same region did not affect the ability to execute responses, nor did it influence physiological arousal. These findings confirm and extend recent reports that the inferior frontal gyrus is vital for mediating response inhibition.

Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives

Background: Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach. Methods and design: The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline + tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6 weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered. Discussion: With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline. (C) 2010 Elsevier Inc. All rights reserved.

rTMS treatment for depression in Parkinson`s disease increases BOLD responses in the left prefrontal cortex

The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson`s disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic Stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex, suggesting that the activity in this area changed differently in the two treatment groups. Our findings show that antidepressant effects of rTMS and fluoxetine in PD are associated with changes in different areas of the depression-related neural network.

Abnormal Visual Activation in Parkinson`s Disease Patients

Among nonmotor symptoms observed in Parkinson`s disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyms (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD. (C) 2010 Movement Disorder Society

Neuropharmacological basis of rTMS-induced analgesia: The role of endogenous opioids

We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10 Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15 degrees C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1 mg/kg followed by a continuous infusion of 0.1 mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. (C) 2010 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.

POISSON DISTRIBUTION TO ANALYZE NEAR-THRESHOLD MOTOR EVOKED POTENTIALS

Motor unit action potentials (MUAPs) evoked by repetitive, low-intensity transcranial magnetic stimulation can be modeled as a Poisson process. A mathematical consequence of such a model is that the ratio of the variance to the mean of the amplitudes of motor evoked potentials (MEPs) should provide an estimate of the mean size of the individual MUAPs that summate to generate each MEP. We found that this is, in fact, the case. Our finding thus supports the use of the Poisson distribution to model MEP generation and indicates that this model enables characterization of the motor unit population that contributes to near-threshold MEPs. Muscle Nerve 42: 825-828, 2010

Interhemispheric Asymmetry of Corticomotor Excitability After Chronic Cerebellar Infarcts

Early after stroke, there is loss of intracortical facilitation (ICF) and increase in short-interval intracortical inhibition (SICI) in the primary motor cortex (M1) contralateral to a cerebellar infarct. Our goal was to investigate intracortical M1 function in the chronic stage following cerebellar infarcts (> 4 months). We measured resting motor threshold (rMT), SICI, ICF, and ratios between motor-evoked potential amplitudes (MEP) and supramaximal M response amplitudes (MEP/M; %), after transcranial magnetic stimulation was applied to the M1 contralateral (M1(contralesional)) and ipsilateral (M1(ipsilesional)) to the cerebellar infarct in patients and to both M1s of healthy age-matched volunteers. SICI was decreased in M1(contralesional) compared to M1(ipsilesional) in the patient group in the absence of side-to-side differences in controls. There were no significant interhemispheric or between-group differences in rMT, ICF, or MEP/M (%). Our results document disinhibition of M1(contralesional) in the chronic phase after cerebellar stroke.

Alteration of cortical excitability in patients with fibromyalgia

We assessed cortical excitability and intracortical modulation systematically, by transcranial magnetic stimulation (TMS) of the motor cortex, in patients with fibromyalgia. In total 46 female patients with fibromyalgia and 21 normal female subjects, matched for age, were included in this study. TMS was applied to the hand motor area of both hemispheres and motor evoked potentials (MEPs) were recorded for the first interosseous muscle of the contralateral hand. Single-pulse stimulation was used for measurements of the rest motor threshold (RMT) and suprathreshold MEP. Paired-pulse stimulation was used to assess short intracortical inhibition (SICI) and intracortical facilitation (ICF). Putative correlations were sought between changes in electrophysiological parameters and major clinical features of fibromyalgia, such as pain, fatigue, anxiety, depression and catastrophizing. The RMT on both sides was significantly increased in patients with fibromyalgia and suprathreshold MEP was significantly decreased bilaterally. However, these alterations, suggesting a global decrease in corticospinal excitability, were not correlated with clinical features. Patients with fibromyalgia also had lower ICF and SICI on both sides, than controls, these lower values being correlated with fatigue, catastrophizing and depression. These neurophysiological alterations were not linked to medication, as similar changes were observed in patients with or without psychotropic treatment. In conclusion, fibromyalgia is associated with deficits in intracortical modulation involving both GABAergic and glutamatergic mechanisms, possibly related to certain aspects of the pathophysiology of this chronic pain syndrome. Our data add to the growing body of evidence for objective and quantifiable changes in brain function in fibromyalgia. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Impaired interhemispheric interactions in patients with major depression

Previous studies have shown that patients with major depression have an interhemispheric imbalance between right and left prefrontal and motor cortex. We aimed to investigate the interhemispheric interactions in patients with major depression using repetitive transcranial magnetic stimulation (rTMS). Thirteen patients with major depression and 14 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS (applied to the left primary motor cortex) was assessed in the left and right motor cortex and these results were compared with those in healthy subjects. There was a significant difference in the interhemispheric effects between patients with depression and healthy subjects. In healthy subjects, 1 Hz rTMS significantly decreased corticospinal excitability in the stimulated, left hemisphere and increased it in the contralateral, right hemisphere. In depressed subjects, 1 Hz rTMS also decreased corticospinal excitability in the left hemisphere; however, it induced no significant changes in corticospinal excitability in the contralateral, right hemisphere. In addition, there was a significant correlation between the degree of interhemispheric modulation and the severity of the depression as indexed by the Beck Depression Inventory scores. Our findings showing a decreased interhemispheric modulation in patients with major depression are consistent with the notion that mood disorders are associated with slow interhemispheric switching mechanisms.

Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

Changes in muscle recruitment patterns during skill acquisition

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, ill which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMC) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. Tn the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. Tn contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.

Neural adaptations to resistance training - Implications for movement control

It has long been believed that resistance training is accompanied by changes within the nervous system that play an important role in the development of strength. Many elements of the nervous system exhibit the potential for adaptation in response to resistance training, including supraspinal centres, descending neural tracts, spinal circuitry and the motor end plate connections between motoneurons and muscle fibres. Yet the specific sites of adaptation along the neuraxis have seldom been identified experimentally, and much of the evidence for neural adaptations following resistance training remains indirect. As a consequence of this current lack of knowledge, there exists uncertainty regarding the manner in which resistance training impacts upon the control and execution of functional movements. We aim to demonstrate that resistance training is likely to cause adaptations to many neural elements that are involved in the control of movement, and is therefore likely to affect movement execution during a wide range of tasks. We review a small number of experiments that provide evidence that resistance training affects the way in which muscles that have been engaged during training are recruited during related movement tasks. The concepts addressed in this article represent an important new approach to research on the effects of resistance training. They are also of considerable practical importance, since most individuals perform resistance training in the expectation that it will enhance their performance in-related functional tasks.

Binocular rivalry and the cerebral hemispheres with a note on the correlates and constitution of visual consciousness

In addressing the scientific study of consciousness, Crick and Koch state, "It is probable that at any moment some active neuronal processes in your head correlate with consciousness, while others do not: what is the difference between them?" (1998, p. 97). Evidence from electrophysiological and brain-imaging studies of binocular rivalry supports the premise of this statement and answers to some extent, the question posed. I discuss these recent developments and outline the rationale and experimental evidence for the interhemispheric switch hypothesis of perceptual rivalry. According to this model, the perceptual alternations of rivalry reflect hemispheric alternations, suggesting that visual consciousness of rivalling stimuli may be unihemispheric at any one time (Miller et al., 2000). However, in this paper, I suggest that interhemispheric switching could involve alternating unihemispheric attentional selection of neuronal processes for access to visual consciousness. On this view, visual consciousness during rivalry could be bihemispheric because the processes constitutive of attentional selection may be distinct from those constitutive of visual consciousness. This is a special case of the important distinction between the neuronal correlates and constitution of visual consciousness.

Coordination and movement pathology: models of structure and function

Here we consider the role of abstract models in advancing our understanding of movement pathology. Models of movement coordination and control provide the frameworks necessary for the design and interpretation of studies of acquired and developmental disorders. These models do not however provide the resolution necessary to reveal the nature of the functional impairments that characterise specific movement pathologies. In addition, they do not provide a mapping between the structural bases of various pathologies and the associated disorders of movement. Current and prospective approaches to the study and treatment of movement disorders are discussed. It is argued that the appreciation of structure-function relationships, to which these approaches give rise, represents a challenge to current models of interlimb coordination, and a stimulus for their continued development. (C) 2002 Elsevier Science B.V. All rights reserved.

Quantification of the TMS-EEG response in epilepsy

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica