Biomedical subjects

Tomás Paus

Publications and source records attributed to Tomás Paus.

At least 19 recordsLinked to original sources

PubMed2006

The neural response to transcranial magnetic stimulation of the human motor cortex. II. Thalamocortical contributions.

Beta oscillations (15-30 Hz) constitute an important electrophysiological signal recorded in the resting state over the human precentral gyrus. The brain circuitry involved in generating the beta oscillations is not well understood but appears to involve both cortical and subcortical structures. We have shown that single pulses of transcranial magnetic stimulation (TMS) applied over the primary motor cortex consistently elicit a brief beta oscillation. Reducing the local cortical excitability using low-frequency repetitive TMS does not change the amplitude of the induced beta oscillation (Van Der Werf and Paus in Exp Brain Res DOI 10.1007/s00221-006-0551-2). Here, we investigated the possible involvement of the thalamus in the cortically expressed beta response to single-pulse TMS. We included eight patients with Parkinson's disease who had undergone unilateral surgical lesioning of the ventrolateral nucleus of the thalamus. We administered 50 single pulses of TMS, at an intensity of 120% of resting motor threshold, over the left and right primary motor cortex and, at the same time, recorded the electroencephalogram (EEG) using a 60-electrode cap. We were able to perform analyses on seven EEG data sets and found that stimulation of the unoperated hemisphere (with thalamus) resulted in higher amplitudes of the single-trial induced beta oscillations than in the operated hemisphere (with thalamotomy). The beta oscillation obtained in response to pulses applied over the unoperated hemisphere was also higher than that obtained in healthy controls. We suggest that (1) the beta oscillatory response to pulses of TMS applied over the primary motor cortex is higher in Parkinson's disease patients, (2) thalamotomy serves to reduce the abnormally high TMS-induced beta oscillations, and (3) the motor thalamus facilitates the cortically generated oscillation, through cortico-subcortico-cortical feedback loops.

Aged↗

PubMed2006

Changes in effective connectivity of the primary motor cortex in stroke patients after rehabilitative therapy.

We used a perturb-and-measure approach, by combining transcranial magnetic stimulation (TMS) and positron emission tomography (PET), to examine changes in the primary motor area (M1) and its effective connectivity in stroke patients with chronic motor deficits (>1-year post-stroke) who underwent 3 weeks of constraint-induced movement therapy. During the 3-week period, 7 patients spent 4 h per day performing shaping exercises with the affected arm under our supervision for 14 days and wore a mitt on the unaffected arm at home in situations where safety was not compromised. Anatomical magnetic resonance imaging confirmed that all patients had lesions that encompassed the white matter; no patient had damage in the hand representation of M1. Improvements on various motor tests were observed immediately after therapy and 1 month afterwards. During the TMS/PET sessions, we applied trains of subthreshold 10-Hz repetitive TMS over the hand representation of the ipsilesional and contralesional M1s and varied the number of TMS trains delivered during each scan. The results demonstrate changes in the local response of TMS in the ipsilesional and contralesional M1, changes in the strength of interhemispheric connectivity between M1s, and changes in the effective connectivity of the ipsilesional and contralesional M1s with the non-primary motor areas, the basal ganglia, and the motor nuclei of the thalamus.

Aged↗

PubMed2006

The neural response to transcranial magnetic stimulation of the human motor cortex. I. Intracortical and cortico-cortical contributions.

We investigated the properties of the neural response to transcranial magnetic stimulation (TMS) applied over the human primary motor cortex. Consistent with our previous findings, single pulses of TMS induce a characteristic negative deflection at 45 ms (N45) and a transient oscillation in the beta frequency-range (15-30 Hz), as measured using electroencephalograpy (EEG). Here we show the relative specificity of the beta oscillation and the N45; both are stronger when elicited by stimulation applied over the primary motor cortex, as compared with stimulation over the dorsal premotor cortex. We also provide a quantitative analysis of the beta responses to single pulses of TMS and show that the responses are highly phaselocked to the TMS pulses within single subjects; this phaselocking is similar from subject to subject. A single pulse of TMS applied over the primary motor cortex thus appears to reset the ongoing oscillations of the neurons, bringing them transiently into synchrony. Finally, we examine the effect of local or distal modulation of the excitability of the primary motor cortex on the beta oscillation and the N45 in response to single-pulse TMS. We applied low-frequency subthreshold repetitive TMS either over the primary motor cortex (local modulation) or, on a separate day, over the dorsal premotor cortex (distal modulation). The modulation was evaluated with single suprathreshold test pulses of TMS applied over the primary motor cortex before and after the subthreshold low-frequency rTMS. We recorded the EEG response throughout the testing session, i.e. to both the subthreshold and the suprathreshold pulses. After repetitive TMS applied over the primary motor cortex, but not the dorsal premotor cortex, the amplitude of the N45 in response to suprathreshold pulses tended to decrease (not significant), and subsequently increased (significant); neither type of repetitive TMS affected the amplitude of the beta oscillation. We conclude that (1) the N45 depends on circuits intrinsic to the primary motor cortex; (2) the beta oscillation is specific to stimulation of the primary motor cortex, but is not affected by modulation of either cortical area and; (3) the beta oscillatory response to pulses of TMS arises from resetting of ongoing oscillations rather than their induction.

Adult↗

PubMed2006

Transcranial magnetic stimulation of frontal oculomotor regions during smooth pursuit.

Both the frontal eye fields (FEFs) and supplementary eye fields (SEFs) are known to be involved in smooth pursuit eye movements. It has been shown recently that stimulation of the smooth-pursuit area of the FEF [frontal pursuit area (FPA)] in monkey increases the pursuit response to unexpected changes in target motion during pursuit. In the current study, we applied transcranial magnetic stimulation (TMS) to the FPA and SEF in humans during sinusoidal pursuit to assess its effects on the pursuit response to predictable, rather than unexpected, changes in target motion. For the FPA, we found that TMS applied immediately before the target reversed direction increased eye velocity in the new direction, whereas TMS applied in mid-cycle, immediately before the target began to slow, decreased eye velocity. For the SEF, TMS applied at target reversal increased eye velocity in the new direction but had no effect on eye velocity when applied at mid-cycle. TMS of the control region (leg region of the somatosensory cortex) did not affect eye velocity at either point. Previous stimulation studies of FPA during pursuit have suggested that this region is involved in controlling the gain of the transformation of visual signals into pursuit motor commands. The current results suggest that the gain of the transformation of predictive signals into motor commands is also controlled by the FPA. The effect of stimulation of the SEF is distinct from that of the FPA and suggests that its role in sinusoidal pursuit is primarily at the target direction reversal.

Adult↗

PubMed2006

The primary motor and premotor areas of the human cerebral cortex.

Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

Animals↗

PubMed2005

Modulation of phosphene perception during saccadic eye movements: a transcranial magnetic stimulation study of the human visual cortex.

Saccadic suppression allows for perceptual stability during rapid movements of the eyes. One of the neural mechanisms may involve saccade-related modulation of neural activity in the visual cortex. Using the perception of phosphenes induced by transcranial magnetic stimulation (TMS) applied over the visual cortex (VC) as an index of cortical excitability, we sought to determine if VC excitability was modulated at varying times relative to saccade onset. We used two measures of excitability: (1) stimulator intensity required to induce phosphenes in 50% of trials, also called the phosphene threshold (PT), and (2) the subjective intensity of the phosphene. We found that there was no change in PT for different saccade-TMS onset asynchronies while there was an increase in perceived phosphene-intensity near the time of saccade onset (F(7,42) = 4.34, P = 0.001). Contrary to what would be expected from a saccadic suppression model, our results suggest that excitability of the visual cortex is slightly enhanced at the time of saccade onset.

Adult↗

PubMed2005

Brain networks involved in viewing angry hands or faces.

Most neuropsychological research on the perception of emotion concerns the perception of faces. Yet in everyday life, hand actions are also modulated by our affective state, revealing it, in turn, to the observer. We used functional magnetic resonance imaging (fMRI) to identify brain regions engaged during the observation of hand actions performed either in a neutral or an angry way. We also asked whether these are the same regions as those involved in perceiving expressive faces. During the passive observation of emotionally neutral hand movements, the fMRI signal increased significantly in dorsal and ventral premotor cortices, with the exact location of the 'peaks' distinct from those induced by face observation. Various areas in the extrastriate visual cortex were also engaged, overlapping with the face-related activity. When the observed hand action was performed with emotion, additional regions were recruited including the right dorsal premotor, the right medial prefrontal cortex, the left anterior insula and a region in the rostral part of the supramarginal gyrus bilaterally. These regions, except for the supramarginal gyrus, were also activated during the perception of angry faces. These results complement the wealth of studies on the perception of affect from faces and provide further insights into the processes involved in the perception of others underlying, perhaps, social constructs such as empathy.

Adult↗

PubMed2005

Inferring causality in brain images: a perturbation approach.

When engaged by a stimulus, different nodes of a neural circuit respond in a coordinated fashion. We often ask whether there is a cause and effect in such interregional interactions. This paper proposes that we can infer causality in functional connectivity by employing a 'perturb and measure' approach. In the human brain, this has been achieved by combining transcranial magnetic stimulation (TMS) with positron emission tomography (PET), functional magnetic resonance imaging or electroencephalography. Here, I will illustrate this approach by reviewing some of our TMS/PET work, and will conclude by discussing a few methodological and theoretical challenges facing those studying neural connectivity using a perturbation.

Brain Mapping↗

PubMed2005

Role of the primary motor and dorsal premotor cortices in the anticipation of forces during object lifting.

When lifting small objects, people apply forces that match the expected weight of the object. This expectation relies in part on information acquired during a previous lift and on associating a certain weight with a particular object. Our study examined the role of the primary motor and dorsal premotor cortices in predicting weight based either on information acquired during a previous lift (no-cue experiment) or on arbitrary color cues associated with a particular weight (cue experiment). In the two experiments, subjects used precision grip to lift two different weights in a series of trials both before and after we applied low-frequency repetitive transcranial magnetic stimulation over the primary motor and dorsal premotor cortices. In the no-cue experiment, subjects did not receive any previous information about which of two weights they would have to lift. In the cue experiment, a color cue provided information about which of the two weights subjects would have to lift. Our results demonstrate a double dissociation in the effects induced by repetitive stimulation. When applied over the primary motor cortex, repetitive stimulation disrupted the scaling of forces based on information acquired during a previous lift. In contrast, when applied over the dorsal premotor cortex, repetitive stimulation disrupted the scaling of forces based on arbitrary color cues. We conclude that the primary motor and dorsal premotor cortices have unique roles during the anticipatory scaling of forces associated with the lifting of different weights.

Adult↗

PubMed2005

Cortical regions involved in eye movements, shifts of attention, and gaze perception.

Human vision is an active process that involves shifting attention across the visual scene, with or without moving the eyes. Such shifts of attention can be generated at will (endogenously) or be triggered automatically, i.e., generated in response to exogenous stimuli including socially relevant cues such as someone else's gaze. What are the common and distinct brain mechanisms involved in these processes? To address this question, we carried out a quantitative effect-location meta-analysis of 59 brain-imaging experiments whose results were published using standardized coordinates. For each condition of interest, namely voluntary and visually triggered eye movements, voluntary and visually triggered (covert) shifts of attention, and perception of someone else's gaze, we computed activation likelihood estimation (ALE) maps. Those maps represent at each voxel of the brain the probability of reporting a signal change related to the condition of interest. For eye movements, this analysis confirmed the spatial location of the frontal eye fields, supplementary eye fields, and parietal saccade-related regions. The map of covert shifts of attention demonstrated highest similarity with the map of saccadic eye movements. Gaze perception showed common activation likelihood with the other conditions in the right intraparietal sulcus and in the lateral precentral gyrus. It demonstrated more similarity with the reflexive than with the voluntary saccades and shifts of attention. We propose that a core network of frontoparietal and temporal brain regions is recruited when we shift the focus of our attention with or without eye movements in response to the appearance of a visual target, as well as when we see someone else shift his or her gaze.

Attention↗

PubMed2005

Mapping brain maturation and cognitive development during adolescence.

Non-invasive mapping of brain structure and function with magnetic resonance imaging (MRI) has opened up unprecedented opportunities for studying the neural substrates underlying cognitive development. There is an emerging consensus of a continuous increase throughout adolescence in the volume of white matter, both global and local. There is less agreement on the meaning of asynchronous age-related decreases in the volume of grey matter in different cortical regions; these might equally represent loss ("pruning") or gain (intra-cortical myelination) of tissue. Functional MRI studies have so far focused mostly on executive functions, such as working memory and behavioural inhibition, with very few addressing questions regarding the maturation of social cognition. Future directions for research in this area are discussed in the context of processing biological motion and matching perceptions and actions.

Adolescent↗

PubMed2005

Changes in white matter in long-term survivors of severe non-missile traumatic brain injury: a computational analysis of magnetic resonance images.

The aim of this study was to investigate long-term consequences of severe non-missile traumatic brain injury (nmTBI) in patients without macroscopic focal brain lesions (>1.6 cm(3)) on regional white-matter density (WMd), and possible correlations with days of coma and memory performances. T1-weighted magnetic-resonance images (MRI) were acquired in 19 nmTBI patients, 3-113 months following the injury, and in 19 control subjects matched for age and gender. In addition, nmTBI patients underwent a battery of standardised memory tests. The MRIs were processed in a fully automatic system using voxel-by-voxel methods. Corpus callosum, fornix, anterior limb of the internal capsule, superior frontal gyrus, para-hippocampal gyrus, optic radiation and chiasma showed significant WMd reduction in nmTBI when compared to control subjects. None of the correlations between days of coma and memory performance scores with nmTBI voxels value that showed WMd reduction reached significance, with the exception of a significant negative correlation between WMd in the mid body of corpus callosum and short-story delayed recall. We detected reductions in WM density in several brain locations similar to those described in previous post mortem investigations. In addition, we observed WMd reduction in the optic chiasma and in the optic radiations; this finding may reflect transneural degeneration along the visual pathway. The weak correlations between specific anatomical sites of the reduced WMd and behavior may reflect the diffuse nature of the brain damage and/or the different time of onset between behavioral manifestations and neuropathological modifications occurring in nmTBI.

Adolescent↗

PubMed2004

Stimulation of the posterior parietal cortex interferes with arm trajectory adjustments during the learning of new dynamics.

Substantial neurophysiological evidence points to the posterior parietal cortex (PPC) as playing a key role in the coordinate transformation necessary for visually guided reaching. Our goal was to examine the role of PPC in the context of learning new dynamics of arm movements. We assessed this possibility by stimulating PPC with transcranial magnetic stimulation (TMS) while subjects learned to make reaching movements with their right hand in a velocity-dependent force field. We reasoned that, if PPC is necessary to adjust the trajectory of the arm as it interacts with a novel mechanical system, interfering with the functioning of PPC would impair adaptation. Single pulses of TMS were applied over the left PPC 40 msec after the onset of movement during adaptation. As a control, another group of subjects was stimulated over the visual cortex. During early stages of learning, the magnitude of the error (measured as the deviation of the hand paths) was similar across groups. By the end of the learning period, however, error magnitudes decreased to baseline levels for controls but remained significantly larger for the group stimulated over PPC. Our findings are consistent with a role of PPC in the adjustment of motor commands necessary for adapting to a novel mechanical environment.

Adaptation, Physiological↗

PubMed2004

Mechanisms of action underlying the effect of repetitive transcranial magnetic stimulation on mood: behavioral and brain imaging studies.

In a set of experiments, we applied 10-Hz repetitive transcranial magnetic stimulation (rTMS) over the left mid-dorsolateral frontal cortex (MDLFC) to investigate rTMS-induced changes in affective state and neural activity in healthy volunteers. In Experiment 1, we combined 10-Hz rTMS with a speech task to examine rTMS-induced changes in paralinguistic aspects of speech production, an affect-relevant behavior strongly linked to the ACC. In Experiment 2, we combined 10-Hz rTMS with positron emission tomography (PET) and used partial least squares (PLS) to identify a pattern of brain regions whose connectivity with the site of stimulation varied as a function of rTMS. The results of Experiment 1 revealed that following stimulation of the left MDLFC, subjects reported having less positive affect and vitality and displayed more monotonous speech. In Experiment 2, results revealed that 10-Hz rTMS influenced the covariation between blood flow at the site of stimulation (ie the left MDLFC) and blood flow in a number of affect-relevant brain regions including the perigenual anterior cingulate gyrus, insula, thalamus, parahippocampal gyrus, and caudate nucleus. Taken together, our results suggest that changes in affect and affect-relevant behaviour following 10-Hz rTMS applied over the left MDLFC may be related to changes in neural activity in brain regions widely implicated in affective states, including a frontocingulate circuit.

Acoustic Stimulation↗

PubMed2004

The role of the anterior cingulate cortex in pitch variation during sad affect.

We examined neural activity, in the frontal lobes, associated with speech production during affective states. Using functional magnetic resonance imaging (fMRI), the blood oxygen level-dependent (BOLD) response to the overt reading of emotionally neutral sentences was measured before and after a happy or sad mood induction. There was no explicit demand to produce affect-congruent speech and a cover story was used to de-emphasize the significance of the speech task in light of our experimental aims. Each fMRI measurement was acquired 6 s after the onset of sentence presentation so that speech could be recorded while the scanner noise was minimal; speech parameters (e.g. pitch variation) were extracted from the sentences and regressed against fMRI data. In the sad group we found the predicted changes in affect and pitch variation. Further, the fMRI data confirmed our hypothesis in that the 'reading effect' (i.e. the BOLD response to reading minus the BOLD response to baseline stimuli) in the supracallosal anterior cingulate cortex covaried negatively with both pitch variation and affect. Our results suggest that the anterior cingulate cortex modulates paralinguistic features of speech during affective states, thus placing this neural structure at the interface between action and emotions.

Adult↗

PubMed2004

Effects of left inferior prefrontal stimulation on episodic memory formation: a two-stage fMRI-rTMS study.

Successful recovery of words from episodic memory relies strongly on semantic processes at the time of encoding. Evidence from several functional magnetic resonance imaging (fMRI) studies has shown that changes in neural activity in the left inferior prefrontal cortex (LIPFC) during semantic encoding predict subsequent memory performance. This evidence has been taken to suggest that LIPFC plays a critical role in memory formation. Functional neuroimaging findings, however, do not establish a causal brain-behavior relationship. To determine whether there is a causal link between LIPFC involvement at encoding and subsequent success in memory performance, we conducted a two-part study in which we first used fMRI to localize encoding-related activation in LIPFC and then employed repetitive transcranial magnetic stimulation (rTMS) to manipulate neural processes in LIPFC during semantic encoding. To demonstrate the neuroanatomical specificity of any observed effect and to control for nonspecific rTMS side effects, we also stimulated neural processes in two control sites. Using frameless stereotaxy, we positioned the stimulation coil to target (1) the LIPF region that was activated during fMRI (mean xyz = -48 35 5); (2) the homologous right-hemisphere region; and (3) an additional left parietal control site. At each site, "stimulated" items (600 msec of 7-Hz rTMS with Cadwell Round Coil) were intermixed with items presented without concurrent stimulation. Subsequently, subjects performed a recognition memory task for the words encountered. We found support for the predicted causal brain-behavior relationship, which was specific to LIPFC. When comparing recognition scores for stimulated items, normalized for variations in performance on nonstimulated trials, we found that words encoded under LIPFC stimulation were subsequently recognized with higher accuracy than words encoded under stimulation in the two cortical control sites. By contrast, no performance difference emerged when the two control sites were compared with each other. Based on additional analyses of the rTMS effects observed directly at the time of encoding (i.e., on semantic-decision performance), we suggest that LIPFC stimulation may have produced its effect on recognition memory, at least in part, through the triggering of more extensive processing of the stimulated items and an ensuing gain in item distinctiveness. Physiological processes of facilitation probably also contributed to the observed memory benefit. Together, these findings suggest that LIPFC does play a causal role in episodic memory formation.

Adolescent↗

PubMed2004

Transcranial magnetic stimulation (TMS) of the human frontal cortex: implications for repetitive TMS treatment of depression.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive tool used to manipulate activity in specific neural circuits of the human brain. Clinical studies suggest that, in some patients with major depression, rTMS has the potential to alleviate symptoms that may be related to functional abnormalities in a frontocingulate circuit. This paper reviews the rationale for the use of rTMS in this context. The following topics are discussed: symptoms and cognition in major depression, with special emphasis on the initiation of speech; neuroimaging studies of depression; rTMS as treatment for depression; structure and function of the mid-dorsolateral frontal and anterior cingulate cortices; and combined TMS/positron emission tomography studies of frontocortical connectivity.

Brain↗

PubMed2003

Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex.

Brain dopamine is implicated in the regulation of movement, attention, reward and learning. Dysfunction of dopamine plays a role in Parkinson's disease, schizophrenia and drug addiction. It is released in the striatum when dopamine neurons in the midbrain undergo burst firing. Several animal studies have shown that dopamine can also be released under direct control of glutamatergic corticostriatal efferents. However, the existence and physiological significance of this mode of action remain controversial. We have shown previously that repetitive transcranial magnetic stimulation (rTMS) of the human prefrontal cortex led to focal dopamine release in the ipsilateral caudate nucleus, supporting the corticostriatal mode of dopamine release. Using the same experimental approach, we sought to confirm this hypothesis. We used [11C]raclopride and PET to measure changes in extracellular dopamine concentration following rTMS of the motor cortex in six healthy human subjects. rTMS of the left primary motor cortex caused a reduction in [11C]raclopride binding in the left putamen compared with rTMS of the left occipital cortex. There were no changes in binding in the right putamen, caudate nucleus or nucleus accumbens. The area of statistically significant change in binding corresponded closely to the known projection zone of corticostriatal efferents originating in monkey motor cortex. This finding has implications for the functional role of subcortical dopamine.

Adult↗