H TMS διακρίνεται έναντι άλλων εργαλείων απεικόνισης λόγω της ικανότητάς της να ενεργοποιεί νευρώνες σε επιλεγμένες φλοιϊκές περιοχές. Η παρούσα μελέτη προσπαθεί να διερευνήσει το νευροφυσιολογικό προφίλ της μυικής προκλητής απάντησης διάμεσου διακρανιακής μαγνητικής διέγερσης (TMS) σε ένα σεβαστό αριθμό ασθενών με σχιζοφρένεια υπό φαρμακευτική αγωγή. Σε 51 ασθενείς υπό φαρμακευτική αγωγή και διάγνωση σχιζοφρένειας και 51 υγιείς μάρτυρες απόλυτα σύμφωνους ως προς το φύλο, το ύψος και την ηλικία με τους ασθενείς που συμμετείχαν καταγράφηκαν κινητικά προκλητά δυναμικά (ΜΕΡ) από τον απαγωγό μυ του αντίχειρα μετά τον ερεθισμό του αντίπλευρου κινητικού φλοιού με ένα κυκλικό πηνίο. Μετρήθηκαν: w RMTh (resting motor threshold): Ο ουδός κινητικής ηρεμίας w SI-max (stimulus intensity for maximum MEP): Η ένταση ερεθίσματος που χρειάζεται για την καταγραφή του μέγιστου κινητικού προκλητού δυναμικού w Post-stimulus silent period: Την ανερέθιστη περίοδο που επάγεται μετά από ένα ερέθισμα που προκαλεί συγκεκριμένη μυική δραστηριότητα w MEP Latency: Λανθάνον χρόνος των κινητικών προκλητών δυναμικών MEP amplitude: Το εύρος των κινητικών προκλητών δυναμικών. Τα βασικά ευρήματα είναι η σαφώς υψηλότερη από τις φυσιολογικές τιμές, τιμή των RMTh και SI-max και τα δύο, ενδείξεις νευρωνικής ευοδωτικής δραστηριότητας στους ασθενείς σε σύγκριση με τους μάρτυρες. Ειδικότερα στην ομάδα των ασθενών που βρίσκονται σε θεραπεία με ζιπρασιδόνη παρουσιάστηκε το υψηλότερο SI-max και στα δύο ημισφαίρια και το υψηλότερο RMTh στο αριστερό ημισφαίριο. Οι ασθενείς στην ομάδα που ελάμβαναν ολανζαπίνη παρουσίασαν το χαμηλότερο RMTh για το αριστερό ημισφαίριο και αυτοί σε θεραπεία με κουατιεπίινη παρουσίασαν τιμές ανάμεσα στις τιμές των δύο προηγούμενων ομάδων. Όταν χρησιμοποιήθηκε ένταση ερεθίσματος (SI) σχετικής τιμής με το RMTh, η ανερέθιστη περίοδος βρέθηκε μεγαλύτερη στους ασθενείς από ότι στους μάρτυρες ενώ δεν παρατηρήθηκε καμία διαφορά ανάμεσα στις δύο μεγάλες ομάδες ασθενών και μαρτύρων όταν χρησιμοποιήθηκε σταθερής έντασης ερέθισμα (SI). Συμπεράναμε, ότι οι αλλαγές στις παραμέτρους που μετρήθηκαν, μπορούν να εξηγηθούν από βασικές μεταβολές της ενδοφλοιϊκής ευοδωτικής κινητικής δραστηριότητας που ακολουθείται από διαφοροποιήσεις της φλοιϊκής αναστολής, οι οποίες μπορούν να αποδοθούν είτε στην σχιζοφρένεια είτε στην φαρμακευτική αγωγή ή στην αλληλεπίδρασή τους. / Trancranial magnetic stimulation (TMS) provides a non-invasive means for exploring physiological alterations of central motor control in a variety of neuropsychiatric diseases. The present study aimed to assess the neurophysiological profile of muscle evoked responses to a standard TMS procedure in a considerable number of medicated patients with schizophrenia. Fifty-one patients with diagnosis of schizophrenia and 51 sex- and age-matched healthy subjects were enrolled in the study. Motor evoked potential (MEP) from abductor pollicis brevis muscle was elicited by stimulation of the contralateral motor cortex with a circular coil. The hot-spot was marked. Were measured: ¨ the resting motor threshold (RMTh), ¨ the stimulus intensity for maximum MEP (SI-max), ¨ the post-stimulus silent period of voluntary muscle activity and ¨ MEP latency and amplitude. The main findings were the significantly higher than normal values for RMTh and SI-max, which are both indices of neuronal excitability. In particular, patients who had ziprasidone in their therapeutic regimen demonstrated the highest SI-max for both hemispheres and highest RMTh for left hemisphere, patients receiving olanzapine demonstrated the lowest RMTh for left hemisphere and those on quetiapine showed intermediate values. Silent period was longer in the patients as opposed to controls when a RMTh-related SI was used and did not differ between the two groups when a fixed SI was used. We concluded that the observed TMS changes could be interpreted by primary alterations of intracortical motor excitability followed by defects of cortical inhibition and should be attributed to schizophrenia, antipsychotic medication or the interaction between both factors.

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No description available.

INTRODUÇÃO: A dependência química engloba alterações comportamentais, cognitivas e fisiológicas. A impulsividade está presente em muitos transtornos psiquiátricos. Sobre a impulsividade na dependência química de cocaína, os estudos existentes são relativamente novos. A Estimulação Magnética Transcraniana de repetição (EMTr) é um método capaz de neuromodular o cérebro. Este estudo avaliou os efeitos da EMTr sobre a impulsividade em dependentes de cocaína. MÉTODOS: Em um estudo randomizado, duplamente encoberto, 25 pacientes diagnosticados pelo DSM-IV-TR foram tratados com EMTr de alta frequência ativa (1250 pulsos/dia) ou EMTr placebo. O tratamento consistiu em 1 mês de aplicação de EMTr seguido de 2 meses em acompanhamento ambulatorial semanal em um grupo de prevenção de recaídas. Os pacientes foram avaliados antes do início do tratamento com EMTr (T0) e após o término das aplicações (T1), através dos instrumentos: The Shorter PROMIS Questionnaire, The Schalling Impulsivity Scale e The Leeds Dependence Questionnaire. RESULTADOS: 25 pacientes foram tratados e a análise dos dados demonstraram redução nos índices de impulsividade em ambos os grupos ao longo do tempo, porém, quando comparados entre si, os valores de interação não se mostraram significativos. CONCLUSÃO: Os efeitos da EMTr não diferiram em eficácia terapêutica na redução da impulsividade em dependentes de cocaína, com o efeito ativo correspondendo com o placebo / INTRODUCTION: Chemical addiction involves behavioral, cognitive and physiological alterations. Impulsivity is present in many psychiatric disorders. Studies about impulsivity and cocaine chemical addiction are relatively new. Transcranial Magnetic Stimulation (EMTr) is a method capable of neuromodulation the brain. This study evaluated the effects of EMTr over impulsivity in cocaine addicts. METHODS: This is a randomized doubly covert study with 25 patients diagnosed by the DSM-IV-TR who were treated with active high frequency EMTr (1250 pulses/day) or placebo. Treatment was consisted of one month of application of EMTr followed by 2 months of clinical follow-up in a relapse prevention group. Patients were evaluated before the treatment with EMTr (T0) and after the end of the applications (T1), through the instruments: The Shorter PROMIS Questionnaire, The Schalling Impulsivity Scale and The Leeds Dependence Questionnaire. RESULTS: 25 patients were treated and data analysis showed a reduction in the levels of impulsivity in both groups throughout the time. However, group comparisons did not show statistical differences. CONCLUSION: EMTr\'s effects did not differ in terms of therapeutical efficacy in the reduction of impulsivity in cocaine addicts

Made available in DSpace on 2016-03-15T19:40:41Z (GMT). No. of bitstreams: 1 Rita dos Santos de Carvalho Picinini.pdf: 1897105 bytes, checksum: 40db215aab8bca0781df1d15de88b3d3 (MD5) Previous issue date: 2009-01-27 / Fundo Mackenzie de Pesquisa / Different mathematical skills have been investigated over time and, with the advance of neuroimaging techniques, such as PET (Positron Emission Tomography) and fMRI (functional Magnetic Resonance), central components of arithmetical processing have been identified in the parietal and the pre-frontal cortices. Besides the advances of the neuroimaging techniques, other techniques such as non-invasive brain modulation have also been studied such as the transcranial magnetic stimulation (TMS) and the transcranial direct current stimulation (TDCS) in the involvement of cognitive functions in the area of calculation. This study aimed at investigating the impact of anodal TDCS applied over the left dorsolateral pre-frontal cortex (LDLPFC), right parietal cortex (RPC), left parietal cortex (LPC) while the subject was performing multiplication operations. Fifteen healthy volunteers, students of psychology, aged between 18 and 30 years old, have held subtests of the WAIS III and the multiplication task. The results showed that the anodal TDCS over the RPC improved the performance of men regarding the number of rightness. The influence of TDCS on volunteers who had worse performance took place not on complex tasks, but simple arithmetical ones. Besides, the influence of TDCS on volunteers who had better performance was in complex tasks, not simple ones. These results show that the effects of the TDCS on a certain function depend on the baseline values of each volunteer. The other stimulation conditions over the LDLPFC and LPC did not show any significant results. The TDCS can bring a beneficial effect in calculation tasks, depending on the intensity, polarity, time and location of stimulation, resulting in the increased or diminished cortex excitability. / Diferentes habilidades matemáticas vêm sendo investigadas ao longo dos tempos e, com o avanço das técnicas de neuroimagem, como PET (Tomografia por emissão de Pósitrons) e fMRI (ressonância magnética funcional) componentes centrais no processamento aritmético vêm sendo identificados em córtex parietal e pré-frontal. Além do avanço das técnicas de neuroimagem, outras técnicas como de modulação cerebral não-invasiva também vêm sendo estudadas, como Estimulação Magnética Transcraniana (EMT) e a Estimulação Transcraniana por Corrente Contínua (ETCC) no envolvimento das funções cognitivas com a área de cálculo. Este estudo teve como objetivo investigar o impacto da ETCC anódica quando aplicada no Córtex Pré-Frontal Dorsolateral (CPFDLE), Córtex Parietal Direito (CPD), Córtex Parietal Esquerdo (CPE) no desempenho em operações de multiplicação. Quinze voluntários saudáveis, estudantes de psicologia, com faixa etária entre 18 e 30 anos, realizaram subtestes do WAIS III e a tarefa de multiplicação. Os resultados desse estudo mostraram que a ETCC anódica aplicada no CPD melhorou o desempenho dos homens em relação ao número de acertos. A influência da ETCC em participantes com pior desempenho em Aritmética se deu em tarefa simples de multiplicação, mas não complexa, ao passo que a influência da ETCC em participantes com melhor desempenho em Aritmética se deu em tarefa complexa de multiplicação, mas não em simples. Tais resultados sinalizam que os efeitos da estimulação em uma determinada função dependem dos valores de linha de base de cada participante As outras condições de estimulações, CPFDLE e CPE não resultaram em efeitos significativos. A ETCC pode produzir um efeito benéfico em tarefas de cálculo, dependendo da intensidade, polaridade, tempo e localização da estimulação, podendo resultar em aumento ou diminuição na excitabilidade do córtex.

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age.

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age.

Il existe différents facteurs pouvant altérer la récupération fonctionnelle de patients souffrant de traumatismes orthopédiques (TO), dont le fait de subir un traumatisme craniocérébral (TCC) concomitant. Le profil de traumatismes combinés (TCC et TO) a principalement été étudié en contexte de blessures jugées sévères (TCC modéré/sévère et multiples fractures), notamment dans un souci de maximiser la récupération de ces patients et le déploiement des ressources médicales. Par ailleurs, la littérature demeure limitée en ce qui a trait à l’impact de subir un TCC en contexte de blessures jugées moins sévères, soit un TCC léger (TCCL) et une fracture isolée (un seul os fracturé), bien qu’il s’agisse de deux blessures à très forte incidence et qu’elles partagent diverses similarités (p.ex. : mécanismes d’accidents et physiologiques communs). Ainsi, la présente thèse s’est spécifiquement intéressée à cette population aux prises avec une fracture isolée avec, ou sans, TCCL concomitant. Dans un premier temps, les travaux de la thèse ont permis d’investiguer la fréquence de TCCL concomitant en contexte de fracture isolée (article 1) ainsi que son impact sur la récupération post-fracture selon diverses mesures cliniques (articles 2, 3, 4). Les résultats ont démontré que le TCCL était fréquent, quoique fortement sous-diagnostiqué, chez des patients vus au département d’urgence (DU) pour une fracture isolée et que sa présence avait un impact significatif sur le niveau de douleur perçu, le délai pour retourner au travail et le risque de développer de l’ossification hétérotopique (forme de complications orthopédiques). Dans un deuxième temps, la présente thèse a utilisé une approche théorique (article 5) et clinique (article 6) afin d’étudier les mécanismes physiologiques sous-tendant la perception de douleur, symptôme clé suite à une fracture, dans un souci de limiter les risques de chronicisation de la douleur et de proposer des méthodes d’intervention ciblées selon la population étudiée. Les travaux ont notamment mis en lumière une association entre l’intensité de douleur rapportée par des patients en phase aiguë post-fracture et le degré d’atteintes des mécanismes d’excitabilité corticale du cortex moteur primaire mesurées par l’entremise de la stimulation magnétique transcranienne (SMT). Enfin, sur la base d’évidences théoriques soulevées dans un article de revue de la présente thèse, il semble y avoir une pertinence dans l’utilisation de la SMT auprès de la population orthopédique comme méthode d’investigation et d’intervention, considérant sa capacité à cibler les mécanismes physiologiques impliqués dans la transition de la douleur aiguë à la douleur chronique. / A variety of factors can affect the functional recovery of patients with an orthopedic trauma (OT), including concomitant traumatic brain injuries (TBI). The recovery profile of patients with combined traumas (OT and TBI) has been studied primarily in the context of severe injuries (moderate/severe TBI and multiple fractures), in order to maximize recovery and medical resources. On the other hand, there is limited evidence on the impact of concomitant TBI in the context of milder injuries, such as in patients sustaining a mild TBI combined with an isolated limb fracture, despite both injuries being highly prevalent and sharing various similarities (e.g., overlapping injury mechanisms and physiological mechanisms). The current thesis sought to bridge this knowledge gap via a multifaceted approach. We first investigated the risk of sustaining a concomitant mild TBI in patients with an isolated limb fracture (article 1) as well as its impact on post-fracture recovery according to various clinical measures (articles 2, 3, 4). The results showed that mild TBI was frequent, although highly underdiagnosed, in patients seeking care for an isolated limb fracture in the emergency department. Moreover, the presence of a concomitant mild TBI had a significant detrimental impact on the level of perceived pain, on return to work delays, and on the risks of developing heterotopic ossification (a type of orthopedic complication). Secondly, this thesis used a theoretical (article 5) and a clinical (article 6) approach to study the physiological mechanisms underlying pain perception, a key symptom following a fracture, in order to limit the risks for pain chronification and to propose intervention methods tailored to the studied population. In particular, results highlighted an association between pain intensity as perceived by patients in the acute phase post-fracture and the degree of cortical excitability impairments of the primary motor cortex, as measured by transcranial magnetic stimulation (TMS). Finally, based on theoretical evidence highlighted in a review article included in this thesis, there are evidence supporting the use of TMS in a traumatically injured population as a method to investigate and intervene given its ability to target key physiological mechanisms involved in the transition from acute to chronic pain.

Die transkranielle Magnetstimulation (TMS) ist ein nichtinvasives Hirnstimulationsverfahren, mit welchem sowohl die funktionelle Untersuchung umschriebener kortikaler Regionen als auch die Modulation der Erregbarkeit ebendieser sowie die Induktion neuroplastischer Phänomene möglich ist. Sie wurde in der Vergangenheit insbesondere bei der Erforschung des humanen zentralmotorischen Systems angewandt. Dabei zeigte sich, dass ein einzelner über dem primärmotorischen Areal (M1) applizierter TMS-Puls multiple deszendierende Erregungswellen im Kortikospinaltrakt induzieren kann. Von diesen Undulationen besitzt die D-Welle (direkte Welle) die kürzeste Latenz und sie rekurriert auf eine direkte Aktivierung kortikospinaler Neurone, wohingegen I-Wellen (indirekte Wellen) längere Latenzen besitzen und durch transsynaptische Aktivierung dieser Zellen entstehen. Bemerkenswert ist das periodische Auftreten der letztgenannten Erregungswellen mit einer Periodendauer von etwa 1,5 ms. Zwar sind die genauen Mechanismen noch unbekannt, welche der Entstehung dieser I-Wellen sowie dem Phänomen der I-Wellen-Fazilitierung, das sich in geeigneten TMS-Doppelpulsprotokollen offenbart, zugrunde liegen, jedoch existieren hierzu verschiedene Erklärungsmodelle. Im Mittelpunkt der vorliegenden Arbeit steht die repetitive Anwendung eines TMS-Doppelpulsprotokolls, bei dem das Interpulsintervall (IPI) im Bereich der I-Wellen-Periodizität liegt (iTMS) und das gleichsam durch eine Implementierung der I-Wellen-Fazilitierung in der repetitiven TMS charakterisiert ist. Da gezeigt werden konnte, dass iTMS mit einem IPI von 1,5 ms (iTMS_1,5ms) die kortikospinale Erregbarkeit signifikant intra- und postinterventionell zu steigern vermag, und die I-Wellen-Periodizität interindividuellen Schwankungen unterliegt, wurde in der hier vorgestellten Studie an Normalprobanden der Einfluss einer individuellen Anpassung des IPIs (resultierend in der iTMS_adj) auf die intrainterventionelle kortikospinale Erregbarkeit untersucht. In der Tat stellte sich heraus, dass die iTMS_adj der iTMS_1,5ms diesbezüglich überlegen ist. Dieses Ergebnis unterstreicht das Potential einer Individualisierung der interventionellen TMS für erregbarkeitsmodulierende Effekte und macht dasjenige der ohnehin auf physiologische Prozesse abgestimmten iTMS explizit, was insbesondere für klinische Anwendungen relevant sein mag.

Il existe des projections corticospinales (CS) vers les motoneurones (MNs) aussi bien contra- (c) qu’ipsilatérales (i). Les influences CSc sur les MNs du poignet sont connues pour être modulées entre autres par la position du poignet et les afférences cutanées. Pour cette raison, notre objectif était de vérifier si ces caractéristiques sont aussi valides pour les influences CSi. En utilisant la stimulation transcrânienne magnétique au niveau du cortex primaire droit, nous avons tout d’abord comparé les influences CSi sur les MNs des fléchisseurs du poignet à des positions maintenues de flexion et d’extension durant une tâche uni-manuelle ainsi que deux tâches bimanuelles, ceci chez des sujets droitiers (n=23). Nous avons ensuite comparé les influences CSi dans cinq tâches bi-manuelles de tenue d’objet durant lesquelles les sujets avaient à tenir entre leurs mains un bloc à la surface soit lisse, soit rugueuse, dont le poids était supporté ou non, ceci en position de flexion (n=21). Dans une tâche, un poids était ajouté au bloc lisse en condition non supportée pour amplifier les forces de préhension requises. Une modulation positiondépendante était observée au niveau des potentiels évoqués moteurs (iPEM), mais seulement lors de la tâche bi-manuelle quand les deux mains interagissaient via un bloc (p= 0.01). Une modulation basée sur la texture était également présente, quel que soit le support de poids, et le bloc lisse était associé avec des iPEMs plus importants en comparaison avec le bloc rugueux (p= 0.001). Ainsi, les influences CSi sur les MNs n’étaient modulées que lors des tâches bi-manuelles et dépendaient de la manière dont les mains interagissaient. De plus, les afférences cutanées modulaient les influences CSi facilitatrices et pourraient ainsi participer à la prise en main des objets. Il en est conclu que les hémisphères droit et gauche coopèrent durant les tâches bimanuelles impliquant la tenue d’objet entre les mains, avec la participation potentielle de projections mono-, et poly-synaptiques, transcallosales inclues. La possibilité de la contribution de reflexes cutanés et d’étirement (spinaux et transcorticaux) est discutée sur la base de la notion que tout mouvement découle du contrôle indirect, de la « référence » (referent control). Ces résultats pourraient être essentiels à la compréhension du rôle des interactions interhémisphériques chez les sujets sains et cliniques. / There are both contra- (c) and ipsilateral (i) corticospinal (CS) projections to motoneurons (MNs). There is evidence that cCS influences on wrist MNs are modulated by wrist position and cutaneous afferents. Thus, we aimed to test whether these findings are valid for iCS influences as well. Using transcranial magnetic stimulation applied over the right primary motor cortex, we first compared iCS influences on wrist flexor MNs at actively maintained flexion and extension wrist positions in one uni- and two bimanual tasks in right-handed subjects (n=23). We further compared iCS influences in five bimanual holding tasks in which subjects had to hold a smooth or coarse block between their hands, with or without its weight being supported, in flexion position (n=21). In one task, a weight was added to the unsupported smooth block to increase load forces. A position-dependent modulation of the short-latency motor evoked potential (iMEP) was observed, but only in the bimanual task when the two hands interacted through a block (p=0.01). A texture-dependent modulation was present regardless of the weight supported, and the smooth block was associated with larger iMEPs in comparison to the coarse block (p=0.001). Hence, iCS influences on MNs were modulated only in bimanual tasks and depended on how the two hands interacted. Furthermore, cutaneous afferents modulated facilitatory iCS influences and thus may participate to grip forces scaling and maintaining. It is concluded that the left and right cortices cooperate in bimanual tasks involving holding an object between the hands, with possible participation of mono- and poly-synaptic, including transcallosal projections to MNs. The possible involvement of spinal and trans-cortical stretch and cutaneous reflexes in bimanual tasks when holding an object is discussed based on the notion that indirect, referent control underlies motor actions. Results might be essential for the understanding of the role of intercortical interaction in healthy and neurological subjects.