Project

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Neural basis of praxis production: From higher-order processing to fine motor control

Applicant Bohlhalter Stephan
Number 129668
Funding scheme Project funding (Div. I-III)
Research institution Kantonsspital Luzern Medizinische Klinik
Institution of higher education Luzerner Kantonsspital - LUKS
Main discipline Clinical Pathophysiology
Start/End 01.08.2010 - 31.01.2014
Approved amount 328'089.00
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All Disciplines (3)

Discipline
Clinical Pathophysiology
Pathophysiology
Neurophysiology and Brain Research

Keywords (8)

Apraxia; Parkinson; pantomime; TMS; gesture; dexterity; imitation; rTMS

Lay Summary (English)

Lead
Lay summary
Aims of the research projectThe present project aims to explore the brain localization of skilled movements using so called repetitive transcranial magnetic stimulation (rTMS). Two types of skilled movements are of interest: gestures and fine motor skill. rTMS allows to transiently disturbing local brain function and therefore serves as a tool to study the role of distinct brain areas for motor control. For instance, it has been suggested that if gestures are performed on verbal command (pantomime domain) anterior brain regions seem to be mainly involved, whereas if copied on seen gestures (imitation domain) posterior areas play a stronger role. Fine motor skill is thought to be controlled by brain areas preceding those responsible for motor output. The goal of the present project is twofold: First, to assess in healthy subjects the influence of rTMS, applied over anterior and posterior brain sites, on gesture performance. Second, to study in patients with Parkinson's disease (PD) the effect of rTMS on dextrous finger movements that are frequently impaired in these patients. Context and significance of the project Gestures represent a body language and play a major role in nonverbal communication, for instance, pretending an object use when asking for a tool in a noisy environment. Gestures may compensate for communication problems in patients with stroke and language disturbance. However, gestures are frequently affected as well, thereby impeding rehabilitation of language deficits using gestural communication. Therefore, it is expected from the project that clarifying the role of distinct brain areas underlying gesturing may ultimately pave the way for more targeted treatments. Similarly, identification of brain areas controlling precise and independent finger movements may herald better therapeutic options for impaired fine motor skill in Parkinson's disease, which is often poorly amenable to current medical treatment. Scientific framework and methods usedThe first part of the project relates to gestures and will be conducted in healthy subjects. Effects of rTMS will be investigated using a test of upper limb apraxia (TULIA) covering 48 gestures in both domains. The second part focuses on the influence of rTMS on dextrous finger movements in PD as measured by the so called coin rotation (CR) task. In the CR task patients will be requested to rotate a coin (50 Rappen) as rapid as possible between their thumb, index and third finger. A new protocol of rTMS will be applied whose effect outlasts the actual stimulation (45 seconds) for at least 30 minutes. Motor assessments will be performed 5 minutes after rTMS stimulation has ended.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Interference with gesture production by theta burst stimulation over left inferior frontal cortex.
Bohlhalter Stephan, Vanbellingen Tim, Bertschi Manuel, Wurtz Pascal, Cazzoli Dario, Nyffeler Thomas, Hess Christian W, Müri René (2011), Interference with gesture production by theta burst stimulation over left inferior frontal cortex., in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiol, 122(6), 1197-202.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ESN Meeting Poster Left posterior parietal theta burst stimulation affects gestural imitation regardless of semantic content. 07.09.2012 Basel, Switzerland Vanbellingen Tim; Hess Christian; Bohlhalter Stephan; Müri René; Kaelin Alain; Bertschi Manuel;
SNG Meeting, Preis für bestes Poster erhalten Poster Left posterior parietal theta burst stimulation affects gestural imitation regardless of semantic content. 03.05.2012 Lugano, Switzerland Vanbellingen Tim; Bertschi Manuel; Bohlhalter Stephan; Kaelin Alain; Müri René; Hess Christian;


Awards

Title Year
Déjerine Dubois Preis 2012

Associated projects

Number Title Start Funding scheme
155954 Interference with gesture control and transcallosal white matter integrity: A theta-burst stimulation and diffusion tensor imaging study in apraxia after stroke 01.05.2015 Project funding (Div. I-III)
152619 Gesture deficits in Schizophrenia: A combined functional MRI and diffusion tensor imaging study of disconnectivity to investigate the neural basis of limb praxis 01.06.2014 Project funding (Div. I-III)

Abstract

1. Summary of Research PlanBackground and aim of the project Praxis production may be viewed as a hierarchical process involving recruitment of supramodal time-space representations (engrams) of skilled movements and their translation into proper gesture output by so called innervatory patterns. Recent neuroimaging studies in patients with apraxia suggest that pantomime and gesture recognition, both critically relying on stored motor engrams, involve mainly ventral premotor area (PMv), while imitation engages predominantly inferior parietal lobule (IPL). These findings challenge the traditional view on the essential role of parietal cortex in gesture representation. Parietal storage of engrams has been proposed since lesion of IPL predominantly affects the imitation of transitive (tool-related) acts that requires learned knowledge of object use. By contrast, damage to superior parietal lobule (SPL) disables rather meaningless gestures, which have to be calculated de novo each time they are produced. Loss of precise and independent finger movements, called limb kinetic apraxia, is thought to be caused by disrupted innervatory patterns putatively stored in premotor cortex. Manual dexterity is often impaired in Parkinson’s disease (PD) and in contrast to cardinal motor symptoms such as bradykinesia only little responsive to dopaminergic treatment. The neural basis for this discrepancy may be explained by basal ganglia-thalamo-cortical projections, which are much weaker to dorsal premotor areas (PMd) than to supplementary motor area (SMA). Therefore, PMd may represent a key localization for innervatory patterns underlying fine motor control. Neuroimaging data suggest that PMd function alters only in advanced PD, while SMA hypoactivation underlying bradykinesia is present early. The aim of the project is to study the neural basis of praxis production, both at the level of higher-order processing in healthy subjects and fine motor control in PD patients. We will use repetitive transcranial magnetic stimulation (rTMS) technique to interfere with various frontal and parietal areas considered to be involved. Working hypothesisBased on the current state of research we hypothesize that inhibition of left PMv by rTMS decreases scores in pantomiming gestures, as assessed by a test for upper limb apraxia (TULIA) and impairs gesture recognition in a modified version of a postural knowledge task (PKT). By contrast, inhibitory rTMS of IPL will interfere more with imitation than pantomime and recognition, whereas rTMS of PMd affects both domains equally but spares recognition. We predict that rTMS of IPL will particularly affect imitation of transitive and downregulation of SPL meaningless gestures. We further expect that modulation of PMd by rTMS, in contrast to dopaminergic stimulation, influences performance of coin rotation (CR) in advanced PD, supporting the premotor site of innervatory patterns. We finally conjecture that rTMS and dopaminergic response of CR will be less discrepant in early PD. Experimental design and methodsThe project has two main parts, comprising three and two experiments, respectively. The first part relates to higher-order praxis processing and will be conducted in healthy subjects (age range 18 to 45). Cognitive-motor effects of inhibitory rTMS in PMv versus IPL (first experiment), PMv versus PMd (second experiment) as well as IPL versus SPL (third experiment) will be investigated. We will use subscores of TULIA test and reaction times of modified PKT test as outcome measures. The TULIA test covers pantomime and imitation of transitive, intransitive and meaningless gestures. The PKT assesses gesture recognition by matching cartoons of transitive and intransitive acts with correct postures. The second part of the project focuses on limb kinetic praxis and will be performed in patients with PD, either in more advanced stage (fourth experiment), when wearing off fluctuations developed, or in de novo stage (fifth experiment) before dopaminergic treatment. Limb kinetic deficits can be straightforwardly assessed by the CR test. Bradykinesia will be measured by finger tapping task (FT). CR and FT scores will be the principal outcome measures. Behavioral measurements will be performed in an offline approach, that is, after TMS stimulation has ended. All TMS experiments will be sham controlled.Preliminary findings of a pilot experiment In right handed healthy subjects (n = 10) inhibitory rTMS over left PMv significantly suppressed gesture pantomiming when compared with stimulation over left IPL, while gesture imitation remained unchanged, pointing to an inferior frontal rather than inferior parietal gesture representation. The findings also suggest that inhibition of IPL favours the inferior frontal function during gesture pantomime. Significance of the project The present project addresses a major debate in current literature of apraxia, namely, the differential role of left inferior frontal and parietal cortex in gesture representation. Furthermore, elucidation of neural basis of various aspects of praxis processing may be relevant in restorative neurology by providing a more rationale basis for treatment strategies. Finally, identification of innervatory patterns may herald focal modulation by rTMS as therapeutic option for impaired dexterity in PD, which is poorly amenable to dopaminergic treatment.
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