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Bottom-up transfer of sensory-motor plasticity to recovery of spatial cognition: visuomotor adaptation and spatial neglect.

A large proportion of right-hemisphere stroke patients show hemispatial neglect, a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. This spatial cognition disorder affects the orientation of behavior with a shift of proprioceptive representations toward the lesion side. This shift is similar to that produced by psychophysical manipulations as a wedge-prism exposure in normal healthy subjects. In both subjects, one major compensative effect of short-term prism adaptation is a shift of proprioceptive representations, demonstrated by a shift in manual straight-ahead pointing in the dark, in a direction opposite to the visual shift. In neglect patients, prism adaptation involves the shift of proprioceptive representations to the left with a reduction of rightward bias observed in neglect patients in visuo-manual tasks as line-bisection, line-cancellation or copy drawing. Improvement of neglect is also observed in no visuo-manual tasks as mental imagery, auditory extinction or posture. This generalization of prism adaptation effects at different neglect level symptoms suggests that the process of prism adaptation may activate brain functions related to multisensory integration and higher spatial representations. Moreover the positive effects found for both sensorimotor and more cognitive spatial functions lasted for at least two or more hours after prism removal. Unlike reduction of neglect through sensory stimulations, the long-lasting improvement of neglect after prism adaptation suggests the activation of short-term plasticity of brain functions related to coordinate transformations and space representations. Lastly, the duration of these effects could be useful in rehabilitation programs, as suggested by the effects of prism adaptation on disabling neglect symptoms as wheelchair driving, posture or writing.

Adaptation, Physiological↗

Long-term consequences of switching handedness: a positron emission tomography study on handwriting in "converted" left-handers.

Until some decades ago, left-handed children who attended German schools were forced to learn to write with their right hand. To explore the long-term consequences of switching handedness, we studied the functional neuroanatomy of handwriting in 11 adult "converted" left-handers and 11 age-matched right-handers. All participants had used exclusively their right hand for writing since early childhood. Using [15O]H2O positron emission tomography, changes in normalized regional cerebral blood flow (rCBF) were assessed while participants repetitively wrote a stereotyped word with their right hand. The kinematics of handwriting did not differ between converted left-handers and right-handers. In innate right-handers, handwriting caused a preponderant left-hemispheric activation of parietal and premotor association areas. In contrast, converted left-handers demonstrated a more bilateral activation pattern with distinct activation foci in the right lateral premotor, parietal, and temporal cortex. Moreover, foci in the right rostral supplementary motor area and the right inferior parietal lobule demonstrated a positive linear relationship between the degree of "left-handedness" and normalized rCBF during right-hand writing. Functional activity in the primary sensorimotor cortex was not affected by handedness. Our findings provide evidence for persisting differences in the functional neuroanatomy of handwriting between right-handers and converted left-handers, despite decades of right-hand writing. Right-hemispheric activation in converted left-handers may reflect suppression of unwanted left-hand movements. Alternatively, this activity may represent persistent left-handedness and, as such, demonstrate a hemispheric asymmetry of hand movement representations in cortical motor association areas in relation to the direction and degree of handedness.

Acoustic Stimulation↗

Effect of developmental sensory and motor deprivation on the functional organization of adult rat somatosensory cortex.

Most sensory systems are active, in the sense that the animal performs specific motor actions in order to collect information of interest-signals are not merely passively received. We, therefore, expect cortical development to depend not only correct sensory experience, but also on correct motor experience. In this study, we used the rat whisker system as a model to compare the importance of these factors. In one group of animals, we trimmed all whiskers starting from post-natal day 8 (P8). In a second group, we left the whiskers intact, but prevented "whisking" by sectioning the facial (VIIth cranial) nerve on P8. The first group had severely disrupted sensory experience but normal motor patterns ("whisker-cut" rats); the second group had normal sensory pathways within which temporal activity patterns were disrupted by motor impairment ("nerve-cut" rats). When they reached 3 months of age, we recorded multi-unit responses from the infragranular layers of primary somatosensory cortex in response to deflection of either single whiskers or pairs of whiskers in order to compare these two groups to a third group of rats that had normal sensory and motor experience. Cortical topographic organization was unaltered in whisker- and nerve-cut rats. Whisker-cut rats showed a smaller than normal difference between the response magnitudes for the principal and surrounding whiskers, as well as stronger than normal interactions between co-active whisker inputs. Responses in nerve-cut rats were nearly indistinguishable from those in normal animals. Thus, unexpectedly, neither pure sensory nor sensorimotor deprivation caused gross functional disruption of SI according to our measures. It appears that abnormal sensory experience leads to alterations in the fine-tuning of cortical properties, but cortex is unexpectedly resistant to the effects of abnormal sensory and sensorimotor experience.

Action Potentials↗

Spatial distribution of field potential profiles in the cat cerebellar cortex evoked by peripheral and central inputs.

The present study was designed to characterize the spread of excitation within the frontal plane of the cat cerebellar cortex following different types of stimuli. In particular, experiments were performed to determine whether the spread of excitation evoked by mossy fibre inputs proceeds primarily along the parallel fibres ("beam-like" spread) or whether these inputs activate non-propagated foci ("patches") in the cerebellar cortex. Field potentials were recorded within a frontal plane as a medial to lateral array at different depths in parallel tracks. The recordings were made following electrical stimulation of different forelimb nerves and functionally related areas of the sensorimotor cortex as well as during passive paw movements. The resulting spatial grid of responses provides discrete spatio-temporal information reflecting the activation of specific cerebellar afferents and the neuronal interactions they evoke. The method employed demonstrates the spatial distribution of the temporal sequence of excitability changes throughout all the cerebellar cortical layers. In general, the characteristics of the responses in the intermediate cerebellar cortex depended on the source of the signals. Activity patterns evoked by peripheral nerve stimulation showed more clustered foci compared with those following electrical stimulation of functionally related areas of the sensorimotor cortex. The centrally evoked profiles were generally more homogeneous. The largest number of foci were observed following passive movements around the wrist joint. The spread of excitation in the vertical direction was evaluated by the spatial shift of the line of reversal of the N3/P2-potential (zero-isopotential line). Lines of reversal for peripherally-evoked activity patterns were approximately 90 microns closer to the molecular layer than those evoked by central stimulation in animals in which recordings have been performed in lobule Vc. The opposite was found for recordings in lobule Vb, where potential reversals following peripheral stimulation were located 40 microns deeper than those evoked following central stimulation. Cortical inputs resulted in a more proximal activation of lobule Vc Purkinje cell dendrites than in lobule Vb. This type of input processing thus seems to be lobule dependent. A beam-like spread of excitation could not be demonstrated. For both climbing fibre and mossy fibre afferent systems multiple foci were found in the frontal plane. The foci due to mossy fibre activation arose from the granular layer and expanded vertically to the molecular layer. For the climbing fibre system the foci were restricted to the molecular layer, where they merged to form a superficial band of activation. Although the data presented in this paper favour a focal distribution of activity, they do not exclude beam-like propagation along the parallel fibres, because of the difficulty of detecting this pattern in response to the stimuli. The "beam"- and "patch"-like hypotheses need not be mutually exclusive. Each could contribute to a specific stage of the temporal-spatial processing in the cerebellar cortex in a functional and task-specific manner.

Animals↗

Impact of sensorimotor training on the rate of force development and neural activation.

The ability to generate high muscular strength within short time periods is of functional importance not only as a basic quality in many sports disciplines but also for active stabilization of joints. The rate of force development (RFD) is generally used to describe this ability. The purpose of the present study was to examine the functional adaptations of a specific sensorimotor training on the explosive strength qualities of the leg extensor muscles during maximum isometric actions. Force and surface EMG were recorded in 17 subjects before and after a 4-week sensorimotor training period. Maximum static leg press strength did not change [608.2 (47.0) N to 627.8 (48.4) N before/after training], whereas maximum RFD (RFD(max)) increased significantly from 4.95 (0.48) N/ms to 6.58 (0.76) N/ms (P<0.05). The gain in RFD(max) was accompanied by an increased EMG of the M. vastus medialis. Enhancement of neuromuscular activation was only prominent in the early phases of muscular action. Neither force nor EMG parameters revealed significant improvements for time phases beyond 100 ms following the onset of isometric action. Enhanced extrafacilitatory drive from the afferent system is discussed as a potential mechanism for the improved neural activation. From a more functional point of view, this type of adaptation may be helpful in various sport performances. Moreover, with regard to injury related situations, enhanced neuromuscular activation is of distinct relevance in order to stiffen joint complexes actively within short time periods.

Adaptation, Physiological↗

Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but enhances recovery of cognitive function following experimental traumatic brain injury in rats.

Traumatic brain injury causes long-term neurological motor and cognitive deficits, often with limited recovery. The inability of CNS axons to regenerate following traumatic brain injury may be due, in part, to inhibitory molecules associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal outgrowth and sprouting and improves outcome following experimental CNS insults. However, the involvement of Nogo-A in the neurobehavioral deficits observed in experimental traumatic brain injury remains unknown and was evaluated in the present study using the 11C7 monoclonal antibody against Nogo-A. Anesthetized, male Sprague-Dawley rats were subjected to either lateral fluid percussion brain injury of moderate severity (2.5-2.6 atm) or sham injury. Beginning 24 h post-injury, monoclonal antibody 11C7 (n=17 injured, n=6 shams included) or control Ab (IgG) (n=16 injured, n=5 shams included) was infused at a rate of 5 microl/h over 14 days into the ipsilateral ventricle using osmotic minipumps connected to an implanted cannula. Rats were assessed up to 4 weeks post-injury using tests for neurological motor function (composite neuroscore, and sensorimotor test of adhesive paper removal) and, at 4 weeks, cognition was assessed using the Morris water maze. Hippocampal CA3 pyramidal neuron damage and corticospinal tract sprouting, using an anterograde tracer (biotinylated dextran amine), were also evaluated. Brain injury significantly increased sprouting from the uninjured corticospinal tract but treatment with monoclonal antibody 11C7 did not further increase the extent of sprouting nor did it alter the extent of CA3 cell damage. Animals treated with 11C7 showed no improvement in neurologic motor deficits but did show significantly improved cognitive function at 4 weeks post-injury when compared with brain-injured, IgG-treated animals. To our knowledge, the present findings are the first to suggest that (1) traumatic brain injury induces axonal sprouting in the corticospinal tract and this sprouting may be independent of myelin-associated inhibitory factors and (2) that post-traumatic inhibition of Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal tract or neuroprotective effects on hippocampal cell loss following experimental traumatic brain injury.

Analysis of Variance↗

ERD/ERS patterns reflecting sensorimotor activation and deactivation.

Oscillations in the alpha and beta band (<35 Hz) show characteristic spatiotemporal patterns during sensorimotor processing. Whereas event-related desynchronization (ERD) during motor preparation, execution, and imagery can be seen as a correlate of an activated cortical area, event-related synchronization (ERS) of frequency components between 10 and 13 Hz may represent a deactivated cortical area or inhibited cortical network, at least under certain conditions. Induced beta rhythms (13-35 Hz, beta ERS) can be found in sensorimotor areas following both voluntary movement and somatosensory stimulation. In a recent study we used different tasks involving execution and imagery of movements of the upper and lower limb to produce activation vs. deactivation/inhibition of the sensorimotor hand area. Sensorimotor interference, as a function of the activation level of the motor cortex, was studied by the use of repetitive median nerve stimulation (MNS) (ISI 1.5 s) in 12 healthy volunteers during the following task conditions: (i) cube manipulation between thumb and fingers of one hand, (ii) imagined cube manipulation, (iii) continuous foot rotation movements, and (iv) imagined foot movements. EEG was recorded from hand and foot representation areas and processed time-locked to MNS (ERD/ERS). In addition, task-related band power changes (TRPD/TRPI) were analyzed. We found a clear-cut suppression of the stimulation-induced beta ERS (indicating an enhanced activity state of the sensorimotor areas) during active cube manipulation and a weaker suppression during cube imagery. Mental imagination of foot movement led to an increase of the hand area mu rhythm, but did not interfere with stimulation-related effects on beta ERS. These findings support that interfering sensorimotor activation and deactivation is reflected in graduated changes of induced mu and beta oscillations.

Beta Rhythm↗

Activation of the sensorimotor cortex at 1.0 T: comparison of echo-planar and gradient-echo imaging.

PURPOSE: The increasing demand for the clinical application of functional MR imaging raises the question of whether this technique can be routinely performed on 1.0-T MR scanners. To this end, we assessed the feasibility of functional MR imaging at 1.0 T. METHODS: Healthy volunteers were scanned during the performance of a motor task. Functional data were acquired with echo-planar imaging (EPI) and with gradient-echo (GRE) and dual-echo GRE sequences. The signal intensity variations of the EPI and GRE sequences were compared, and the influence of inflow and blood oxygen level-dependent (BOLD) effects on the signal variations was assessed with the dual-echo GRE sequences. RESULTS: In 11 of the 12 subjects we found activation in the primary motor cortex with both the GRE and EPI sequences. Active voxels had a significantly higher mean percentage of signal changes with the EPI sequence than with the GRE sequence (EPI: 1% to 6.1%, mean 2.4%; GRE: 1% to 4.5%, mean 1.9%). The EPI sequence was less sensitive to motion artifacts and enabled imaging of a larger brain volume in a shorter time. With a dual-echo sequence we found an increasing contribution of inflow effect with an increasing percentage of signal changes. CONCLUSION: Functional MR imaging of the sensorimotor cortex can be routinely performed at 1.0 T.

Adult↗

A 6 D.O.F. opto-inertial tracker for virtual reality experiments in microgravity.

Gravity plays a role in many different levels of human motor behavior. It dictates the laws of motion of our body and limbs, as well as of the objects in the external world with which we wish to interact. The dynamic interaction of our body with the world is molded within gravity's constraints. The role played by gravity in the perception of visual stimuli and the elaboration of human movement is an active research theme in the field of Neurophysiology. Conditions of microgravity, coupled with techniques from the world of virtual reality, provide a unique opportunity to address these questions concerning the function of the human sensorimotor system. The ability to measure movements of the head and to update in real time the visual scene presented to the subject based on these measurements is a key element in producing a realistic virtual environment. A variety of head-tracking hardware exists on the market today, but none seem particularly well suited to the constraints of working with a space station environment. Nor can any of the existing commercial systems meet the more stringent requirements for physiological experimentation (high accuracy, high resolution, low jitter, low lag) in a wireless configuration. To this end, we have developed and tested a hybrid opto-inertial 6 degree-of-freedom tracker based on existing inertial technology. To confirm that the inertial components and algorithms will function properly, this system was tested in the microgravity conditions of parabolic flight. Here we present the design goals of this tracker, the system configuration and the results of 0g and 1g testing.

Acceleration↗

Lesions of the rat piriform cortex prevent long-lasting sensorimotor gating deficits induced by stimulation of the ventral hippocampus.

Prepulse inhibition (PPI) is a cross-species operational measure of sensorimotor gating. Reduced PPI is found in schizophrenics and can be induced experimentally in rats. Stimulation of the rat ventral hippocampus (VH) with N-methyl-D-aspartate (NMDA) results in long-lasting PPI deficits (carry-over effect). Since we have previously shown that this carry-over effect was accompanied by increased expression of c-Fos in the piriform cortex (PIR), we here tested the effects of lesions of the PIR on PPI after stimulation of the VH. PIR lesioned rats still showed disruption of PPI after injection of NMDA into the VH. However, the carry-over effect observed in controls was prevented by PIR lesions. These data suggest that the PIR is important for long-lasting alterations in brain functioning leading to impaired sensorimotor gating.

Analysis of Variance↗

[Evidence-based arm rehabilitation--a systematic review of the literature].

Based on a systematic MEDLINE search and informal sources, 40 references were identified that evaluate training therapy or neuromuscular electric stimulation for arm paresis after stroke and describe either a systematic review, meta-analysis, randomised controlled trial, or controlled cohort study. The evidence was grouped into three areas of interest: comparison of physiotherapy schools, effects of intensity of training, and efficacy of specific arm rehabilitation techniques. The only physiotherapy school with evidence of superior efficacy was the task-oriented 'motor relearning programme'. Higher intensities of motor rehabilitation can accelerate motor recovery. Various training techniques with demonstrated efficacy are available for specific patient subgroups: arm ability training for mildly affected patients with reduced efficiency of motor control, constrained-induced movement therapy for patients with partial functional deficits and learned nonuse of the affected arm, and repetitive sensorimotor training techniques, EMG-biofeedback, functional electrical stimulation, and robot-assisted training for patients with severe arm paresis.

Arm↗

Neurorepair versus neuroprotection in stroke.

Stroke is the second to third leading cause of death and the main cause of severe, long-term disability in adults. However, treatment is almost reduced to fibrinolysis, a therapy useful in a low percentage of patients. Given that the immediate treatment for stroke is often unfeasible in the clinical setting, the need for new therapy strategies is imperative. After stroke, the remaining impairment in functions essential for routine activities, such as movement programming and execution, sensorimotor integration, language and other cognitive functions have a deep and life-long impact on the quality of life. An interesting point is that a slow but consistent recovery can be observed in the clinical practice over a period of weeks and months. Whereas the recovery in the first few days likely results from edema resolution and/or from reperfusion of the ischemic penumbra, a large part of the recovery afterwards is due mainly to brain plasticity, by which some regions of the brain assume the functions previously performed by the damaged areas. Neurogenesis and angiogenesis are other possible mechanisms of recovery after stroke. An understanding of the mechanisms underlying functional recovery may shed light on strategies for neurorepair, an alternative with a wide therapeutic window when compared with neuroprotective strategies.

Animals↗

Functional imaging of the brain in sedated newborn infants using near infrared topography during passive knee movement.

Near infrared topography was used for functional imaging of the sensorimotor cortex of newborn infants during passive knee movement under sedated sleep. Contralateral knee movement caused a marked increase in oxyhemoglobin and total hemoglobin from the baseline values at almost all locations in the primary sensorimotor area of all neonates and a decrease in local deoxyhemoglobin in six of seven neonates. During ipsilateral knee movement, oxyhemoglobin and total hemoglobin showed slighter changes at a few locations, equal to 30% (mean) and 29% (mean) of the changes that occurred with contralateral stimulation, respectively. The mean times corresponding to maximal changes were 11.9 s for oxyhemoglobin and 19.1 s for deoxyhemoglobin, demonstrating that oxyhemoglobin has a much faster response than does deoxyhemoglobin.

Brain Mapping↗

Effect of fMRI acoustic noise on sensorimotor activation examined using optical topography.

Functional magnetic resonance imaging (fMRI) is an important tool for noninvasively imaging the hemodynamic responses accompanying brain activity, but fMRI measurements are accompanied by loud acoustic noises resulting from Lorentz forces that cannot be completely excluded when the present technology is used. We used recorded fMRI acoustic noise and examined its effect on sensorimotor activation in optical topography measurement when subjects were instructed to tap the fingers of the right hand under a 23-dB non-noise condition and 46-, 56-, and 65-dB noise conditions. The results showed that the amplitude of the activation signal (relative change in concentration) for oxygenated hemoglobin in the sensorimotor cortex decreased with increasing noise. The activation signal for deoxygenated hemoglobin did not depend significantly on the noise level but did tend to decrease with increasing noise. These results suggest that fMRI acoustic noise affects the hemodynamics of cortical areas associated with the processing of information other than auditory information.

Adult↗

Adaptive reconfiguration of fractal small-world human brain functional networks.

Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a finger-tapping task, whereas the other half were studied at rest. We found that brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical delta (low and high), , alpha, beta, and gamma frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2-37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency gamma network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both beta and gamma networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding. Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters.

Brain↗

Accuracy and limitation of functional magnetic resonance imaging for identification of the central sulcus: comparison with magnetoencephalography in patients with brain tumors.

The aim of the present study was to clarify the accuracy and limitation of functional magnetic resonance imaging (fMRI) for the identification of the central sulcus affected by brain tumors. Twelve normal volunteers and 11 patients with intracranial tumors adjacent to the central sulcus underwent fMRI and magnetoencephalography (MEG). Three patients were evaluated again after surgery. fMRI was performed with a 1.5 Tesla scanner during repetitive opening and closing of each hand. Cross-correlation function was used to identify activation areas, and the central sulcus was defined as the nearest sulcus to the highest activation spots that were determined by elevating correlation coefficient threshold. Somatosensory-evoked fields were measured using a whole head MEG system. The central sulcus was defined as the nearest sulcus to the N20m for the median nerve stimulus. fMRI and MEG coincided in defining the central sulcus in all 24 hemispheres of volunteers and all 10 examined nonaffected hemispheres of patients. The fMRI-defined central sulcus coincided with the MEG-defined central sulcus in nine (82%) but did not in two (18%) affected hemispheres of patients. The preoperative mismatch disappeared after surgery in one of the two patients. The present study indicates that fMRI successfully defined the central sulcus in most of the patients with brain tumors. However, in a few cases, fMRI was not reliable probably due to venous flow changes by tumor compression and/or compensational activity by brain tissues surrounding the primary sensorimotor cortex. For precise functional assessment of the brain affected by intracranial tumors, combination of fMRI and MEG will be recommended.

Adult↗

MEG study of long-term cortical reorganization of sensorimotor areas with respect to using chopsticks.

The movements required to use chopsticks are overlearned and routine in Asians. Most non-Asians, on the other hand, typically have difficulty performing this unfamiliar manual activity, and have to focus their attention on the movements required to use chopsticks adequately. Using magnetoencephalography (MEG) we compared the cortical activation of highly trained Asian chopstick users to the activation of Europeans who only occasionally used chopsticks, while they performed the same tasks with chopsticks or a control task of simple tapping of the same fingers. The data were analyzed using the new method of synthetic aperture magnetometry (SAM). In Europeans there was a significantly higher ratio of spectral power in the higher gamma frequency band (60-80 Hz) over the sensorimotor area compared to the Asian subjects. From these results we conclude that the high gamma band activity in the sensorimotor area may reflect focused attention and functional reorganization of the cortical network with respect to sensorimotor experience.

Adult↗

Functional MR imaging activation after finger tapping has a shorter duration in the basal ganglia than in the sensorimotor cortex.

BACKGROUND AND PURPOSE: Repetitive motor tasks that produce sustained neuronal activity in the sensorimotor cortex produce transient neuronal activity in subcortical regions. We tested the hypothesis that a reference function modeling a transient hemodynamic response would more reliably detect activation in the basal ganglia than would a conventional reference function, which models a sustained hemodynamic response. METHODS: Functional MR imaging data were acquired in eight subjects performing an alternating-hand finger-tapping task. Postprocessing was performed by cross-correlation to two types of reference functions: one that models a sustained hemodynamic response to finger tapping and one that models an initial transient hemodynamic response. Activation in the sensorimotor cortex, supplementary motor area, cerebellum, thalamus, and corpus striatum was tabulated for each reference function. RESULTS: With the conventional boxcar reference function, activation was detected in the sensorimotor cortex, supplementary motor area, and cerebellum, but intermittently in the corpus striatum in all subjects. With the reference function for a transient response, activation in the corpus striatum was not detected in all subjects. CONCLUSION: In the corpus striatum, activation is detected more frequently with a reference function that models a transient response. Activated cortical and subcortical regions can be mapped with an alternating-hand finger-tapping paradigm and a combination of reference functions.

Adult↗