Jan E. Timmermann

Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive Stimulation

Cerebellar transcranial direct current stimulation (tDCS) has the potential to modulate cerebellar outputs and visuomotor adaptation. The cerebellum plays a pivotal role in the acquisition and control of skilled hand movements, especially its temporal aspects. We applied cerebellar anodal tDCS concurrently with training of a synchronization-continuation motor task. We hypothesized that anodal cerebellar tDCS will enhance motor skill acquisition. Cerebellar tDCS was applied to the right cerebellum in 31 healthy subjects in a double-blind, sham-controlled, parallel design. During synchronization, the subjects tapped the sequence in line with auditory cues. Subsequently, in continuation, the learned sequence was reproduced without auditory cuing. Motor task performance was evaluated before, during, 90 min, and 24 h after training. Anodal cerebellar tDCS, compared with sham, improved the task performance in the follow-up tests (F1,28 = 5.107, P = 0.032) of the synchronization part. This effect on retention of the skill was most likely mediated by enhanced motor consolidation. We provided first evidence that cerebellar tDCS can enhance the retention of a fine motor skill. This finding supports the promising approach of using noninvasive brain stimulation techniques to restore impaired motor functions in neurological patients, such after a stroke.

White Matter Integrity of Specific Dentato-Thalamo-Cortical Pathways is Associated with Learning Gains in Precise Movement Timing

The dentato-thalamo-cortical tract (DTCT) connects the lateral cerebellum with contralateral motor and nonmotor areas, such as the primary motor cortex (M1), the ventral premotor cortex (PMv), and the dorsolateral prefrontal cortex (DLPFC). As the acquisition of precisely timed finger movements requires the interplay between these brain regions, the structural integrity of the underlying connections might explain variance in behavior. Diffusion tensor imaging was used to 1) reconstruct the DTCT connecting the dentate nucleus with M1, PMv, and DLPFC and 2) examine to which extent their microstructural integrity (tract-related fractional anisotropy) relates to learning gains in a motor-sequence learning paradigm consisting of a synchronization and continuation part. Continuous DTCT were reconstructed from the dentate nucleus to all cortical target areas. We found that the microstructural integrity of the DTCT connecting the left dentate nucleus with the right DLPFC was associated with better early consolidation in rhythm continuation (R = -0.69, P = 0.02). The present data further advances the knowledge about a right-hemispheric timing network in the human brain with the DLPFC as an important node contributing to learning gains in precise movement timing.

Cortico-Cerebellar Structural Connectivity Is Related to Residual Motor Output in Chronic Stroke

Abstract Functional imaging studies have argued that interactions between cortical motor areas and the cerebellum are relevant for motor output and recovery processes after stroke. However, the impact of the underlying structural connections is poorly understood. To investigate this, diffusion‐weighted brain imaging was conducted in 26 well‐characterized chronic stroke patients (aged 63 ± 1.9 years, 18 males) with supratentorial ischemic lesions and 26 healthy participants. Probabilistic tractography was used to reconstruct reciprocal cortico‐cerebellar tracts and to relate their microstructural integrity to residual motor functioning applying linear regression modeling. The main finding was a significant association between cortico‐cerebellar structural connectivity and residual motor function, independent from the level of damage to the cortico‐spinal tract. Specifically, white matter integrity of the cerebellar outflow tract, the dentato‐thalamo‐cortical tract, was positively related to both general motor output and fine motor skills. Additionally, the integrity of the descending cortico‐ponto‐cerebellar tract contributed to rather fine motor skills. A comparable structure‐function relationship was not evident in the controls. The present study provides first tract‐related structural data demonstrating a critical importance of distinct cortico‐cerebellar connections for motor output after stroke.

White matter integrity of motor connections related to training gains in healthy aging

Impaired motor skill acquisition is a feature of older age. Acquisition of new motor skills requires the interplay between different cortical motor areas. Using diffusion tensor imaging we reconstructed cortico-cortical connections between the primary motor cortex (M1) and secondary motor areas in 11 older and 11 young participants who took part in a motor skill acquisition paradigm with the nondominant left hand. Examining the extent to which tract-related integrity correlated with training gains we found that white matter integrity of fibers connecting contralateral M1 with both contralateral (r = 0.85) and ipsilateral supplementary motor areas (r = 0.92) were positively associated in old participants. Also, fibers connecting contralateral M1 with ipsilateral dorsal premotor (r = 0.82) and fibers connecting ipsilateral dorsal premotor and supplementary motor area (r = 0.88) were positively related to skill acquisition (all p < 0.05). A similar structure-behavior relationship was not present in the young control subjects suggesting a critical role of brain structural integrity for motor learning in healthy aging.

Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

Background Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? Methods We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. Findings NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. Interpretations Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

Spectral Variability in the Aged Brain during Fine Motor Control.

Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role.

Eyelid myokymia in an older subject after repetitive sessions of anodal transcranial direct current stimulation.

Note: Letter Reference EPFL-ARTICLE-223949doi:10.1016/j.brs.2012.09.002 Record created on 2016-12-27, modified on 2016-12-27

Causal role of the inferolateral prefrontal cortex in balancing goal-directed and habitual control of behavior

Successful adaptation to complex environments depends on the balance of at least two systems: a flexible but slow goal-directed system encoding action-outcome associations and an efficient but rigid habitual system linking responses to preceding stimuli. Recent evidence suggests that the inferolateral prefrontal cortex (ilPFC), a region well known to contribute to cognitive control processes, may play a crucial role in the balance of goal-directed and habitual responding. This evidence, however, comes mainly from correlational data and whether the ilPFC is indeed causally involved in the goal-directed vs. habitual control of behavior is unclear. Here, we used neuro-navigated theta-burst stimulation (TBS) to either inhibit or enhance right ilPFC functionality before participants completed an instrumental learning task designed to probe goal-directed vs. habitual behavioral control. TBS did not affect overall learning performance. However, participants that had received inhibitory TBS were less able to adapt their behavior to altered task demands, indicating a shift from goal-directed towards more habitual control of behavior. Sham or excitatory TMS groups showed no such effect and were comparable in their performance to an unstimulated control group. Our findings indicate a causal role of the ilPFC in the balance of goal-directed vs. habitual control of behavior.