Cortical beta oscillations are associated with motor performance following visuomotor learning.

People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15-30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18-30 years) and twenty elderly (62-77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested at two different time points (45-60 min and 24 h after initial training). Scalp EEG was recorded during a separate simple motor task before each training and retest session. Although short-term motor learning was comparable between young and elderly individuals, there was considerable variability within groups with subsequent analysis aiming to find the predictors of this variability. As expected, performance during the training phase was the best predictor of performance at later time points. However, regression analysis revealed that movement-related beta activity significantly explained additional variance in individual performance levels 45-60 min, but not 24 h after initial training. In the context of disease, these findings suggest that measurements of beta-band activity may offer novel targets for therapeutic interventions designed to promote rehabilitative outcomes.

Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich's ataxia.

Spinocerebellar ataxia type 3, spinocerebellar ataxia type 6 and Friedreich's ataxia are common hereditary ataxias. Different patterns of atrophy of the cerebellar cortex are well known. Data on cerebellar nuclei are sparse. Whereas cerebellar nuclei have long been thought to be preserved in spinocerebellar ataxia type 6, histology shows marked atrophy of the nuclei in Friedreich's ataxia and spinocerebellar ataxia type 3. In the present study susceptibility weighted imaging was used to assess atrophy of the cerebellar nuclei in patients with spinocerebellar ataxia type 6 (n = 12, age range 41-76 years, five female), Friedreich's ataxia (n = 12, age range 21-55 years, seven female), spinocerebellar ataxia type 3 (n = 10, age range 34-67 years, three female), and age- and gender-matched controls (total n = 23, age range 22-75 years, 10 female). T1-weighted magnetic resonance images were used to calculate the volume of the cerebellum. In addition, ultra-high field functional magnetic resonance imaging was performed with optimized normalization methods to assess function of the cerebellar cortex and nuclei during simple hand movements. As expected, the volume of the cerebellum was markedly reduced in spinocerebellar ataxia type 6, preserved in Friedreich's ataxia, and mildy reduced in spinocerebellar ataxia type 3. The volume of the cerebellar nuclei was reduced in the three patient groups compared to matched controls (P-values < 0.05; two-sample t-tests). Atrophy of the cerebellar nuclei was most pronounced in spinocerebellar ataxia type 6. On a functional level, hand-movement-related cerebellar activation was altered in all three disorders. Within the cerebellar cortex, functional magnetic resonance imaging signal was significantly reduced in spinocerebellar ataxia type 6 and Friedreich's ataxia compared to matched controls (P-values < 0.001, bootstrap-corrected cluster-size threshold; two-sample t-tests). The difference missed significance in spinocerebellar ataxia type 3. Within the cerebellar nuclei, reductions were significant when comparing spinocerebellar ataxia type 6 and Friedreich's ataxia to matched controls (P < 0.01, bootstrap-corrected cluster-size threshold; two-sample t-tests). Susceptibility weighted imaging allowed depiction of atrophy of the cerebellar nuclei in patients with Friedreich's ataxia and spinocerebellar ataxia type 3. In spinocerebellar ataxia type 6, pathology was not restricted to the cerebellar cortex but also involved the cerebellar nuclei. Functional magnetic resonance imaging data, on the other hand, revealed that pathology in Friedreich's ataxia and spinocerebellar ataxia type 3 is not restricted to the cerebellar nuclei. There was functional involvement of the cerebellar cortex despite no or little structural changes.

Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles.

Broca reported ~150 years ago that particular lesions of the left hemisphere impair speech. Since then, other brain regions have been reported to show lateralized structure and function. Yet, studies of brain asymmetry have limited their focus to pairwise comparisons between homologous regions. Here, we characterized separable whole-brain asymmetry patterns in grey and white matter structure from n = 37,441 UK Biobank participants. By pooling information on left-right shifts underlying whole-brain structure, we deconvolved signatures of brain asymmetry that are spatially distributed rather than locally constrained. Classically asymmetric regions turned out to belong to more than one asymmetry pattern. Instead of a single dominant signature, we discovered complementary asymmetry patterns that contributed similarly to whole-brain asymmetry at the population level. These asymmetry patterns were associated with unique collections of phenotypes, ranging from early lifestyle factors to demographic status to mental health indicators.

Sensorimotor cortex beta oscillations reflect motor skill learning ability after stroke.

Recovery of skilled movement after stroke is assumed to depend on motor learning. However, the capacity for motor learning and factors that influence motor learning after stroke have received little attention. In this study, we first compared motor skill acquisition and retention between well-recovered stroke patients and age- and performance-matched healthy controls. We then tested whether beta oscillations (15-30 Hz) from sensorimotor cortices contribute to predicting training-related motor performance. Eighteen well-recovered chronic stroke survivors (mean age 64 ± 8 years, range: 50-74 years) and 20 age- and sex-matched healthy controls were trained on a continuous tracking task and subsequently retested after initial training (45-60 min and 24 h later). Scalp electroencephalography was recorded during the performance of a simple motor task before each training and retest session. Stroke patients demonstrated capacity for motor skill learning, but it was diminished compared to age- and performance-matched healthy controls. Furthermore, although the properties of beta oscillations prior to training were comparable between stroke patients and healthy controls, stroke patients did show less change in beta measures with motor learning. Lastly, although beta oscillations did not help to predict motor performance immediately after training, contralateral (ipsilesional) sensorimotor cortex post-movement beta rebound measured after training helped predict future motor performance, 24 h after training. This finding suggests that neurophysiological measures such as beta oscillations can help predict response to motor training in chronic stroke patients and may offer novel targets for therapeutic interventions.

Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers.

The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain's prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration.

Transcranial direct current stimulation of right dorsolateral prefrontal cortex does not affect model-based or model-free reinforcement learning in humans.

There is broad consensus that the prefrontal cortex supports goal-directed, model-based decision-making. Consistent with this, we have recently shown that model-based control can be impaired through transcranial magnetic stimulation of right dorsolateral prefrontal cortex in humans. We hypothesized that an enhancement of model-based control might be achieved by anodal transcranial direct current stimulation of the same region. We tested 22 healthy adult human participants in a within-subject, double-blind design in which participants were given Active or Sham stimulation over two sessions. We show Active stimulation had no effect on model-based control or on model-free ('habitual') control compared to Sham stimulation. These null effects are substantiated by a power analysis, which suggests that our study had at least 60% power to detect a true effect, and by a Bayesian model comparison, which favors a model of the data that assumes stimulation had no effect over models that assume stimulation had an effect on behavioral control. Although we cannot entirely exclude more trivial explanations for our null effect, for example related to (faults in) our experimental setup, these data suggest that anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex does not improve model-based control, despite existing evidence that transcranial magnetic stimulation can disrupt such control in the same brain region.

Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging.

A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19-75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.

Effects of focal basal ganglia lesions on timing and force control.

Studies of basal ganglia dysfunction in humans have generally involved patients with degenerative disorders, notably Parkinson's disease. In many instances, the performance of these patients is compared to that of patients with focal lesions of other brain structures such as the cerebellum. In the present report, we studied the performance of patients with focal basal ganglia lesions on three fundamental motor tasks. The patients all had suffered unilateral damage in the striatum and were tested in the chronic state. The first task required the participants to tap with their index finger as fast as possible; this test provided a simple assessment of motor competence. Compared to controls, the maximum tapping rate was lower for the patients when tapping with their contralesional limb, although the deficit was not severe. The second and third tasks were designed to assess timing and force control, two functions that have been associated with basal ganglia function. The patients performed similar to controls on both tasks and showed no evidence of impairment when using their contralesional limb compared to their ipsilesional limb. The results indicate that unilateral basal ganglia lesions tend to produce minor motor problems in force control, and fail to support the hypothesized role of the basal ganglia in timing.

Bimanual cross-talk during reaching movements is primarily related to response selection, not the specification of motor parameters.

Simultaneous reaching movements made with the two hands can show a considerable increase in reaction time (RT) when they differ in terms of direction or extent, compared to when the movements involve the same direction and extent. This cost has been attributed to cross-talk in the specification of the motor parameters for the two hands. However, a recent study [Diedrichsen, Hazeltine, Kennerley, & Ivry, (2001). Psychological Science, 12, 493-498] indicates that when reaching movements are cued by the onset of the target endpoint, no compatibility effects are observed. To determine why directly cued movements are immune from interference, we varied the stimulus onset asynchrony for the two movements and used different combinations of directly cued and symbolically cued movements. In two experiments, compatibility effects were only observed when both movements were symbolically cued. No difference was found between compatible and incompatible movements when both movements were directly cued or when one was directly cued and the other was symbolically cued. These results indicate that interference is not related to the specification of movement parameters but instead emerges from processes associated with response selection. Moreover, the data suggest that cross-talk, when present, primarily shortens the RT of the second movement on compatible trials rather than lengthening this RT on incompatible trials.