Nici Wenderoth

The Neural Correlates of Upper Limb Motor Blocks in Parkinson's Disease and Their Relation to Freezing of Gait

Due to basal ganglia dysfunction, bimanual motor performance in Parkinson patients reportedly relies on compensatory brain activation in premotor-parietal-cerebellar circuitries. A subgroup of Parkinsons disease (PD) patients with freezing of gait (FOG) may exhibit greater bimanual impairments up to the point that motor blocks occur. This study investigated the neural mechanisms of upper limb motor blocks and explored their relation with FOG. Brain activation was measured using functional magnetic resonance imaging during bilateral finger movements in 16 PD with FOG, 16 without FOG (PD + FOG and PD - FOG), and 16 controls. During successful movement, PD + FOG showed decreased activation in right dorsolateral prefrontal cortex (PFC), left dorsal premotor cortex (PMd), as well as left M1 and bilaterally increased activation in dorsal putamen, pallidum, as well as subthalamic nucleus compared with PD - FOG and controls. On the contrary, upper limb motor blocks were associated with increased activation in right M1, PMd, supplementary motor area, and left PFC compared with successful movement, whereas bilateral pallidum and putamen activity was decreased. Complex striatofrontal activation changes may be involved in the difficulties of PD + FOG to perform bimanual movements, or sequential movements in general. These novel results suggest that, whatever the exact underlying cause, PD + FOG seem to have reached a saturation point of normal neural compensation and respond belatedly to actual movement breakdown.

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children, during active and passive movements, and tactile stimulation? An fMRI study.

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.

Ipsilateral coordination at preferred rate: effects of age, body side and task complexity.

Functional imaging studies have shown that elderly individuals activate widespread additional brain networks, compared to young subjects, when performing motor tasks. However, the parameters that effect this unique neural activation, including the spatial distribution of this activation across hemispheres, are still largely unknown. Here, we examined the effect of task complexity and body side on activation differences between older and younger adults while performing cyclical flexion-extension movements of the ipsilateral hand and foot. In particular, easy (isodirectional) and more difficult (non-isodirectional) coordination patterns were performed with either the left or right body side at a self-selected, comfortable rate. Even in the absence of imposed pacing the older group activated a larger brain network, suggestive of increased attentional deployment for monitoring the spatial relationships between the simultaneously moving segments and enhanced sensory processing and integration. Evidence of age-dependent underactivation was also found in contralateral M1, SMA and bilateral putamen, possibly reflecting a functional decline of the basal ganglia-mesial cortex pathway in the older group. An ANOVA model revealed significant main effects of task complexity and body side. However the interaction of these factors with age did not reach significance. Consequently, we conclude that under self-paced conditions, task complexity and body side did not have a modulatory effect on age-related brain activation.

Hemispheric asymmetries in eye-hand coordination

Manual asymmetries in limb kinematics and eye-hand coordination have usually been attributed to differences in online processing capabilities between the left and the right cerebral hemisphere. In the present fMRI experiment, we examined in right handers the brain areas involved in eye-hand coordination with either the left or the right hand. Although temporal and spatial accuracy was equal for left- and right-hand movements, manual asymmetries were found in behavioral and neurophysiologic data, suggesting an asymmetric mode of control for left vs. right eye-hand coordination. For left eye-hand coordination, peak velocity and saccade completion occurred earlier than for the contralateral movements, suggesting that there was more time needed for homing-in on the target. When using the right hand, there was more activation in occipital areas. This might indicate a more intense visual processing or visualization of the target locations. When using the left hand, there was more activation in sensorimotor areas, frontal areas and cerebellum. This might point toward more processing effort. Left-hand movements may be considered as more difficult than right-hand movements by right-handed participants. Alternatively and more likely, these findings might reflect a difference in attention or resources attributed to different aspects of the tasks because of the different functional specializations of both hand/hemisphere systems.

Hemispheric asymmetries in goal-directed hand movements are independent of hand preference

Asymmetries in the kinematics and neural substrates of voluntary right and left eye-hand coordinated movements have been accredited to differential hemispheric specialization. An alternative explanation for between-hand movement differences could result from hand preference related effects. To test both assumptions, an experiment was conducted with left- and right-handers performing goal-directed movements with either hand paced by a metronome. Spatiotemporal accuracy was comparable between hands, whereas hand peak velocity was reached earlier when moving with the left compared to the right hand. The underlying brain activation patterns showed that both left- and right-handers activated more areas involved in visuomotor attention and saccadic control when using their left compared to the right hand. Altogether, these results confirm a unique perceptuomotor processing specialization of the left brain/right hand system that is independent of hand preference.

Does somatosensory discrimination activate different brain areas in children with unilateral cerebral palsy compared to typically developing children? An fMRI study

Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during somatosensory discrimination exercises, are lacking in CP children. Therefore, this study investigated brain activation with functional magnetic resonance imaging (fMRI) during passively guided somatosensory discrimination exercises in 18 typically developing children (TD) (age, M=14 ± 1.92 years; 11 girls) and 16 CP children (age, M=15 ± 2.54 years; 8 girls). The demographic variables between both groups were not statistically different. An fMRI compatible robot guided the right index finger and performed pairs of unfamiliar geometric shapes in the air, which were judged on their equality. The control condition comprised discrimination of music fragments. Both groups exhibited significant activation (FDR, p<.05) in frontoparietal, temporal, cerebellar areas, and insula, similar to studies in adults. The frontal areas encompassed ventral premotor areas, left postcentral gyrus, and precentral gyrus; additional supplementary motor area (SMA proper) activation in TD; as well as dorsal premotor, and parietal operculum recruitment in CP. On uncorrected level, p<.001, TD children revealed more left frontal lobe, and right cerebellum activation, compared to CP children. Conversely, CP children activated the left dorsal cingulate gyrus to a greater extent than TD children. These data provide incentives to investigate the effect of somatosensory discrimination during rehabilitation in CP, on clinical outcome and brain plasticity.

PTMS62 Hemispheric asymmetries of the ventral and dorsal premotor cortex in coordination movements as revealed by disruptive transcranial magnetic stimulation

Introduction: Estimation of response thresholds is widely used in various transcranial magnetic stimulation (TMS) paradigms and is critical to the reliability of experimental results as well as the safety and efficacy of therapeutic applications. Existent methods are time consuming and lack rigorous characterization of their accuracy. Objectives: Existing TMS threshold estimation approaches, algorithms used in other fields, and novel algorithms were compared to evaluate the tradeoff between the number of steps and estimation error. Methods: We simulated the widely used 5/10 procedure, parametric approaches (Awiszus’ maximum likelihood, Bayesian, and a-posteriori estimation), and several non-parametric Robbins-Monro-based rootfinding algorithms. The response recruiting curve and variability were modeled based on corticospinal motor evoked potential (MEP) data. Results: The 5/10 procedure had median duration of 35 steps and median estimate error of 2%. All other algorithms reached 2% median error level within 13 steps. The best performance was observed for a non-parametric algorithm utilizing analog MEP amplitude information; it reached 2% median error within 10 steps and reduced error most rapidly with subsequent steps. The Bayesian and a-posteriori estimators had a slower rate of error reduction. Awiszus’ method performed worst, its error plateauing near 2% after the 17th step. Conclusions: A wide range of parametric and non-parametric algorithms perform better than the conventional 5/10 threshold estimation procedure. Compared to the 5/10 approach, such alternative algorithms could reduce the duration of the procedure by as much as 3-fold for the same accuracy, or reduce the estimate error in half within the same procedure duration. Relatively simple non-parametric algorithms may offer the best performance; their robustness and optimal rule selection should be explored further. Awiszus’ method is inefficient for accurate threshold estimation.