Effect of an attentional strategy on movement-related potentials recorded from subjects with Huntington's disease

Huntington's disease patients perform automatic movements in a bradykinetic manner, somewhat similar to patients with Parkinson's disease. Cortical activity relating to the preparation of movement in Parkinson's disease is significantly improved when a cognitive strategy is used. It is unknown whether patients with Huntington's disease can utilise an attentional strategy, and what effect this strategy would have on the premovement cortical activity. Movement-related potentials were recorded from 12 Huntington's disease patients and controls performing externally cued finger tapping movement, allowing an examination of cortical activity related to movement performance and bradykinesia in this disease. All subjects were tested in two conditions, which differed only by the presence or absence of the cognitive strategy. The Huntington's disease group, unlike controls, did not produce a rising premovement potential in the absence of the strategy. The Huntington's disease group did produce a rising premovement potential for the strategy condition, but the early slope of the potential was significantly reduced compared with the control group's early slope. These results are similar to those found previously with Parkinson's disease patients. The strategy may have put the task, which previously might have been under deficient automatic control, under attentional control. (C) 2002 Movement Disorder Society.

Movement-related potentials in Huntington's disease: movement preparation and execution

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD. particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

Magnetoencephalography reveals slowing of resting peak oscillatory frequency in children born very preterm

Resting cortical activity is characterized by a distinct spectral peak in the alpha frequency range. Slowing of this oscillatory peak toward the upper theta-band has been associated with a variety of neurological and neuropsychiatric conditions and has been attributed to altered thalamocortical dynamics. Children born very preterm exhibit altered development of thalamocortical systems. To test the hypothesis that peak oscillatory frequency is slowed in children born very preterm, we recorded resting magnetoencephalography (MEG) from school age children born very preterm (= 32 wk gestation) without major intellectual or neurological impairment and age-matched full-term controls. Very preterm children exhibit a slowing of peak frequency toward the theta-band over bilateral frontal cortex, together with reduced alpha-band power over bilateral frontal and temporal cortex, suggesting that mildly dysrhythmic thalamocortical interactions may contribute to altered spontaneous cortical activity in children born very preterm.

A novel reciprocal and biphasic relationship between membrane cholesterol and beta-secretase activity in SH-SY5Y cells and in human platelets.

Research into the cause of Alzheimer's disease (AD) has identified strong connections to cholesterol. Cholesterol and cholesterol esters can modulate amyloid precursor protein (APP) processing, thus altering production of the A beta peptides that deposit in cortical amyloid plaques. Processing depends on the encounter between APP and cellular secretases, and is thus subject to the influence of cholesterol-dependent factors including protein trafficking, and distribution between membrane subdomains. We have directly investigated endogenous membrane beta-secretase activity in the presence of a range of membrane cholesterol levels in SH-SY5Y human neuroblastoma cells and human platelets. Membrane cholesterol significantly influenced membrane beta-secretase activity in a biphasic manner, with positive correlations at higher membrane cholesterol levels, and negative correlations at lower membrane cholesterol levels. Platelets from individuals with AD or mild cognitive impairment (n = 172) were significantly more likely to lie within the negative correlation zone than control platelets (n = 171). Pharmacological inhibition of SH-SY5Y beta-secretase activity resulted in increased membrane cholesterol levels. Our findings are consistent with the existence of a homeostatic feedback loop between membrane cholesterol level and membrane beta-secretase activity, and suggest that this regulatory mechanism is disrupted in platelets from individuals with cognitive impairment.

Brain activity during ankle proprioceptive stimulation predicts balance performance in young and older adults

Proprioceptive information from the foot/ankle provides important information regarding body sway for balance control, especially in situations where visual information is degraded or absent. Given known increases in catastrophic injury due to falls with older age, understanding the neural basis of proprioceptive processing for balance control is particularly important for older adults. In the present study, we linked neural activity in response to stimulation of key foot proprioceptors (i.e., muscle spindles) with balance ability across the lifespan. Twenty young and 20 older human adults underwent proprioceptive mapping; foot tendon vibration was compared with vibration of a nearby bone in an fMRI environment to determine regions of the brain that were active in response to muscle spindle stimulation. Several body sway metrics were also calculated for the same participants on an eyes-closed balance task. Based on regression analyses, multiple clusters of voxels were identified showing a significant relationship between muscle spindle stimulation-induced neural activity and maximum center of pressure excursion in the anterior-posterior direction. In this case, increased activation was associated with greater balance performance in parietal, frontal, and insular cortical areas, as well as structures within the basal ganglia. These correlated regions were age- and foot-stimulation side-independent and largely localized to right-sided areas of the brain thought to be involved in monitoring stimulus-driven shifts of attention. These findings support the notion that, beyond fundamental peripheral reflex mechanisms, central processing of proprioceptive signals from the foot is critical for balance control.

Anticipatory Planning Reveals Segmentation of Cortical Motor Output During Action Observation

It has been argued that the variation in brain activity that occurs when observing another person reflects a representation of actions that is indivisible, and which plays out in full once the intent of the actor can be discerned. We used transcranial magnetic stimulation to probe the excitability of corticospinal projections to 2 intrinsic hand muscles while motions to reach and grasp an object were observed. A symbolic cue either faithfully indicated the required final orientation of the object and thus the nature of the grasp that was required, or was in conflict with the movement subsequently displayed. When the cue was veridical, modulation of excitability was in accordance with the functional role of the muscles in the action observed. If however the cue had indicated that the alternative grasp would be required, modulation of output to first dorsal interosseus was consistent with the action specified, rather than the action observed-until the terminal phase of the motion sequence during which the object was seen lifted. Modulation of corticospinal output during observation is thus segmented-it progresses initially in accordance with the action anticipated, and if discrepancies are revealed by visual input, coincides thereafter with that of the action seen.