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.

Bimanual co-ordination in Huntington's disease

The ability of Huntington's disease patients to co-ordinate their two hands with and without external cueing was investigated. Twelve Huntington's disease patients and sex- and age-matched controls performed a bimanual cranking task at two speeds (0.5 Hz, 1.5 Hz) and phase relationships (in-phase, anti-phase), with and without an external metronome cue. Data were sampled at 200 Hz, and raw displacement data for each hand, mean and standard deviation measures of the relative positions of the two hands and their velocities were then calculated. All participants could perform the in-phase movement, at both speeds; however, the Huntington's disease patients were more variable and less accurate than the control participants, particularly at the fast speed. While controls could perform the anti-phase movement, in which rotation of the cranks differed by 180 degrees at both speeds, Huntington's disease patients were unable to do so at either speed, reverting to the in-phase movement at the slow speed. An external metronome cue did not improve the performance of the Huntington's disease patients, which differentiated this group from patients suffering from Parkinson's disease. The Huntington's disease patients' inability to perform the anti-phase movement may be due to damage to the basal ganglia and its output regions.

Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 (D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.