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 Parkinson's 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.

Cognitive aspects of freezing of gait in Parkinson's disease: a challenge for rehabilitation.

Freezing of gait (FOG) is a very disabling symptom affecting up to half of the patients with Parkinson's disease (PD). Evidence is accumulating that FOG is caused by a complex interplay between motor, cognitive and affective factors, rather than being a pure motor phenomenon. In the current paper, we review the evidence on the specific role of cognitive factors in FOG. Results from behavioral studies show that patients with FOG experience impairments in executive functioning and response selection which predict that motor learning may be compromised. Brain imaging studies strengthen the neural basis of a potential association between FOG and cognitive impairment, but do not clarify whether it is a primary or secondary determinant of FOG. A FOG-related reduction of cognitive resources implies that adaptation of rehabilitation interventions is indicated for patients with FOG to promote the consolidation of learning.

Center of mass trajectories during turning in patients with Parkinson's disease with and without freezing of gait.

BACKGROUND: Despite the strong relationship between freezing of gait (FOG) and turning in Parkinson's disease (PD), few studies have addressed specific postural characteristics during turning that might contribute to freezing. METHODS: Thirty participants with PD (16 freezers, 14 non-freezers) (all tested OFF medication) and 14 healthy controls walked 5 meters and turned 180° in a 3D gait laboratory. COM behavior was analyzed during four turning quadrants of 40° between 10° and 170° pelvic rotation and during 40° before actual FOG episodes. These pre-FOG segments were compared with similar turning sections in turns of freezers without FOG. Outcome parameters were turn time, COM distance, COM velocity, step width and the medial- and anterior COM position. RESULTS: Turn time was increased in freezers compared to non-freezers (p=.000). No differences were found regarding COM distance and velocity during turning quadrants between groups and between freezers' pre-FOG segments and similar turning segments without FOG. Medial COM deviation was reduced in PD patients compared to controls (p=.004), but no differences were found between freezers and non-freezers. In turns with freezing, turn time increased (p=.005) and step width decreased (p=.025) pre-FOG. Freezers also showed a less medial (p=.020) and more anterior (p=.016) COM position pre-FOG compared to turning sections without FOG. CONCLUSIONS: Our results revealed no subgroup differences in COM behavior during uninterrupted turning. However, we found a reduced medial deviation, a forward COM shift and a decreased step width in freezers just before FOG episodes. These abnormalities may play a causal role, as they could hamper stability and fluent weight shifting necessary for continued stepping during turning.

Cued motor imagery in patients with multiple sclerosis.

Motor imagery (MI) is a promising practice tool in neurorehabilitation. However, in patients with multiple sclerosis (MS), impairments in MI accuracy and temporal organization were found during clinical assessment, which may limit the benefits of MI practice. Therefore, we investigated whether the MI quality of MS patients could be optimized by means of external cueing. Fourteen patients with MS and 14 healthy control patients physically executed and visually imagined a goal-directed upper limb task in the presence and absence of added visual and auditory cues. MI quality was assessed by means of eye-movement registration. As main results, it was found that MS patients had significant higher eye-movement times than controls during both execution and imagery, and overestimated the to-be-imagined movement amplitude when no external information was provided during imagery. External cues, however, decreased patients' MI duration and increased the spatial accuracy of their imagined movements. In sum, our results indicate that MS patients imagine movements in a better way when they are provided with external cues during MI. These findings are important for developing rehabilitation strategies based on MI in patients with MS.

Turning and unilateral cueing in Parkinson's disease patients with and without freezing of gait.

BACKGROUND: Freezing of gait (FOG) is one of the most disabling symptoms in Parkinson's disease (PD), and cueing has been reported to improve FOG during straight-line walking. Studies on how cueing affects FOG during turning are lacking. Given the asymmetrical nature of turning and the asymmetrical disease expression, we aimed to gain a new perspective on how unilateral cueing may alleviate FOG. OBJECTIVE: To explore disease dominance and turning side as contributing factors to turning problems and FOG and to investigate the effect of unilateral cueing. METHODS: In the first study, 13 PD patients with FOG (freezers) and 13 without FOG (nonfreezers) turned toward their disease-dominant and nondominant side (off medication). During the second study, 16 freezers and 14 nonfreezers turned with and without a unilateral auditory cue at -10% of preferred cadence. Total number of steps, turn duration, cadence, and FOG episodes were measured using VICON. RESULTS: Cadence, but not FOG frequency, was higher when turning toward the disease-dominant side. FOG started more frequently (64.9%) on the inner side of the turning cycle. Unilateral cueing seemed to prevent FOG in most patients, irrespective of the side at which the cue was offered. A carryover effect was found for cadence during turning, but the effect on FOG disappeared when the cue was removed. CONCLUSIONS: The occurrence of FOG is not influenced by turning toward the disease-dominant or nondominant side, which is confirmed by the fact that it does not make a difference at which side unilateral cueing is applied. Cueing reduces FOG during turning, but these effects disappear dramatically after cue removal. This raises further questions as to the influence of training on cue dependency and on the feasibility of either continuous application of cues or using cognitive strategies as an alternative.

Conflict and freezing of gait in Parkinson's disease: support for a response control deficit.

We investigated response activation and suppression processes in Parkinson's disease patients with freezing of gait (FOG). Fourteen freezers, 14 nonfreezers, and 14 matched healthy controls performed the attention network task (ANT) and the Stroop task. The former task has more stimulus-response overlap and is expected to elicit stronger irrelevant response activation, requiring more inhibition. Congruency effects were used as a general measure of conflict resolution. Supplementary reaction time (RT) distribution analyses were utilized to calculate conditional accuracy functions (CAFs) and delta plots to measure response activation and suppression processes. In agreement with previous research, freezers showed a general conflict resolution deficit compared with nonfreezers and healthy controls. Moreover, CAFs pointed to a strong initial incorrect response activation in FOG. As expected, conflict resolution impairment was only apparent in the ANT, and not in the Stroop task. These results suggest an imbalance between automatic and controlled processes in FOG, leading to a breakdown in both motor and cognitive response control.

Freezing of gait in Parkinson's disease: disturbances in automaticity and control.

Recent studies emphasize a key role of controlled operations, such as set-shifting and inhibition, in the occurrence of freezing of gait (FOG) in Parkinson's disease (PD). However, FOG can also be characterized as a de-automatization disorder, showing impairments in both the execution and acquisition of automaticity. The observed deficits in automaticity and executive functioning indicate that both processes are malfunctioning in freezers. Therefore, to explain FOG from a cognitive-based perspective, we present a model describing the pathways involved in automatic and controlled processes prior to a FOG episode. Crucially, we focus on disturbances in automaticity and control, regulated by the frontostriatal circuitry. In complex situations, non-freezing PD patients may compensate for deficits in automaticity by switching to increased cognitive control. However, as both automatic and controlled processes are more severely impaired in freezers, this hampers cognitive compensation in FOG, resulting in a potential breakdown. Future directions for cognitive rehabilitation are proposed, based on the cognitive model we put forward.