Copper-catalyzed Hiyama cross-coupling using vinylsilanes and benzylic electrophiles.

Allylbenzene derivatives are ubiquitous frameworks in organic chemistry. Herein is described an efficient copper-catalyzed cross-coupling reaction using vinylsilanes and benzyl bromides, leading to the synthesis of allylbenzenes. This methodology allows the use of cis, trans and 1,1'-disubstituted vinylsilanes as well as a large number of sensitive moieties.

Freezing beyond gait in Parkinson's disease: a review of current neurobehavioral evidence.

Besides the continuous motor impairments that characterize Parkinson's disease (PD), patients are frequently troubled by sudden paroxysmal arrests or brief episodes of movement breakdown, referred to as 'freezing'. Freezing of gait (FOG) is common in advanced PD and typically occurs in walking conditions that challenge dynamic motor-cognitive control. Mounting evidence suggests that episodic motor phenomena during repetitive upper limb (e.g. writing), lower limb (e.g. foot tapping) and speech sequences resemble FOG and may share some underlying neural mechanisms. However, the precise association between gait and non-gait freezing phenomena remains controversial. This review aimed to clarify this association based on literature on non-gait freezing published between 2000 and 2013. We focused on clinical and epidemiological features of the episodes and their relevance to current influential models of FOG, including recent neuroimaging studies that used a non-gait freezing paradigm as a proxy for FOG. Although not capturing the full complexity of FOG, the neurobehavioral insights obtained with non-gait freezing paradigms will contribute to an increased understanding of disturbed brain-behavior output in PD.

Effects of deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease: a prospective controlled study.

BACKGROUND: Freezing of gait (FOG) is a debilitating gait disorder in Parkinson's disease (PD) with partial responsiveness to dopaminergic medication. To date, notions about the effects of subthalamic deep brain stimulation (STN-DBS) on FOG remain controversial. OBJECTIVES: To compare the effects of bilateral STN-DBS and continued best medical treatment (BMT) on FOG occurrence, FOG severity and clinical outcomes in PD patients at 6 and 12 months follow-up. METHODS: In this prospective, controlled study, 41 PD patients with at least 5 years disease duration participated. Twenty-four subjects (20 with FOG) were treated with STN-DBS and seventeen (15 with FOG) continued BMT. The primary outcome was the New Freezing of Gait Questionnaire (NFOGQ) at 6 months postsurgery. Other outcomes were the NFOGQ at 12 months and clinical outcomes (Unified Parkinson's Disease Rating Scale III (UPDRS III), timed gait, falls and quality of life) at both time points. RESULTS: STN-DBS increased the likelihood to convert from being a freezer to a non-freezer at 6 and 12 months follow-up (relative risk reduction=0.4). However, 45% of baseline freezers still experienced FOG 6 and 12 months postsurgery although with reduced severity. Three baseline non-freezers (1/2 BMT-treated, 2/4 STN-DBS-treated) developed FOG during follow-up. STN-DBS-induced benefits on FOG were mostly mediated by baseline levodopa equivalent dose, altered medication-intake and reduced motor fluctuations. CONCLUSIONS: In contrast to continued BMT, STN-DBS reduced FOG occurrence and severity at 6 months postsurgery with largely sustained effects at 12 months follow-up. Longer follow-up periods are needed to test whether FOG improvements after STN-DBS persist with disease progression.

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.

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.

Keeping an eye on imagery: the role of eye movements during motor imagery training.

We recently found that spontaneous eye movements occur during motor imagery of hand movements, which are similar to those made during physical execution. In physical execution, eye movements have been shown to play an important role during training. In motor imagery practice, however, their effect remains unclear. Therefore, in the present study, we examined the role of eye movements during motor imagery practice with specific interest in the impact of task complexity and effector specificity. Thirty-six young healthy participants were tested before and after 4 days of visual motor imagery training on a Virtual Radial Fitts' task with different indices of difficulty. Training was performed with the nondominant hand only. Subjects were divided into a group that trained while spontaneous eye movements were allowed, one that kept the eyes fixed during training, and a control group. Electro-oculography and electromyography signals were monitored to guarantee task compliance during imagery. The results indicated that eye movements during imagery did not affect the temporal parameters of the trained movement. They did, however, help to achieve maximal gains in movement accuracy and efficiency. These positive effects on the spatial parameters were most pronounced during conditions with high accuracy demands and were present for both the trained and the untrained hand. These findings contribute to guidelines for optimizing training protocols based on motor imagery.