Jochen Vandenbossche

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

We investigated response activation and suppression processes in Parkinsons 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 Disease Is Associated With Impaired Conflict Resolution

Background. Freezing of gait (FOG) in Parkinson disease (PD) may involve executive dysfunction. This study examined whether executive functioning and attention are more affected in patients with FOG compared with those without and determined whether these processes are influenced by anti-Parkinson medication. Methods. A total of 11 PD patients with FOG, 11 without FOG, and 10 healthy control subjects, matched for age, gender, and education, participated. General motor, mental and cognitive screening tests, as well as specific neuropsychological assessment of executive functions and the Attention Network Test (ANT) were administered. The ANT was conducted in both ON and OFF phases in a counterbalanced design to determine medication-specific effects. Results. FOG showed a clear association with impairment in the executive control network for conflict resolution (inhibition of unwanted responses and impaired response selection), compared with nonfreezers and healthy controls, F(2, 28) = 5.41, P = .01. Orienting and alerting function did not differ between groups, F < 1. Other executive functions, such as abstract problem solving and mental flexibility were not associated with FOG (P > .10). Anti-Parkinson medication did not ameliorate conflict resolution (P > .10), although orienting attention improved with medication, F(1, 17) = 9.81, P < .01. Conclusions. This study shows an association between impaired conflict resolution and FOG, important in understanding the interplay between cognitive and motor problems, which can lead to specific rehabilitation strategies.

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 Parkinsons 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.

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.

Abnormalities and Cue Dependence of Rhythmical Upper-Limb Movements in Parkinson Patients With Freezing of Gait

Background. Freezing of gait (FOG) is a significant clinical problem in Parkinson disease (PD). Similar freezing-like episodes occur during finger movements, but little is known about ongoing motor problems during repetitive hand movements. Objective. To investigate if the regulation of bimanual movements is impaired in those with FOG and if withdrawal of an auditory cue amplifies this problem. Methods. A total of 23 PD patients (11 with and 12 without FOG) and 11 controls (CTRLs) performed repetitive finger movements, either externally paced or following cue withdrawal. Movement frequency, amplitude, and coordination pattern were manipulated. The stability and accuracy of movement were evaluated after exclusion of freezing trials. Results. With auditory pacing present, movement performance was comparable between groups. Following cue withdrawal, motor control deteriorated in those with FOG, resulting in smaller and less stable amplitudes, hastened and more variable frequency, and decreased coordination stability. Conversely, the performance of those without FOG remained mostly similar to that of CTRLs. Conclusions. Compared with those without FOG, those with FOG show greater continuous dyscontrol of bimanual movements, similar to the continuous timing and scaling difficulties during locomotion. Those with FOG also benefit from auditory cueing during upper-limb movements, but these are highly cue dependent. This implies that internal timekeeping functions are more disturbed in those with FOG, who may require rehabilitation strategies for repetitive upper-extremity tasks that include cueing and imagery.

Freezing in Parkinson's disease: a spatiotemporal motor disorder beyond gait.

Freezing of gait (FOG) is an incapacitating problem in Parkinsons disease that is difficult to manage therapeutically. We tested the hypothesis that impaired rhythm and amplitude control is a common mechanism of freezing which is also present during other rhythmic tasks. Therefore, we compared the occurrence and spatiotemporal profiles of freezing episodes during upper limb motion, lower limb motion, and FOG. Eleven freezers, 12 non‐freezers, and 11 controls performed a rhythmic bilateral finger movement task. The triggering effect of movement speed, amplitude, and coordination pattern was evaluated. Regression slopes and spectral analysis addressed the spatial and temporal kinematic changes inherent to freezing episodes. The FOG Questionnaire score significantly predicted severity of upper limb freezing, present in 9 freezers, and of foot freezing, present in 8 freezers. Similar to gait, small‐amplitude movements tended to trigger upper limb freezing, which was preceded by hastened movement and a strong amplitude breakdown. Upper limb freezing power spectra were broadband, including increased energy in the “freeze band” (3–8 Hz). Contrary to FOG, unilateral upper limb freezing was common and occurred mainly on the disease‐dominant side. The findings emphasize that a core motor problem underlies freezing which can affect various movement effectors. This deficit may originate on the disease‐dominant body side and interfere with amplitude and timing regulation during repetitive limb movements. These results may shift current thinking on the origins of freezing as being not exclusively a gait failure.

Explaining freezing of gait in Parkinson's disease: Motor and cognitive determinants

Freezing of gait (FOG) is part of a complex clinical picture in Parkinsons disease (PD) and is largely refractory to standard care. Diverging hypotheses exist about its origins, but a consolidated view on what determines FOG is lacking. The aim of this study was to develop an integrative model of FOG in people with PD. This cross‐sectional study included 51 Parkinson subjects: 24 patients without FOG and 27 with FOG matched for age, gender, and disease severity. Subjects underwent an extensive clinical test battery evaluating general disease characteristics, gait and balance, nongait freezing, and cognitive functions. The relative contribution of these outcomes to FOG was determined using logistic regression analysis. The combination of the following four independent contributors provided the best explanatory model of FOG (R2 = 0.49): nongait freezing; levodopa equivalent dose (LED); cognitive impairment; and falls and balance problems. The model yields a high‐risk profile for FOG (P > 95%) when Parkinson patients are affected by at least one type of nongait freezing (e.g., freezing of other repetitive movements), falls or balance problems during the last 3 months, and a Scales for Outcomes in Parkinsons Disease‐Cognition score below 28. A high LED further increases the risk of FOG to 99%. Nongait freezing, increased dopaminergic drug dose, cognitive deficits, and falls and balance problems are independent determinants of FOG in people with PD and may play a synergistic role in its manifestation.

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 Parkinsons 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.

Impaired implicit sequence learning in Parkinson's disease patients with freezing of gait.

OBJECTIVE Freezing of gait (FOG) in Parkinsons disease (PD) may involve specific impairments in acquiring automaticity under working memory load. This study examined whether implicit sequence learning, with or without a secondary task, is impaired in patients with FOG. METHOD Fourteen freezers (FRs), 14 nonfreezers (nFRs), and 14 matched healthy controls (HCs) performed a serial reaction time (SRT) task with a deterministic stimulus sequence under single-task (ST) and dual-task (DT) conditions. The increase in reaction times (RTs) for random compared with sequenced blocks was used as a measure of implicit sequence learning. Neuropsychological tests assessing global cognitive functioning and executive dysfunction were administered in order to investigate their relation to sequence learning. RESULTS nFRs and HCs showed significant implicit sequence learning effects (p < 0.001). FRs demonstrated a tendency to learn sequence-specific information in the SRT-ST task (p = 0.07) but not in the SRT-DT task (p = 0.69). Severity of FOG, however, correlated positively with SRT-DT task performance (r = -0.56; p < 0.05). CONCLUSIONS The present results suggest that PD patients suffering from FOG pathology exhibit a specific impairment in the acquisition of automaticity. When working memory capacity is supplementarily loaded by adding a DT, sequence learning in FRs becomes increasingly impaired. These findings indicate that therapies should focus on extensive training in acquiring novel motor activities and reducing working memory load to improve learning in FOG.

Does implicit learning in non-demented Parkinson's disease depend on the level of cognitive functioning?

We investigated the influence of the level of cognitive functioning on sequence-specific learning in Parkinsons disease (PD). This was done by examining the relationship between the scales for outcomes in Parkinsons disease-cognition [SCOPA-COG, Marinus, J., Visser, M., Verwey, N. A., Verhey, F. R. J., Middelkoop, H. A. M.,Stiggelbout, A., et al. (2003). Assessment of cognition in Parkinsons disease. Neurology, 61, 1222-1228] and the serial reaction time (SRT) task [Nissen, M. J., & Bullemer, P. T. (1987). Attentional requirements for learning: Evidence from performance measures. Cognitive Psychology, 19, 1-32] in a homogeneous sample, consisting of 25 PD patients diagnosed in Stage 3 of the Hoehn and Yahr [Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: onset, progression, and mortality. Neurology, 17, 427-442] scale. Six patients in the low scoring cognitive group, 11 patients in the average scoring and eight patients in the high scoring group, conducted a SRT task with a deterministic sequence. Sequence-specific learning was assessed by inserting a random block to determine whether the acquisition of sequence movements differed between groups. Our results indicate an association between cognitive functioning in PD patients and sequence learning. These findings emphasize the use of assessing cognition in addition to the well-known motor aspects in PD.