- Email: [email protected]
Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait
Accepted Manuscript Title: MS entitled “Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait” Author: Zacharie Beaulne-S´eguin BSc Julie Nantel PhD PII: DOI: Reference:
S0966-6362(16)30478-7 http://dx.doi.org/doi:10.1016/j.gaitpost.2016.08.002 GAIPOS 5116
To appear in:
Gait & Posture
Received date: Revised date: Accepted date:
26-4-2016 19-7-2016 1-8-2016
Please cite this article as: Beaulne-S´eguin Zacharie, Nantel Julie.MS entitled “Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait”.Gait and Posture http://dx.doi.org/10.1016/j.gaitpost.2016.08.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
MS entitled “Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait”.
Running title: Visual cues lead to error in gait initiation in individuals with freezing of gait.
Zacharie Beaulne-Séguin, BSca, and Julie Nantel, PhDa*, aSchool
of Human Kinetics, Faculty of Health Sciences, Ottawa University, Canada
Financial support: This study was supported by the Parkinson Society Canada Young Investigator Award (JN). This funding source has no involvement in: study design; data collection, analysis and interpretation of data; the writing of the report; and in the decision to submit the article for publication. Conflicts of interest: none Corresponding author: Julie Nantel, PhD., Assistant Professor, School of Human Kinetics Faculty of Health Sciences University of Ottawa 125 rue Université, Pavillon Montpetit, MNT 353 [email protected] Ottawa, Canada, K1N 6N5 Téléphone: 613-562-5800 poste 4025
2
Highlights
We assessed gait initiation following conflicting visual cues in PD
We compared the effect of conflicting visual cues in freezers and non-freezers.
Freezers had restrictive postural strategy and were slower compared to non-freezers.
Conflicting cues led to errors in gait initiation and inhibition in freezers only.
These results were exacerbated in freezers with more severe gait deficits and MCI
3
Abstract Introduction We asked whether conflicting visual cues influences gait initiation, gait inhibition and postural control in Parkinson’s disease (PD) between freezers, non-freezers and healthy older adults. Methods Twenty-five PD participants on dopaminergic medication and 17 healthy older adults were asked to initiate or refrain gait depending on visual cues: green GO (GG), green STOP (GS), red GO (RG), red STOP (RS). Center of pressure (CoP) displacement, variability and mean velocity (VCoP) in the anterior-posterior (AP) and medial-lateral (ML) directions and movement time (MT) were measured. Results Gait initiation: Both freezers and non-freezers were different from controls in GG and GS. In GS, freezers had smaller CoP displacement and velocity in both directions (p<0.01), while non-freezers had smaller VCoP in AP and ML (p<0.01). AP CoP displacement in GS was smaller in freezers compared to non-freezers (p<0.05). Freezers had longer MT compared to controls in GG and compared to both groups in GS (p<0.01). Gait inhibition: Controls and freezers had larger CoP displacement variability (p<0.05) and velocity (p<0.01) in both directions in RG compared to RS. No differences were seen in non-freezers. Three freezers initiated walking during the RG or RS conditions. Conclusion Freezers were in general slower at initiating gait, displayed a more restrictive postural strategy and were more affected by the conflicting conditions compared to both controls and non-freezers. In freezers, the conflicting visual cues may have increased the cognitive load enough to provoke delays in processing the visual information and implementing the appropriate motor program.
4
BACKGROUND Along with turning and walking into narrow spaces such as doorways, gait initiation (GI) is known as one of the main triggers of freezing of gait (FoG). The asymmetric nature of GI and the complex interplay between postural stability and locomotion [1] could explain the highest occurrence of FoG in GI compared to steady state walking. As FoG has been associated with high risks of postural instability, falls and gait asymmetry [2–5], controlling postural stability during GI could interfere with the stepping activity in individuals with FoG. Anticipatory postural adjustments (APAs) are critical to prepare GI, and were reported to be smaller and slower in PD compared to healthy older adults [6,7], due to deficits in posture-locomotion coupling [1,8]. Furthermore, absence of APAs and disruption of spatial-temporal coordination between the APAs and the actual stepping have been associated with FoG [6,8,9]. Cognitive functions also play a main role in GI. Although the underlying mechanisms are still not well understood freezers and individuals with postural instability and gait disturbances may be at higher risks of developing mild cognitive impairments (MCI) as well as dementia compared to tremor dominant individuals [10–13]. FoG has also been strongly associated with deficits in visual-spatial processing and with structural deficits in executive functions, leading to impairments in set-shifting and inhibition function [14–18]. Using incongruous visual cues to assess the effect of age on step response inhibition, Sparto et al., [19,20] showed greater variability, more postural adjustment errors and step initiation latencies in older adults compared to younger adults [19]. The authors suggested that deficits in inhibitory function could affect decision processing and delay voluntary step responses [20]. Cohen et al., [21], reported performance deficits in a Go-No-go task associated with inhibitory control in freezers compared to non-
5 freezers. However, it is not known how conflicting visual cues would affect GI and inhibition in freezers and non-freezers. GI is an insightful model to assess postural mechanisms in older adults and in PD [19,22], and could provide insights regarding the association between postural instability, FoG and MCI in PD. Our main objective is to compare GI and gait inhibition between healthy older adults, freezers and non-freezers when presented with conflicting and non-conflicting visual cues. We expect GI and postural stability in freezers to be more affected, i.e. showing slower GI or increased occurrence of FoG, in the conflicting cues compared to both non-freezers and older adults.
METHODS Twenty-five participants with PD and 17 healthy older adults (age:66.3 sd:9.5, 13 women) participated in the study. PD participants were recruited from the Parkinson's disease and Movement Disorders Clinic of the Ottawa Hospital Research Institute. Inclusion criteria: no history of orthopedic/musculoskeletal impairments, or neurological conditions other then Parkinson’s disease that could impact balance and gait. Testing was performed in the optimally medicated state (dopaminergic medications). PD subjects were divided into freezer (age:69.5, sd:6.2, disease duration: 7.9y, sd:5.3y, n=12, 1 women) and non-freezer (age: 62.9, sd: 10.8, disease duration: 5.4y, sd: 3.8y, n= 13, 2 women) according to the FOG questionnaire. Freezer had to report freezing ‘‘about once a week’’ or more. Controls were excluded if they reported previous surgeries and/or impairments that could interfere with gait and balance. The study was approved by our Institutional Review Board. Participants gave their written consent. PD severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III, (motor disability). Participants performed the Montreal Cognitive Assessment (MoCA) to determine MCI, i.e. scores below 26. Trail-making A and B were performed to assess executive function and cognitive flexibility.
6 Participants stood quietly on a force platform with their feet at a comfortable width and looking straight ahead at a large landscape (3m x 4m) projected on a wall 15m away. Following a visual cue, participants had to promptly initiate walking over 10m or stay quietly on the force platform. Participants were presented with two non-conflicting and two conflicting cues. Adapted from the Stroop Colour and Word test, visual cues were as follow: Green Go (GG), Red Stop (RS), Green Stop (GS) and Red GO (RG). Participants were instructed to start walking when the green signals, GG and GS, were presented, and had to remain on the force platform for 30s when presented with the red signals, RS and RG. Before each trial, participants were asked to “get ready”, after which a 1s to 5s delay was randomly introduced before the projection of the visual cue. The order of the visual cues was randomized and performed twice.
Data acquisition and reduction: Ground reaction forces and moments were collected using one force platform (Kistler, Winterthur, Switzerland) recording at a sampling frequency of 200 Hz. Data were filtered with a zero-lag fourth-order Butterworth filter with a 10Hz cut-off frequency. The time-varying position of the CoP under each foot was calculated using the orthogonal forces and moments on the force plate. The CoP displacement amplitude (in mm), CoP displacement root-mean-square (RMSCoP) and mean velocity (VCoP) (mm/s) were calculated in the anterior-posterior (AP) and medial-lateral (ML) directions. Movement time (MT), from the beginning of the anticipatory postural adjustments (APAs), to the toe off of the trailing leg, was determined for each GI trial.
Statistics: Mixed model for repeated measures were used to determine differences between groups and between conditions for postural stability during the RS and RG trials and for the GIs trials (GG, GS). Bonferroni post-hoc procedures were used. One-way ANOVAs were used to compare age and MoCA scores between the three groups and Student t-test were used to determine any difference for disease duration and UPDRS III between PD.
7
RESULTS Age between the three groups (p=0.21) and disease duration (p=0.20) between freezers and non-freezers were not different, Table 1. UPDRS III (p=0.003), FoG-Q (p<0.001) and trail-making B-A % (p=0.03) were larger in freezers compared to non-freezers. MoCa was lower than 26 in six freezers and two nonfreezers (p=0.07). Five freezers reported one or more falls in the previous 3 months compared to 1 participant in non-freezers (fell once). Two freezers reported falling once, 2 reported falling twice and 1 reported falling three times. Two freezers started walking on the RG signal, one freezer went once on a RS signal and 3 freezers did not go on a GS signal. Non-freezers and controls performed the tasks as instructed.
Gait initiation: CoP displacement amplitude in the ML direction showed no main effect for condition F(1, 35)=.514, p=0.478, while a main effect for group was found F(2, 35)=39.46, p<0.001, Table 2. Multiple comparisons revealed larger CoP displacement amplitude in controls compared to freezers and non-freezers in GG and GS trials p<0.001. No difference was seen between freezers and non-freezers. For the displacement amplitude in the AP direction, an interaction was shown between conditions and groups F(2, 35)=5.441, p=0.009. Multiple comparisons revealed larger displacement amplitude in controls compared to non-freezers in GG (p=0.04) and compared to freezers in GS (p=0.007). In the GS condition non-freezers had larger displacement amplitude compared to freezers (p=0.03). Non-freezers showed larger displacement in GS compared to GG (p=0.03). A main effect for group was seen for VCoP in ML F(2, 35)=18.86, p<0.001. Controls were faster compared to freezers and non-freezers (p<0.001). Controls had larger VCoP compared to freezers in GG (p=0.022) and compared to both groups in GS (p<0.001). No differences were seen between freezers and non-freezers (p=0.110). A main effect for group was found in VCoP AP F(2, 35)=10.88, p<0.001. Multiple comparisons showed faster
8 displacement in controls compared to freezers and non-freezers during the GS trials (p<0.001). No difference was seen between PD participants and no main effect was found for task. Finally, movement time showed a task-group interaction F(2, 35)=3.98, p=0.028. Freezers took more time during GG compared to controls (p<0.001) and a trend was seen compared to non-freezers (p=0.06). Freezers took more time in GS compared to controls (p<0.001) and non-freezers (p=0.002). No difference was seen between non-freezers and controls. Both controls (p=0.01) and freezers (p=0.02) took more time to complete the task in the GS condition. No difference was seen in non-freezers.
Gait inhibition: CoP in ML showed a main effect for task F(1, 37)= 10.163, p=0.003, with controls and freezers displaying smaller displacement variability during RS compared to RG trials (p≤0.05), Table 3. CoP in AP showed effect for both task F(1, 37)=8.624, p=0.006 and group F(2, 37)= 3.779, p=0.032. Controls showed a trend for larger displacement variability compared to non-freezers in RG (p=0.07). No differences were seen between controls and freezers or between freezers and non-freezers. Both controls and freezers had smaller displacement variability in RS compared to RG (p<0.05). VCoP in ML also showed main effects for task F(1, 37)= 8.437, p=0.006 and group F(2, 37)= 4.109, p=0.024, with controls showing a trend for larger velocity compared to non-freezers in RG (p=0.07), but not during the RS or compared to freezers. No difference was seen between freezers and non-freezers. Both controls and freezers had smaller VCoP in RS compared to RG (p<0.05). Finally, VCoP in AP showed a taskgroup interaction F(2, 37)= 3.218, p=0.05. Controls had larger VCoP in RG compared to both freezers and non-freezers (p<0.01). In RS VCoP was also larger in controls compared to freezers (p=0.001) and non-freezers (p=0.05). No difference was seen between freezers and non-freezers. Both controls and freezers had smaller CoP velocity (p<0.01) in RS compared to RG conditions. No differences were seen in non-freezers.
DISCUSSION
9 The objectives were to determine the effect of conflicting visual cues on GI and gait inhibition between freezers, non-freezers and older adults. During the GG condition, freezers showed smaller ML CoP displacement and velocity compared to controls, while displacement and velocity in both ML and AP directions were smaller when presented with conflicting visual cues. In this latter condition, AP CoP displacement was also smaller compared to non-freezers. In non-freezers, the GG led to smaller displacement in the ML and AP directions, while the conflicting condition led to smaller velocity in AP and ML directions compared to controls. Contact time was larger in freezers compared to non-freezers and controls independently of the conditions. As for the gait inhibition conditions, controls and freezers had larger CoP displacement variability and velocity in both directions in the conflicting conditions compared to the non-conflicting condition. Finally, performance errors were seen only in freezers.
Freezers and non-freezers use different postural strategies than controls during GI in both nonconflicting and conflicting conditions The smaller displacement in the medial-lateral direction during GI in PD during the conflicting and non-conflicting condition is in agreement with previous studies [23]. Standing-to-walking transition requests to deliberately disrupt balance to move the center of masse out of the base of support. This requires to closely regulating postural balance to avoid postural instability and allow efficient GI [1,8]. In non-freezer, the smaller CoP displacement suggests that participants might have needed to enhance the control over the center of mass when initiating gait. This is consistent with previous studies reporting that individuals with PD might prioritize postural stability over forward propulsion in tasks involving postural transitions such as GI [1,24]. In freezers, both displacement amplitude and velocity were smaller compared to controls during the non-conflicting condition (GG), but only in the medial-lateral direction. As large displacement and even more so large velocity in the medial-lateral direction have been associated with postural instability and falls in older adults and in individuals with PD [14,25,26],
10 restricting displacement and velocity in this specific direction could have been used in freezers to enhance stability in this direction and thus assure safe forward progression. However, it has been shown that this strategy could in fact increase the risks of falls as it reduces the ability to efficiently modify the motor program when needed, e.g. in response to external or internal disturbances [27]. As the task difficulty increased, the CoP velocity in both directions decreased further potentially to increase postural stability during the conflicting condition.
GI differentiates freezers than non-freezers when presented with conflicting visual cues. GI during the conflicting condition was even more closely regulated in freezers, with displacement and velocity in both directions being smaller compared to controls and displacement in the AP direction discriminating between freezers and non-freezers. Furthermore, freezers took more time to complete GI compared to both controls and non-freezers in both non-conflicting and conflicting conditions. They also took more time during the conflicting condition compared to the non-conflicting condition. As GI is one of the main triggers of FoG, the larger time to complete the task in freezers could have been indicative of FoG. However, none of the participants reported freezing during the protocol. This was confirmed as none of the typical characteristics of freezing episodes, such as repeated and incomplete load-unload or trembling of the leg [3–5,9,14], were detected visually or on the force platform. Therefore, this results may be mostly attributable to freezers being slower to complete the motor program, but also slower to process the visual cues and select the appropriate motor program, especially in the conflicting conditions. These results are similar to those by Uemera et al., [28] who reported longer time to process incongruent visual information, generate the adequate motor program and a larger number of errors in the motor program when presented with incongruent in young adults. However, freezers might have been more affected by the conflicting visual cues compared to both nonfreezers and controls. It was previously reported that deficits in visuospatial processing and reasoning could differentiate between freezers from non-freezers [14]. Therefore, in presence of conflicting visual
11 cues, freezers may necessitate a more restrictive postural strategy to assure postural balance while processing the conflicting visual information and generating the appropriate motor pattern. However, the present protocol does not allow distinguishing between the specific impact of deficits in visuospatial processing and the overall cognitive functions. Despite that disease duration was not significantly different between the PD groups, Trail Making B-A and the MOCA scores were in average poorer in freezers. The Trail making B-A is one of the most common tests used to assess executive functions. Cognitive abilities such as attention, visual search, abstraction, shifting and flexibility are also needed to succeed in completing the task. In freezers, different deficits in the cognitive functions may have led to the longer response time and occurrence of errors during GI and especially when the motor program had to be modified according to the conflicting visual cues. Furthermore, six individuals had a MoCA score below 26 compared to two in the nonfreezers group. This could account for the larger number of errors displayed in freezers when provided with the conflicting cues, as two of the three participants that did not go on the GS signal had a MOCA score below the threshold for MCI. However, three of the participants in the freezer group and two in the non-freezer group with lower MOCA scores were able to perform the task as instructed, which suggests that other variables need to be taken into account to explain failure to perform the tasks successfully.
Freezers have difficulties inhibiting gait when presented with conflicting visual cues Both controls and freezers had larger CoP displacement and velocity in the conflicting gait inhibition condition compared to the non-conflicting condition. Participants in these two groups may have chosen to implement the motor program for GI independently of the cues presented and inhibited it when necessary. This postural strategy seems appropriate in healthy individuals that can efficiently modify the motor program. However, the occurrence of errors in freezers is indicative of an inability to efficiently modify the motor program when gait as to be inhibited, especially in those with more important gait deficits and/or MCI. It has been suggested that deficits in inhibitory functions could be responsible for
12 increasing time to complete the first step during GI and larger number of errors in postural responses when multiple stimulus-response possibilities are presented [19]. The number of errors in the freezer group in GI, but also in condition when gait had to be inhibited may illustrate a greater deficit in inhibition function in freezers compared to non-freezers as previously reported [21]. Furthermore, our results emphasized the impact of cognitive dysfunctions in generating incorrect motor program when presented with conflicting visual cues, and during non-conflicting visual cues when different options were possible. However, it is difficult to determine which of the inhibitory or visual-processing dysfunctions were mainly responsible for the errors in freezers. Non-freezers did not show difference in postural control during the gait inhibition conditions. Non-freezers may have selected a more conservative postural strategy that provided them the appropriate amount of time to process the visual information and select the appropriate motor response. This strategy could have allowed them to minimize the number of errors, while still efficiently initiating gait.
Conclusion Overall, during GI freezers used a more restrictive postural strategy and were slower compared to both controls and non-freezers. Freezers were also slower to initiate gait during the conflicting condition compared to the non-conflicting condition and only participants in this group implemented inappropriate motor programs both during GI and gait inhibition. Individuals with FoG may have been slower at processing the visual information and implementing the appropriate motor program, which is consistent with presence of cognitive impairments in this group. Similarly to controls but contrary to non-freezers, freezers had larger displacement and velocity during the conflicting condition when gait had to be inhibited, which suggests that they could have been preparing to initiate gait independently of the cue and modify the motor response when needed. However, the occurrence of errors in freezers is indicative of an inability to efficiently modify the motor program when the visual cue was different from expected
13 and may worsened in individuals with gait deficits and MCI. This information is important when developing rehabilitation programs to improve functional mobility in PD. Programs targeting the overall postural stability could be indicated in both freezers and non-freezers. However, special attention to improving the ability to implement adequate postural strategies in challenging contexts could be particularly relevant in individuals with FoG, as flexibility in adapting postural strategy may be determinant in preventing falls.
Funding This work was supported by the Parkinson Society Canada, Young Investigator award (JN). Conflict of interest statement The authors declare no conflicts of interest.
14
Reference list. [1]
M.-L. Mille, M. Simoneau, M.W. Rogers, Postural dependence of human locomotion during gait initiation., J. Neurophysiol. 112 (2014) 3095–103. doi:10.1152/jn.00436.2014.
[2]
J. Nantel, H. Bronte-Stewart, The effect of medication and the role of postural instability in different components of freezing of gait (FOG), Parkinsonism Relat. Disord. 20 (2014) 447–451. doi:10.1016/j.parkreldis.2014.01.017.
[3]
J. Nantel, C. de Solages, H. Bronte-Stewart, Repetitive stepping in place identifies and measures freezing episodes in subjects with Parkinson’s disease, Gait Posture. 34 (2011) 329–333. doi:10.1016/j.gaitpost.2011.05.020.
[4]
J.M. Hausdorff, J.D. Schaafsma, Y. Balash, a L. Bartels, T. Gurevich, N. Giladi, Impaired regulation of stride variability in Parkinson’s disease subjects with freezing of gait., Exp. Brain Res. 149 (2003) 187–94. doi:10.1007/s00221-002-1354-8.
[5]
M. Plotnik, N. Giladi, Y. Balash, C. Peretz, J.M. Hausdorff, Is freezing of gait in Parkinson’s disease related to asymmetric motor function?, Ann. Neurol. 57 (2005) 656–663. doi:10.1002/ana.20452.
[6]
A. Burleigh-Jacobs, F.B. Horak, J.G. Nutt, J.A. Obeso, Step initiation in Parkinson’s disease: Influence of levodopa and external sensory triggers, Mov. Disord. 12 (1997) 206–215. doi:10.1002/mds.870120211.
[7]
M. Vaugoyeau, F. Viallet, S. Mesure, J. Massion, Coordination of axial rotation and step execution: Deficits in Parkinson’s disease, Gait Posture. 18 (2003) 150–157. doi:10.1016/S09666362(03)00034-1.
[8]
M.L. Mille, R.A. Creath, M.G. Prettyman, M. Johnson Hilliard, K.M. Martinez, C.D. MacKinnon, et al., Posture and locomotion coupling: A target for rehabilitation interventions in persons with Parkinson’s disease, Parkinsons. Dis. 2012 (2012). doi:10.1155/2012/754186.
15 [9]
J. V. Jacobs, J.G. Nutt, P. Carlson-Kuhta, M. Stephens, F.B. Horak, Knee trembling during freezing of gait represents multiple anticipatory postural adjustments, Exp. Neurol. 215 (2009) 334–341. doi:10.1016/j.expneurol.2008.10.019.
[10]
J.-P. Taylor, E.N. Rowan, D. Lett, J.T. O’Brien, I.G. McKeith, D.J. Burn, Poor attentional function predicts cognitive decline in patients with non-demented Parkinson’s disease independent of motor phenotype., J. Neurol. Neurosurg. Psychiatry. 79 (2008) 1318–1323. doi:10.1136/jnnp.2008.147629.
[11]
G. Alves, J.P. Larsen, M. Emre, T. Wentzel-Larsen, D. Aarsland, Changes in motor subtype and risk for incident dementia in Parkinson’s disease, Mov. Disord. 21 (2006) 1123–1130. doi:10.1002/mds.20897.
[12]
D.J. Burn, E.N. Rowan, L.M. Allan, S. Molloy, J.T. O’Brien, I.G. McKeith, Motor subtype and cognitive decline in Parkinson’s disease, Parkinson's disease with dementia, and dementia with Lewy bodies., J. Neurol. Neurosurg. Psychiatry. 77 (2006) 585–589. doi:10.1136/jnnp.2005.081711.
[13]
G. Vervoort, A. Bengevoord, E. Nackaerts, E. Heremans, W. Vandenberghe, A. Nieuwboer, Distal motor deficit contributions to postural instability and gait disorder in Parkinson’s disease, Behav. Brain Res. 287 (2015) 1–7. doi:10.1016/j.bbr.2015.03.026.
[14]
J. Nantel, J.C. McDonald, S. Tan, H. Bronte-Stewart, Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson’s disease, Neuroscience. 221 (2012) 151–156. doi:10.1016/j.neuroscience.2012.07.007.
[15]
R.G. Cohen, A. Chao, J.G. Nutt, F.B. Horak, Freezing of gait is associated with a mismatch between motor imagery and motor execution in narrow doorways, not with failure to judge doorway passability, Neuropsychologia. 49 (2011) 3981–3988. doi:10.1016/j.neuropsychologia.2011.10.014.
[16]
Q.J. Almeida, C.A. Lebold, Freezing of gait in Parkinson’s disease: a perceptual cause for a motor
16 impairment?, J. Neurol. Neurosurg. Psychiatry. 81 (2010) 513–8. doi:10.1136/jnnp.2008.160580. [17]
D. Cowie, P. Limousin, A. Peters, B.L. Day, Insights into the neural control of locomotion from walking through doorways in Parkinson’s disease, Neuropsychologia. 48 (2010) 2750–2757. doi:10.1016/j.neuropsychologia.2010.05.022.
[18]
S.L. Naismith, J.M. Shine, S.J.G. Lewis, The specific contributions of set-shifting to freezing of gait in Parkinson’s disease, Mov. Disord. 25 (2010) 1000–1004. doi:10.1002/mds.23005.
[19]
P.J. Sparto, S.I. Fuhrman, M.S. Redfern, S. Perera, J.R. Jennings, J.M. Furman, Postural adjustment errors during lateral step initiation in older and younger adults, Exp. Brain Res. 232 (2014) 3977–3989. doi:10.1007/s00221-014-4081-z.
[20]
P.J. Sparto, S.I. Fuhrman, M.S. Redfern, S. Perera, J.R. Jennings, R.D. Nebes, et al., Postural adjustment errors reveal deficits in inhibition during lateral step initiation in older adults, J. Neurophysiol. 109 (2013) 415–428.
[21]
R.G. Cohen, A.K. Klein, M. Nomurab, M. Fleming, M. Mancini, N. Giladi, et al., Inhibition, Executive Function, and Freezing of Gait, J. Pakinsons Disord. 4 (2014) 111–122. doi:10.3233/JPD-130221.
[22]
A. Delval, C. Tard, L. Defebvre, Why we should study gait initiation in Parkinson’s disease, Neurophysiol. Clin. 44 (2014) 69–76. doi:10.1016/j.neucli.2013.10.127.
[23]
J.R. Nocera, R. Roemmich, J. Elrod, L.J.P. Altmann, C.J. Hass, Effects of cognitive task on gait initiation in Parkinson disease: evidence of motor prioritization?, J. Rehabil. Res. Dev. 50 (2013) 699–708. doi:http://dx.doi.org/10.1682/JRRD.2012.06.0114.
[24]
S. Vallabhajosula, T.A. Buckley, M.D. Tillman, C.J. Hass, Age and Parkinson’s disease related kinematic alterations during multi-directional gait initiation, Gait Posture. 37 (2013) 280–286. doi:10.1016/j.gaitpost.2012.07.018.
[25]
B.E. Maki, W.E. McIlroy, Control of rapid limb movements for balance recovery: Age-related changes and implications for fall prevention, Age Ageing. 35 (2006) 12–18.
17 doi:10.1093/ageing/afl078. [26]
R. Sciadas, C. Dalton, J. Nantel, Effort to reduce postural sway affects both cognitive and motor performances in individuals with Parkinson’s disease, Hum. Mov. Sci. (2016) 135–140.
[27]
J.D. Holmes, M.E. Jenkins, A.M. Johnson, S.G. Adams, S.J. Spaulding, Dual-task interference: the effects of verbal cognitive tasks on upright postural stability in Parkinson’s disease., Parkinsons. Dis. 2010 (2010) 696492. doi:10.4061/2010/696492.
[28]
K. Uemura, T. Oya, Y. Uchiyama, Effects of visual interference on initial motor program errors and execution times in the choice step reaction, Gait Posture. 38 (2013) 68–72. doi:10.1016/j.gaitpost.2012.10.016.
18
19
Table 1 Freezing of gait (FoG) questionnaire, Montreal Cognitive Assessment (MoCA) and Trail Making B-A in freezers and non-freezers
FoG questionnaire MoCA Trail making B-A (s) Trail making B-A (%)
Non-Freezers 1.0 ± 1.0 27.0 ± 1.7 29 ± 23 201 ± 69.1
† Significantly different, p <0.05
Freezers 9.7 ± 5.1† 25.3 ± 3.4 70.3 ± 54.2 286.3 ± 134.4
P values 0.000 0.071 0.026 0.066
20
Table 2 Center of pressure (CoP) displacement amplitude (mm) and CoP velocity (mm/s) in the medial-lateral (ML) and anterior-posterior directions for Controls and individuals with Parkinson’s disease (PD) during the Green Go and Green Stop trials. Green Go ML 2.85 ± 0.54
Controls Green Stop 2.76 ± 0.48
Non-Freezers Green Go Green Stop 1.46 ± 0.40 † 1.43 ± 0.30 †
Freezers Green Go Green Stop 1.76 ± 0.77 † 1.76 ± 0.47 †
Range CoP (mm) 2.35 ± 0.45
2.28 ± 0.35
1.88 ± 0.31
*† 2.21 ± 0.50
ML 1.60 ± 0.44
1.62 ± 0.98
0.86 ± 1.25
0.23 ± 0.17
AP
1.28 ± 0.57
1.02 ± 1.36
0.42 ± 0.31
Contact (s) 2.33 ± 0.17 * 2.49 ± 0.28 † Significantly different from Controls ‡ Significantly different from non-freezers * GS different from GG p <0.05
2.51 ± 0.23
2.61 ± 0.32
AP
1.97 ± 0.66
1.74 ± 0.34 ‡†
†
0.69 ± 0.79 †
0.26 ± 0.16 †
†
0.78 ± 0.84
0.33 ± 0.19 †
Speed (mm/s) 1.52 ± 0.78
2.74 ± 0.31 *† 3.81 ± 1.4
‡†
21
Table 3 Center of pressure (CoP) root mean square (RMS) displacement (mm) and CoP velocity (mm/s) for Controls, non-freezers and freezers.
ML
Controls Red GO Red STOP 7.55 ± 6.03 5.02 ± 2.70*
Non-Freezers Red GO Red STOP 5.24 ± 2.96 4.70 ± 2.17
Freezers Red GO Red STOP 6.64 ± 4.06 3.60 ± 1.33*
AP
11.37 ± 6.71
76.35 ± 2.34*
6.98 ± 2.51
6.99 ± 2.69
7.93 ± 3.28
6.03 ± 2.17*
ML 11.40 ± 8.42
69.47 ± 2.98*
6.23 ± 32.59
6.09 ± 2.86
7.10 ± 2.68
4.78 ± 1.81*
AP 16.82 ± 7.10 11.98 ± 3.09* † Significantly different from Controls * GS different from GG p <0.05
9.38 ± 3.37†
9.41 ±3.27†
10.24 ± 2.89†
7.54 ± 2.11*†
CoP (mm)
VCoP (mm/s)
S0966-6362(16)30478-7 http://dx.doi.org/doi:10.1016/j.gaitpost.2016.08.002 GAIPOS 5116
To appear in:
Gait & Posture
Received date: Revised date: Accepted date:
26-4-2016 19-7-2016 1-8-2016
Please cite this article as: Beaulne-S´eguin Zacharie, Nantel Julie.MS entitled “Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait”.Gait and Posture http://dx.doi.org/10.1016/j.gaitpost.2016.08.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
MS entitled “Conflicting and non-conflicting visual cues lead to error in gait initiation and gait inhibition in individuals with freezing of gait”.
Running title: Visual cues lead to error in gait initiation in individuals with freezing of gait.
Zacharie Beaulne-Séguin, BSca, and Julie Nantel, PhDa*, aSchool
of Human Kinetics, Faculty of Health Sciences, Ottawa University, Canada
Financial support: This study was supported by the Parkinson Society Canada Young Investigator Award (JN). This funding source has no involvement in: study design; data collection, analysis and interpretation of data; the writing of the report; and in the decision to submit the article for publication. Conflicts of interest: none Corresponding author: Julie Nantel, PhD., Assistant Professor, School of Human Kinetics Faculty of Health Sciences University of Ottawa 125 rue Université, Pavillon Montpetit, MNT 353 [email protected] Ottawa, Canada, K1N 6N5 Téléphone: 613-562-5800 poste 4025
2
Highlights
We assessed gait initiation following conflicting visual cues in PD
We compared the effect of conflicting visual cues in freezers and non-freezers.
Freezers had restrictive postural strategy and were slower compared to non-freezers.
Conflicting cues led to errors in gait initiation and inhibition in freezers only.
These results were exacerbated in freezers with more severe gait deficits and MCI
3
Abstract Introduction We asked whether conflicting visual cues influences gait initiation, gait inhibition and postural control in Parkinson’s disease (PD) between freezers, non-freezers and healthy older adults. Methods Twenty-five PD participants on dopaminergic medication and 17 healthy older adults were asked to initiate or refrain gait depending on visual cues: green GO (GG), green STOP (GS), red GO (RG), red STOP (RS). Center of pressure (CoP) displacement, variability and mean velocity (VCoP) in the anterior-posterior (AP) and medial-lateral (ML) directions and movement time (MT) were measured. Results Gait initiation: Both freezers and non-freezers were different from controls in GG and GS. In GS, freezers had smaller CoP displacement and velocity in both directions (p<0.01), while non-freezers had smaller VCoP in AP and ML (p<0.01). AP CoP displacement in GS was smaller in freezers compared to non-freezers (p<0.05). Freezers had longer MT compared to controls in GG and compared to both groups in GS (p<0.01). Gait inhibition: Controls and freezers had larger CoP displacement variability (p<0.05) and velocity (p<0.01) in both directions in RG compared to RS. No differences were seen in non-freezers. Three freezers initiated walking during the RG or RS conditions. Conclusion Freezers were in general slower at initiating gait, displayed a more restrictive postural strategy and were more affected by the conflicting conditions compared to both controls and non-freezers. In freezers, the conflicting visual cues may have increased the cognitive load enough to provoke delays in processing the visual information and implementing the appropriate motor program.
4
BACKGROUND Along with turning and walking into narrow spaces such as doorways, gait initiation (GI) is known as one of the main triggers of freezing of gait (FoG). The asymmetric nature of GI and the complex interplay between postural stability and locomotion [1] could explain the highest occurrence of FoG in GI compared to steady state walking. As FoG has been associated with high risks of postural instability, falls and gait asymmetry [2–5], controlling postural stability during GI could interfere with the stepping activity in individuals with FoG. Anticipatory postural adjustments (APAs) are critical to prepare GI, and were reported to be smaller and slower in PD compared to healthy older adults [6,7], due to deficits in posture-locomotion coupling [1,8]. Furthermore, absence of APAs and disruption of spatial-temporal coordination between the APAs and the actual stepping have been associated with FoG [6,8,9]. Cognitive functions also play a main role in GI. Although the underlying mechanisms are still not well understood freezers and individuals with postural instability and gait disturbances may be at higher risks of developing mild cognitive impairments (MCI) as well as dementia compared to tremor dominant individuals [10–13]. FoG has also been strongly associated with deficits in visual-spatial processing and with structural deficits in executive functions, leading to impairments in set-shifting and inhibition function [14–18]. Using incongruous visual cues to assess the effect of age on step response inhibition, Sparto et al., [19,20] showed greater variability, more postural adjustment errors and step initiation latencies in older adults compared to younger adults [19]. The authors suggested that deficits in inhibitory function could affect decision processing and delay voluntary step responses [20]. Cohen et al., [21], reported performance deficits in a Go-No-go task associated with inhibitory control in freezers compared to non-
5 freezers. However, it is not known how conflicting visual cues would affect GI and inhibition in freezers and non-freezers. GI is an insightful model to assess postural mechanisms in older adults and in PD [19,22], and could provide insights regarding the association between postural instability, FoG and MCI in PD. Our main objective is to compare GI and gait inhibition between healthy older adults, freezers and non-freezers when presented with conflicting and non-conflicting visual cues. We expect GI and postural stability in freezers to be more affected, i.e. showing slower GI or increased occurrence of FoG, in the conflicting cues compared to both non-freezers and older adults.
METHODS Twenty-five participants with PD and 17 healthy older adults (age:66.3 sd:9.5, 13 women) participated in the study. PD participants were recruited from the Parkinson's disease and Movement Disorders Clinic of the Ottawa Hospital Research Institute. Inclusion criteria: no history of orthopedic/musculoskeletal impairments, or neurological conditions other then Parkinson’s disease that could impact balance and gait. Testing was performed in the optimally medicated state (dopaminergic medications). PD subjects were divided into freezer (age:69.5, sd:6.2, disease duration: 7.9y, sd:5.3y, n=12, 1 women) and non-freezer (age: 62.9, sd: 10.8, disease duration: 5.4y, sd: 3.8y, n= 13, 2 women) according to the FOG questionnaire. Freezer had to report freezing ‘‘about once a week’’ or more. Controls were excluded if they reported previous surgeries and/or impairments that could interfere with gait and balance. The study was approved by our Institutional Review Board. Participants gave their written consent. PD severity was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III, (motor disability). Participants performed the Montreal Cognitive Assessment (MoCA) to determine MCI, i.e. scores below 26. Trail-making A and B were performed to assess executive function and cognitive flexibility.
6 Participants stood quietly on a force platform with their feet at a comfortable width and looking straight ahead at a large landscape (3m x 4m) projected on a wall 15m away. Following a visual cue, participants had to promptly initiate walking over 10m or stay quietly on the force platform. Participants were presented with two non-conflicting and two conflicting cues. Adapted from the Stroop Colour and Word test, visual cues were as follow: Green Go (GG), Red Stop (RS), Green Stop (GS) and Red GO (RG). Participants were instructed to start walking when the green signals, GG and GS, were presented, and had to remain on the force platform for 30s when presented with the red signals, RS and RG. Before each trial, participants were asked to “get ready”, after which a 1s to 5s delay was randomly introduced before the projection of the visual cue. The order of the visual cues was randomized and performed twice.
Data acquisition and reduction: Ground reaction forces and moments were collected using one force platform (Kistler, Winterthur, Switzerland) recording at a sampling frequency of 200 Hz. Data were filtered with a zero-lag fourth-order Butterworth filter with a 10Hz cut-off frequency. The time-varying position of the CoP under each foot was calculated using the orthogonal forces and moments on the force plate. The CoP displacement amplitude (in mm), CoP displacement root-mean-square (RMSCoP) and mean velocity (VCoP) (mm/s) were calculated in the anterior-posterior (AP) and medial-lateral (ML) directions. Movement time (MT), from the beginning of the anticipatory postural adjustments (APAs), to the toe off of the trailing leg, was determined for each GI trial.
Statistics: Mixed model for repeated measures were used to determine differences between groups and between conditions for postural stability during the RS and RG trials and for the GIs trials (GG, GS). Bonferroni post-hoc procedures were used. One-way ANOVAs were used to compare age and MoCA scores between the three groups and Student t-test were used to determine any difference for disease duration and UPDRS III between PD.
7
RESULTS Age between the three groups (p=0.21) and disease duration (p=0.20) between freezers and non-freezers were not different, Table 1. UPDRS III (p=0.003), FoG-Q (p<0.001) and trail-making B-A % (p=0.03) were larger in freezers compared to non-freezers. MoCa was lower than 26 in six freezers and two nonfreezers (p=0.07). Five freezers reported one or more falls in the previous 3 months compared to 1 participant in non-freezers (fell once). Two freezers reported falling once, 2 reported falling twice and 1 reported falling three times. Two freezers started walking on the RG signal, one freezer went once on a RS signal and 3 freezers did not go on a GS signal. Non-freezers and controls performed the tasks as instructed.
Gait initiation: CoP displacement amplitude in the ML direction showed no main effect for condition F(1, 35)=.514, p=0.478, while a main effect for group was found F(2, 35)=39.46, p<0.001, Table 2. Multiple comparisons revealed larger CoP displacement amplitude in controls compared to freezers and non-freezers in GG and GS trials p<0.001. No difference was seen between freezers and non-freezers. For the displacement amplitude in the AP direction, an interaction was shown between conditions and groups F(2, 35)=5.441, p=0.009. Multiple comparisons revealed larger displacement amplitude in controls compared to non-freezers in GG (p=0.04) and compared to freezers in GS (p=0.007). In the GS condition non-freezers had larger displacement amplitude compared to freezers (p=0.03). Non-freezers showed larger displacement in GS compared to GG (p=0.03). A main effect for group was seen for VCoP in ML F(2, 35)=18.86, p<0.001. Controls were faster compared to freezers and non-freezers (p<0.001). Controls had larger VCoP compared to freezers in GG (p=0.022) and compared to both groups in GS (p<0.001). No differences were seen between freezers and non-freezers (p=0.110). A main effect for group was found in VCoP AP F(2, 35)=10.88, p<0.001. Multiple comparisons showed faster
8 displacement in controls compared to freezers and non-freezers during the GS trials (p<0.001). No difference was seen between PD participants and no main effect was found for task. Finally, movement time showed a task-group interaction F(2, 35)=3.98, p=0.028. Freezers took more time during GG compared to controls (p<0.001) and a trend was seen compared to non-freezers (p=0.06). Freezers took more time in GS compared to controls (p<0.001) and non-freezers (p=0.002). No difference was seen between non-freezers and controls. Both controls (p=0.01) and freezers (p=0.02) took more time to complete the task in the GS condition. No difference was seen in non-freezers.
Gait inhibition: CoP in ML showed a main effect for task F(1, 37)= 10.163, p=0.003, with controls and freezers displaying smaller displacement variability during RS compared to RG trials (p≤0.05), Table 3. CoP in AP showed effect for both task F(1, 37)=8.624, p=0.006 and group F(2, 37)= 3.779, p=0.032. Controls showed a trend for larger displacement variability compared to non-freezers in RG (p=0.07). No differences were seen between controls and freezers or between freezers and non-freezers. Both controls and freezers had smaller displacement variability in RS compared to RG (p<0.05). VCoP in ML also showed main effects for task F(1, 37)= 8.437, p=0.006 and group F(2, 37)= 4.109, p=0.024, with controls showing a trend for larger velocity compared to non-freezers in RG (p=0.07), but not during the RS or compared to freezers. No difference was seen between freezers and non-freezers. Both controls and freezers had smaller VCoP in RS compared to RG (p<0.05). Finally, VCoP in AP showed a taskgroup interaction F(2, 37)= 3.218, p=0.05. Controls had larger VCoP in RG compared to both freezers and non-freezers (p<0.01). In RS VCoP was also larger in controls compared to freezers (p=0.001) and non-freezers (p=0.05). No difference was seen between freezers and non-freezers. Both controls and freezers had smaller CoP velocity (p<0.01) in RS compared to RG conditions. No differences were seen in non-freezers.
DISCUSSION
9 The objectives were to determine the effect of conflicting visual cues on GI and gait inhibition between freezers, non-freezers and older adults. During the GG condition, freezers showed smaller ML CoP displacement and velocity compared to controls, while displacement and velocity in both ML and AP directions were smaller when presented with conflicting visual cues. In this latter condition, AP CoP displacement was also smaller compared to non-freezers. In non-freezers, the GG led to smaller displacement in the ML and AP directions, while the conflicting condition led to smaller velocity in AP and ML directions compared to controls. Contact time was larger in freezers compared to non-freezers and controls independently of the conditions. As for the gait inhibition conditions, controls and freezers had larger CoP displacement variability and velocity in both directions in the conflicting conditions compared to the non-conflicting condition. Finally, performance errors were seen only in freezers.
Freezers and non-freezers use different postural strategies than controls during GI in both nonconflicting and conflicting conditions The smaller displacement in the medial-lateral direction during GI in PD during the conflicting and non-conflicting condition is in agreement with previous studies [23]. Standing-to-walking transition requests to deliberately disrupt balance to move the center of masse out of the base of support. This requires to closely regulating postural balance to avoid postural instability and allow efficient GI [1,8]. In non-freezer, the smaller CoP displacement suggests that participants might have needed to enhance the control over the center of mass when initiating gait. This is consistent with previous studies reporting that individuals with PD might prioritize postural stability over forward propulsion in tasks involving postural transitions such as GI [1,24]. In freezers, both displacement amplitude and velocity were smaller compared to controls during the non-conflicting condition (GG), but only in the medial-lateral direction. As large displacement and even more so large velocity in the medial-lateral direction have been associated with postural instability and falls in older adults and in individuals with PD [14,25,26],
10 restricting displacement and velocity in this specific direction could have been used in freezers to enhance stability in this direction and thus assure safe forward progression. However, it has been shown that this strategy could in fact increase the risks of falls as it reduces the ability to efficiently modify the motor program when needed, e.g. in response to external or internal disturbances [27]. As the task difficulty increased, the CoP velocity in both directions decreased further potentially to increase postural stability during the conflicting condition.
GI differentiates freezers than non-freezers when presented with conflicting visual cues. GI during the conflicting condition was even more closely regulated in freezers, with displacement and velocity in both directions being smaller compared to controls and displacement in the AP direction discriminating between freezers and non-freezers. Furthermore, freezers took more time to complete GI compared to both controls and non-freezers in both non-conflicting and conflicting conditions. They also took more time during the conflicting condition compared to the non-conflicting condition. As GI is one of the main triggers of FoG, the larger time to complete the task in freezers could have been indicative of FoG. However, none of the participants reported freezing during the protocol. This was confirmed as none of the typical characteristics of freezing episodes, such as repeated and incomplete load-unload or trembling of the leg [3–5,9,14], were detected visually or on the force platform. Therefore, this results may be mostly attributable to freezers being slower to complete the motor program, but also slower to process the visual cues and select the appropriate motor program, especially in the conflicting conditions. These results are similar to those by Uemera et al., [28] who reported longer time to process incongruent visual information, generate the adequate motor program and a larger number of errors in the motor program when presented with incongruent in young adults. However, freezers might have been more affected by the conflicting visual cues compared to both nonfreezers and controls. It was previously reported that deficits in visuospatial processing and reasoning could differentiate between freezers from non-freezers [14]. Therefore, in presence of conflicting visual
11 cues, freezers may necessitate a more restrictive postural strategy to assure postural balance while processing the conflicting visual information and generating the appropriate motor pattern. However, the present protocol does not allow distinguishing between the specific impact of deficits in visuospatial processing and the overall cognitive functions. Despite that disease duration was not significantly different between the PD groups, Trail Making B-A and the MOCA scores were in average poorer in freezers. The Trail making B-A is one of the most common tests used to assess executive functions. Cognitive abilities such as attention, visual search, abstraction, shifting and flexibility are also needed to succeed in completing the task. In freezers, different deficits in the cognitive functions may have led to the longer response time and occurrence of errors during GI and especially when the motor program had to be modified according to the conflicting visual cues. Furthermore, six individuals had a MoCA score below 26 compared to two in the nonfreezers group. This could account for the larger number of errors displayed in freezers when provided with the conflicting cues, as two of the three participants that did not go on the GS signal had a MOCA score below the threshold for MCI. However, three of the participants in the freezer group and two in the non-freezer group with lower MOCA scores were able to perform the task as instructed, which suggests that other variables need to be taken into account to explain failure to perform the tasks successfully.
Freezers have difficulties inhibiting gait when presented with conflicting visual cues Both controls and freezers had larger CoP displacement and velocity in the conflicting gait inhibition condition compared to the non-conflicting condition. Participants in these two groups may have chosen to implement the motor program for GI independently of the cues presented and inhibited it when necessary. This postural strategy seems appropriate in healthy individuals that can efficiently modify the motor program. However, the occurrence of errors in freezers is indicative of an inability to efficiently modify the motor program when gait as to be inhibited, especially in those with more important gait deficits and/or MCI. It has been suggested that deficits in inhibitory functions could be responsible for
12 increasing time to complete the first step during GI and larger number of errors in postural responses when multiple stimulus-response possibilities are presented [19]. The number of errors in the freezer group in GI, but also in condition when gait had to be inhibited may illustrate a greater deficit in inhibition function in freezers compared to non-freezers as previously reported [21]. Furthermore, our results emphasized the impact of cognitive dysfunctions in generating incorrect motor program when presented with conflicting visual cues, and during non-conflicting visual cues when different options were possible. However, it is difficult to determine which of the inhibitory or visual-processing dysfunctions were mainly responsible for the errors in freezers. Non-freezers did not show difference in postural control during the gait inhibition conditions. Non-freezers may have selected a more conservative postural strategy that provided them the appropriate amount of time to process the visual information and select the appropriate motor response. This strategy could have allowed them to minimize the number of errors, while still efficiently initiating gait.
Conclusion Overall, during GI freezers used a more restrictive postural strategy and were slower compared to both controls and non-freezers. Freezers were also slower to initiate gait during the conflicting condition compared to the non-conflicting condition and only participants in this group implemented inappropriate motor programs both during GI and gait inhibition. Individuals with FoG may have been slower at processing the visual information and implementing the appropriate motor program, which is consistent with presence of cognitive impairments in this group. Similarly to controls but contrary to non-freezers, freezers had larger displacement and velocity during the conflicting condition when gait had to be inhibited, which suggests that they could have been preparing to initiate gait independently of the cue and modify the motor response when needed. However, the occurrence of errors in freezers is indicative of an inability to efficiently modify the motor program when the visual cue was different from expected
13 and may worsened in individuals with gait deficits and MCI. This information is important when developing rehabilitation programs to improve functional mobility in PD. Programs targeting the overall postural stability could be indicated in both freezers and non-freezers. However, special attention to improving the ability to implement adequate postural strategies in challenging contexts could be particularly relevant in individuals with FoG, as flexibility in adapting postural strategy may be determinant in preventing falls.
Funding This work was supported by the Parkinson Society Canada, Young Investigator award (JN). Conflict of interest statement The authors declare no conflicts of interest.
14
Reference list. [1]
M.-L. Mille, M. Simoneau, M.W. Rogers, Postural dependence of human locomotion during gait initiation., J. Neurophysiol. 112 (2014) 3095–103. doi:10.1152/jn.00436.2014.
[2]
J. Nantel, H. Bronte-Stewart, The effect of medication and the role of postural instability in different components of freezing of gait (FOG), Parkinsonism Relat. Disord. 20 (2014) 447–451. doi:10.1016/j.parkreldis.2014.01.017.
[3]
J. Nantel, C. de Solages, H. Bronte-Stewart, Repetitive stepping in place identifies and measures freezing episodes in subjects with Parkinson’s disease, Gait Posture. 34 (2011) 329–333. doi:10.1016/j.gaitpost.2011.05.020.
[4]
J.M. Hausdorff, J.D. Schaafsma, Y. Balash, a L. Bartels, T. Gurevich, N. Giladi, Impaired regulation of stride variability in Parkinson’s disease subjects with freezing of gait., Exp. Brain Res. 149 (2003) 187–94. doi:10.1007/s00221-002-1354-8.
[5]
M. Plotnik, N. Giladi, Y. Balash, C. Peretz, J.M. Hausdorff, Is freezing of gait in Parkinson’s disease related to asymmetric motor function?, Ann. Neurol. 57 (2005) 656–663. doi:10.1002/ana.20452.
[6]
A. Burleigh-Jacobs, F.B. Horak, J.G. Nutt, J.A. Obeso, Step initiation in Parkinson’s disease: Influence of levodopa and external sensory triggers, Mov. Disord. 12 (1997) 206–215. doi:10.1002/mds.870120211.
[7]
M. Vaugoyeau, F. Viallet, S. Mesure, J. Massion, Coordination of axial rotation and step execution: Deficits in Parkinson’s disease, Gait Posture. 18 (2003) 150–157. doi:10.1016/S09666362(03)00034-1.
[8]
M.L. Mille, R.A. Creath, M.G. Prettyman, M. Johnson Hilliard, K.M. Martinez, C.D. MacKinnon, et al., Posture and locomotion coupling: A target for rehabilitation interventions in persons with Parkinson’s disease, Parkinsons. Dis. 2012 (2012). doi:10.1155/2012/754186.
15 [9]
J. V. Jacobs, J.G. Nutt, P. Carlson-Kuhta, M. Stephens, F.B. Horak, Knee trembling during freezing of gait represents multiple anticipatory postural adjustments, Exp. Neurol. 215 (2009) 334–341. doi:10.1016/j.expneurol.2008.10.019.
[10]
J.-P. Taylor, E.N. Rowan, D. Lett, J.T. O’Brien, I.G. McKeith, D.J. Burn, Poor attentional function predicts cognitive decline in patients with non-demented Parkinson’s disease independent of motor phenotype., J. Neurol. Neurosurg. Psychiatry. 79 (2008) 1318–1323. doi:10.1136/jnnp.2008.147629.
[11]
G. Alves, J.P. Larsen, M. Emre, T. Wentzel-Larsen, D. Aarsland, Changes in motor subtype and risk for incident dementia in Parkinson’s disease, Mov. Disord. 21 (2006) 1123–1130. doi:10.1002/mds.20897.
[12]
D.J. Burn, E.N. Rowan, L.M. Allan, S. Molloy, J.T. O’Brien, I.G. McKeith, Motor subtype and cognitive decline in Parkinson’s disease, Parkinson's disease with dementia, and dementia with Lewy bodies., J. Neurol. Neurosurg. Psychiatry. 77 (2006) 585–589. doi:10.1136/jnnp.2005.081711.
[13]
G. Vervoort, A. Bengevoord, E. Nackaerts, E. Heremans, W. Vandenberghe, A. Nieuwboer, Distal motor deficit contributions to postural instability and gait disorder in Parkinson’s disease, Behav. Brain Res. 287 (2015) 1–7. doi:10.1016/j.bbr.2015.03.026.
[14]
J. Nantel, J.C. McDonald, S. Tan, H. Bronte-Stewart, Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson’s disease, Neuroscience. 221 (2012) 151–156. doi:10.1016/j.neuroscience.2012.07.007.
[15]
R.G. Cohen, A. Chao, J.G. Nutt, F.B. Horak, Freezing of gait is associated with a mismatch between motor imagery and motor execution in narrow doorways, not with failure to judge doorway passability, Neuropsychologia. 49 (2011) 3981–3988. doi:10.1016/j.neuropsychologia.2011.10.014.
[16]
Q.J. Almeida, C.A. Lebold, Freezing of gait in Parkinson’s disease: a perceptual cause for a motor
16 impairment?, J. Neurol. Neurosurg. Psychiatry. 81 (2010) 513–8. doi:10.1136/jnnp.2008.160580. [17]
D. Cowie, P. Limousin, A. Peters, B.L. Day, Insights into the neural control of locomotion from walking through doorways in Parkinson’s disease, Neuropsychologia. 48 (2010) 2750–2757. doi:10.1016/j.neuropsychologia.2010.05.022.
[18]
S.L. Naismith, J.M. Shine, S.J.G. Lewis, The specific contributions of set-shifting to freezing of gait in Parkinson’s disease, Mov. Disord. 25 (2010) 1000–1004. doi:10.1002/mds.23005.
[19]
P.J. Sparto, S.I. Fuhrman, M.S. Redfern, S. Perera, J.R. Jennings, J.M. Furman, Postural adjustment errors during lateral step initiation in older and younger adults, Exp. Brain Res. 232 (2014) 3977–3989. doi:10.1007/s00221-014-4081-z.
[20]
P.J. Sparto, S.I. Fuhrman, M.S. Redfern, S. Perera, J.R. Jennings, R.D. Nebes, et al., Postural adjustment errors reveal deficits in inhibition during lateral step initiation in older adults, J. Neurophysiol. 109 (2013) 415–428.
[21]
R.G. Cohen, A.K. Klein, M. Nomurab, M. Fleming, M. Mancini, N. Giladi, et al., Inhibition, Executive Function, and Freezing of Gait, J. Pakinsons Disord. 4 (2014) 111–122. doi:10.3233/JPD-130221.
[22]
A. Delval, C. Tard, L. Defebvre, Why we should study gait initiation in Parkinson’s disease, Neurophysiol. Clin. 44 (2014) 69–76. doi:10.1016/j.neucli.2013.10.127.
[23]
J.R. Nocera, R. Roemmich, J. Elrod, L.J.P. Altmann, C.J. Hass, Effects of cognitive task on gait initiation in Parkinson disease: evidence of motor prioritization?, J. Rehabil. Res. Dev. 50 (2013) 699–708. doi:http://dx.doi.org/10.1682/JRRD.2012.06.0114.
[24]
S. Vallabhajosula, T.A. Buckley, M.D. Tillman, C.J. Hass, Age and Parkinson’s disease related kinematic alterations during multi-directional gait initiation, Gait Posture. 37 (2013) 280–286. doi:10.1016/j.gaitpost.2012.07.018.
[25]
B.E. Maki, W.E. McIlroy, Control of rapid limb movements for balance recovery: Age-related changes and implications for fall prevention, Age Ageing. 35 (2006) 12–18.
17 doi:10.1093/ageing/afl078. [26]
R. Sciadas, C. Dalton, J. Nantel, Effort to reduce postural sway affects both cognitive and motor performances in individuals with Parkinson’s disease, Hum. Mov. Sci. (2016) 135–140.
[27]
J.D. Holmes, M.E. Jenkins, A.M. Johnson, S.G. Adams, S.J. Spaulding, Dual-task interference: the effects of verbal cognitive tasks on upright postural stability in Parkinson’s disease., Parkinsons. Dis. 2010 (2010) 696492. doi:10.4061/2010/696492.
[28]
K. Uemura, T. Oya, Y. Uchiyama, Effects of visual interference on initial motor program errors and execution times in the choice step reaction, Gait Posture. 38 (2013) 68–72. doi:10.1016/j.gaitpost.2012.10.016.
18
19
Table 1 Freezing of gait (FoG) questionnaire, Montreal Cognitive Assessment (MoCA) and Trail Making B-A in freezers and non-freezers
FoG questionnaire MoCA Trail making B-A (s) Trail making B-A (%)
Non-Freezers 1.0 ± 1.0 27.0 ± 1.7 29 ± 23 201 ± 69.1
† Significantly different, p <0.05
Freezers 9.7 ± 5.1† 25.3 ± 3.4 70.3 ± 54.2 286.3 ± 134.4
P values 0.000 0.071 0.026 0.066
20
Table 2 Center of pressure (CoP) displacement amplitude (mm) and CoP velocity (mm/s) in the medial-lateral (ML) and anterior-posterior directions for Controls and individuals with Parkinson’s disease (PD) during the Green Go and Green Stop trials. Green Go ML 2.85 ± 0.54
Controls Green Stop 2.76 ± 0.48
Non-Freezers Green Go Green Stop 1.46 ± 0.40 † 1.43 ± 0.30 †
Freezers Green Go Green Stop 1.76 ± 0.77 † 1.76 ± 0.47 †
Range CoP (mm) 2.35 ± 0.45
2.28 ± 0.35
1.88 ± 0.31
*† 2.21 ± 0.50
ML 1.60 ± 0.44
1.62 ± 0.98
0.86 ± 1.25
0.23 ± 0.17
AP
1.28 ± 0.57
1.02 ± 1.36
0.42 ± 0.31
Contact (s) 2.33 ± 0.17 * 2.49 ± 0.28 † Significantly different from Controls ‡ Significantly different from non-freezers * GS different from GG p <0.05
2.51 ± 0.23
2.61 ± 0.32
AP
1.97 ± 0.66
1.74 ± 0.34 ‡†
†
0.69 ± 0.79 †
0.26 ± 0.16 †
†
0.78 ± 0.84
0.33 ± 0.19 †
Speed (mm/s) 1.52 ± 0.78
2.74 ± 0.31 *† 3.81 ± 1.4
‡†
21
Table 3 Center of pressure (CoP) root mean square (RMS) displacement (mm) and CoP velocity (mm/s) for Controls, non-freezers and freezers.
ML
Controls Red GO Red STOP 7.55 ± 6.03 5.02 ± 2.70*
Non-Freezers Red GO Red STOP 5.24 ± 2.96 4.70 ± 2.17
Freezers Red GO Red STOP 6.64 ± 4.06 3.60 ± 1.33*
AP
11.37 ± 6.71
76.35 ± 2.34*
6.98 ± 2.51
6.99 ± 2.69
7.93 ± 3.28
6.03 ± 2.17*
ML 11.40 ± 8.42
69.47 ± 2.98*
6.23 ± 32.59
6.09 ± 2.86
7.10 ± 2.68
4.78 ± 1.81*
AP 16.82 ± 7.10 11.98 ± 3.09* † Significantly different from Controls * GS different from GG p <0.05
9.38 ± 3.37†
9.41 ±3.27†
10.24 ± 2.89†
7.54 ± 2.11*†
CoP (mm)
VCoP (mm/s)