Effects of external and internal cues on gait function in Williams syndrome Darren R. Hocking a,b, ⁎, Jennifer L. McGinley c , Simon A. Moss d , John L. Bradshaw a,e , Nicole J. Rinehart a a Centre for Developmental Psychiatry and Psychology, School of Psychology and Psychiatry, Monash University, Notting Hill, VIC, Australia b Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia c Centre for Clinical Research Excellence in Gait Analysis and Gait Rehabilitation, Murdoch Childrens Research Institute, Parkville, VIC, Australia d School of Psychology and Psychiatry, Monash University, Caulfield, VIC, Australia e Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, VIC, Australia abstract article info Article history: Received 30 September 2009 Received in revised form 26 November 2009 Accepted 22 December 2009 Available online 6 February 2010 Keywords: Gait Parkinsonian Williams syndrome Fronto-parietal Neurological Basal ganglia Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, is characterized by gait abnormalities that resemble basal ganglia-parkinsonian deficits in the internal regulation of stride length. In the current study, we explored whether visual or attentional cues would improve gait function in adults with WS, when compared to adults with Down syndrome (DS) and neurologically normal controls. The spatiotemporal characteristics of gait were measured using the GAITRite walkway while participants walked with visual cues set at 20% greater than preferred stride length (externally cued), or with an attentional strategy of maintaining the stride length without the assistance of visual cues (internally cued). Although the WS and DS groups were able to achieve the criterion and normalize stride length in both conditions, the WS group significantly reduced their gait speed and cadence in the externally cued condition when compared to controls. In the internally cued condition, the WS group also showed reduced speed and increased intra-individual variability in speed and stride time. These findings suggest that the primary deficit is not one of difficulty regulating stride length in WS, but rather indicates more widespread dysfunction within visuomotor regions. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Williams syndrome (WS) is a rare genetically based disorder, affecting 1 in 20,000 births, with more recent estimates of 1 in 7500 [1], caused by a microdeletion on a section of chromosome 7 including approximately 28 genes. The unique cognitive profile of WS has been well documented; this profile includes mild-to-moderate intellectual disability, with relative strengths in the verbal domain and face recognition, but with poor abilities in the visuospatial domain [2]. These characteristics are assumed to be related to specific dysfunction in the dorsal visual pathway in individuals with WS, an area which underpins the processing of spatial information associated with visually-guided movement; in contrast, ventral visual areas, which subserve perceptual processes such as object and face recognition, seem to be preserved [3]. Although several studies have shown visuomotor deficits within both upper limb and gait function in individuals with WS [4–7], the neural basis of the visuomotor abnormalities observed in WS are, as yet, unclear. Anecdotal and clinical observations indicate that visuomotor deficits in WS are more pronounced during more complex motor tasks, such as descending stairs or walking across uneven surfaces [5,8]. The results of our previous research on the spatiotemporal gait patterns associated with WS indicate that, when compared to a neurologically intact control group, individuals with WS are characterised by slow, wide-based (broad distance between the feet) and variable gait; however, we concluded that the primary deficit appears to be difficulty in regulating stride length rather than cadence (stepping frequency) [7]. More specifically, the WS group showed a consistently reduced stride length at any given increase in speed, with a disproportionate increase in cadence as speed increased. Accordingly, the gait disturbances observed in WS resembled basal ganglia-parkinsonian deficits in the internal regulation of stride length [9,10]. Imaging studies have shown that, when compared with healthy controls and individuals with Down syndrome (DS), the volume of the caudate nuclei and basal ganglia is significantly reduced in individuals with WS [11–14]. In contrast, individuals with DS show relatively preserved volume of the basal ganglia and posterior (parietal and occipital) regions, whereas frontal, temporal and cerebellar regions are typically reduced in size [15,16]. Imaging studies, however, have shown either preserved or increased volume of the cerebellum in WS [11,13,14,17,18]. Nevertheless, biochemical differences (reduction of the neurotransmitter N-acetylaspartate) in the cerebellum have been observed during performance on visuospatial and visuomotor tasks in WS [19]. One of the most consistent findings to date, in the imaging studies in WS, is primary dysfunction in the dorsal visual stream of the posterior parietal cortex [3,20,21]. However, it is not clear how these Journal of the Neurological Sciences 291 (2010) 57–63 ⁎ Corresponding author. Developmental Neuroscience and Genetic Disorders Laboratory, Monash University, School of Psychology and Psychiatry, Clayton Road, Clayton VIC 3800 Australia. Tel.: +61 3 9905 3966. E-mail address: darren.hocking@med.monash.edu.au (D.R. Hocking). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.12.026 Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns