Table 2.

Result of the VR studies in PD-FOG

Author, year	Aim/Hypothesis	Results	Was the aim achieved/ hypothesis confirmed?
Naismith and Lewis, 2010 [10]	To validate a VR paradigm modeling FOG without requiring the individual to walk	Inaugural study which designed the standard VR paradigm used to elicit FOG in PD participants. Worse performance on the VR paradigm correlated with higher scores on FOG-Q (p<0.05).	+
Shine et al., 2011 [11]	To determine the neural correlates of FOG	Case study using fMRI compatible VR which identified a distinct pattern of brain activation and deactivation underlying freezing behavior (p<0.001; corrected with a false detection rate of p<0.05).	+
Shine et al., 2013 [12]	To determine whether the VR measures for FOG can differentiate PD-FOG and PD-nFOG, and whether these measures correlate with FOG elicited during Timed Up-and-Go	VR induced more motor arrests in PD-FOG compared to PD-nFOG (p<0.01). The number and duration of FOG episodes during the VR paradigm positively correlated with clinically observed FOG duration during the Timed Up-and-Go (p<0.05).	+
Shine et al., 2013 [13]	To investigate whether increased cognitive load was associated with different activation patterns in PD-FOG and PD-nFOG	PD-FOG are unable to properly recruit specific cortical and subcortical regions within the Cognitive Control Network while performing simultaneous motor and cognitive functions (corrected with a false detection rate of p<0.05)	+
Shine et al., 2013 [14]	To determine neural correlates of FOG during “off”	FOG is associated with increased basal ganglia inhibitory output, leading to a decrease in thalamic and brainstem information processing (p<0.05 with family wise error correction for multiple comparisons).	+
Shine et al., 2013 [15]	To determine whether FOG during the VR task was associated with impaired functional connectivity between the networks likely to be involved in FOG	During FOG, PD-FOG demonstrated decreased functional connectivity between the basal ganglia and the Cognitive Control Network in each hemisphere (alpha controlled by astrict Bonferroni; p=0.01, α/5 comparisons for network activity and p=0.005, α/10 comparisons for network connectivity).	+
Matar et al., 2013 [16]	Greater conflict resolution and environmental stimuli requiring increased processing will be associated with delayed motor outflow in PD-FOG compared to PD-nFOG and HC.	PD-FOG had increased response latency when exposed to stimuli with higher levels of conflict resolution or when increased levels of visuospatial processing were required, compared to PD-nFOG and HC (p<0.05).	+
Gilat et al., 2013 [17]	VR task will reproduce the key features of gait variability in PD.	The characteristic features of gait disturbance observed in PD-FOG can also be demonstrated with a VR paradigm: stride-time variability was greater in PD-FOG vs PD-nFOG, and was partially ameliorated by dopaminergic therapy (p<0.05 one-tailed).	+
Matar et al., 2014 [18]	Footstep latency within the VR task will be increased during the “off” state compared to the “on” state in PD-FOG.	Motor delays when processing environmentally salient cues (wide and narrow doorways, and opening of a sliding door) improved with levodopa in PD-FOG but not PD-nFOG (p<0.05).	+
Gilat et al., 2015 [19]	To investigate the neural correlates of turning deficits in PD and PD-FOG	Activation of inferior frontal regions and deactivation of premotor and superior parietal cortices; increased functional connectivity between subcortical regions while turning in PD-FOG (p<0.05 with false detection rate correction in the network-based statistics software).	+
Georgiades et al., 2016 [20]	PD-FOG will experience footstep initiation and cessation deficits during the VR task compared to PD-nFOG and HC.	PD-FOG had more deficits in motor initiation and stopping performance, including stop failure, compared to PD-FOG and HC (p<0.05).	+
Ehgoetz Martens et al., 2018 [6]	During episodes of FOG, fMRI will demonstrate be abnormal functional connectivity within and between cortico-striatal circuits. Network correlates of FOG will be associated with individual differences in the cognitive, motor and limbic features of FOG	Functional connectivity during FOG is correlated with particular cognitive, motor and limbic features, which may indicate subyptes of PD-FOG. During FOG, there was an overall loss of synchrony between the cortex and the striatum, as well as a loss of segregation and specificity between examined cortico-striatal pathways (p<0.05, connectivity strength either stronger or weaker than the 97.5th (or 2.5th) percentile of the null distribution, Cohen’s d ≥0.08)	+

FOG: freezing of gait, PD-FOG: Parkinson’s disease patients with freezing of gait, PD-nFOG: Parkinson’s disease patients without freezing of gait, VR: virtual reality, HC: healthy controls, FOG-Q: Freezing of gait questionnaire, +: achieved/confirmed.