Driving Ability in Alzheimer Disease Spectrum: Neural Basis, Assessment, and Potential Use of Optic Flow Event-Related Potentials

Abstract

Driving requires multiple cognitive functions including visuospatial perception and recruits widespread brain networks. Recently, traffic accidents in dementia, particularly in Alzheimer disease spectrum (ADS), have increased and become an urgent social problem. Therefore, it is necessary to develop the objective and reliable biomarkers for driving ability in patients with ADS. Interestingly, even in the early stage of the disease, patients with ADS are characterized by the impairment of visuospatial function such as radial optic flow (OF) perception related to self-motion perception. For the last decade, we have studied the feasibility of event-related potentials (ERPs) in response to radial OF in ADS and proposed that OF-ERPs provided an additional information on the alteration of visuospatial perception in ADS (1, 2). Hence, we hypothesized that OF-ERPs can be a possible predictive biomarker of driving ability in ADS. In this review, the recent concept of neural substrates of driving in healthy humans are firstly outlined. Second, we mention the alterations of driving performance and its brain network in ADS. Third, the current status of assessment tools for driving ability is stated. Fourth, we describe ERP studies related to driving ability in ADS. Further, the neural basis of OF processing and OF-ERPs in healthy humans are mentioned. Finally, the application of OF-ERPs to ADS is described. The aim of this review was to introduce the potential use of OF-ERPs for assessment of driving ability in ADS.

Keywords: Alzheimer disease spectrum; Alzheimer's disease; driving ability; event-related potentials; mild cognitive impairment; radial optic flow perception.

Figure 1

Activated brain regions during driving in fMRI. Distributed brain networks including occipital, parietal, frontal, motor, and cerebellar regions are mainly activated while driving only task. fMRI, functional magnetic resonance imaging. [Modified from (4), licensed under Creative Commons].

Figure 2

Radial OF motion. (A) When we move through our environment, radial OF pattern is produced by forward self-movement. (B) Coherent radial OF motion stimuli used in our study. We can create radial OF motion stimuli easily using random dots. Dots radiate from the focus of expansion, which corresponds to the observer's direction of heading. OF, optic flow.

Figure 3

Parallel visual pathways in humans. There are two major parallel streams: ventral and dorsal pathways in humans. Detailed functions of the two streams are provided in the text (see section Neural Basis of OF Perception in Healthy Humans). A recent study has revealed the importance of interconnection between IPL and SPL for OF processing (40) so that we modified this figure considering this point. d-d pathway, dorso-dorsal pathway; v-d pathway, ventro-dorsal pathway; LGN, lateral geniculate nucleus; MT, middle temporal area; MST, medial superior temporal area; IPL, inferior parietal lobule, SPL, superior parietal lobule; IT, inferior temporal cortex. [Modified from (41), Copyright (2012) with permission from IOS press].

Figure 4

ERPs in response to coherent OF and HO motion stimuli and their scalp topography in healthy subjects. (A) It is evident that the N170 and P200 are distinct motion-related components. The N170 component was distributed over occipito-temporal areas regardless of the stimulus type, extending further to the parietal region in the OF condition only. (B) The P200 component in response to OF stimuli was distributed over the parieto-central region while that of HO was distributed over the central region. The color bar represents the amplitude value (red = positive, blue = negative). Please note that this figure was presented at 2009 International Symposium on Early Detection and Rehabilitation Technology of Dementia. December 11–12, 2009, Okayama, Japan. ERPs, event-related potentials; HO, horizontal motion.

Figure 5

eLORETA-based statistical nonparametric maps for a comparison between OF and HO in GFP peaks of N170 and P200. (A) The current density of N170 was significantly elevated over the occipito-temporal areas including V5/MT+ in both stimulus conditions. (B) The current density of the parietal P200 for OF was significantly elevated in the left IPL (BA 39/40). Conversely, there was a significant elevation of the current density of the central P200 for HO in the bilateral SPL (BA 7). In the figure at the bottom, red and blue mean OF and HO, respectively. Please note that this figure was presented at 2009 International Symposium on Early Detection and Rehabilitation Technology of Dementia. December 11–12, 2009, Okayama, Japan. eLORETA, exact low resolution brain electromagnetic tomography; GFP, global field power; RM, random motion.

Figure 6

ERPs in response to coherent OF and HO motion stimuli in the MCI, AD and healthy control groups. MCI patients exhibit more prolongation of P200 latency for OF than healthy elderly adults, but no prolongation of N170 latency for both stimuli. AD patients show a prolongation of both N170 and P200 latencies compared with other groups. MCI, mild cognitive impairment. [Modified from (64), Copyright (2012) with permission from IEEE].

Figure 7

Correlation and ROC analyses. (A) Correlation of ERPs with delayed LM WMS-R scores. ERPs for OF motion stimuli are significantly correlated with delayed LM WMS-R scores. (B) The results of ROC curve analysis for discriminability of ERP components. The N170 and P200 latencies for OF motion have AUCs ≥ the threshold of 0.7 for acceptable discrimination. Please note that AD group was not recruited in this study [Modified from (1), Copyright (2016) with permission from IOS press]. LM WMS-R, logical memory in Wechsler Memory Scale-Revised; ROC, receiver operating characteristic; AUC, area under the curve.