Early Alzheimer's disease blocks responses to accelerating self-movement

Abstract

We assessed the cortical processing of self-movement stimuli in aging and Alzheimer's disease (AD). Our goal was to identify distinguishing effects on neural mechanisms related to driving and navigation. Young (YNC) and older (ONC) normal controls, and early AD patients (EAD) viewed real-world videos and dot motion stimuli simulating self-movement scenes. We recorded visual motion event related potentials (VMERPs) to stimulus motion coherence and speed. Aging delays motion evoked N200s, whereas AD diminishes response amplitudes. Early Alzheimer's disease patients respond to increments in motion coherence, but they are uniquely unresponsive to increments in motion speed that simulate accelerating self-movement. AD-related impairments of self-movement processing may have grave consequences for driving safety and navigational independence.

Figure 1

Real-world video stimulus paradigm and evoked responses. A. Coherence stimuli consisted of frames in which the image was divided into increasing numbers of equal sized, randomly repositioned, segments. A four-segment image is shown with the arrows representing the direction of local motion. B. Speed stimuli consisted of increasing speeds of simulated straight-ahead self-movement. C–D. Responses to naturalistic videos at each stimulus level (line colors) for each subject group (YNC, ONC, and EAD). C. All subject groups show clear responses at all coherence levels. D. Speed stimuli evoke clear N200s in YNCs and ONCs groups, with the fastest speeds generating the biggest amplitudes, whereas EADs show only marginal responses, regardless of stimulus speed. E–F. Line plots of mean N200 amplitudes (+/− SE) for each subject group (line color) in the coherence (E) and speed (F) stimulus paradigms. N200 response amplitudes differed across coherence, speed, and subject group. The most fragmented coherence (198–36 segments) evoked moderate responses in all groups, whereas stimuli with fewer fragments evoked a range of responses from low amplitudes (16–8 segments) to higher amplitudes (4–1 segment). The responses to speed stimuli increased in amplitude with increasing speed in all groups.

Figure 2

A–B. Animated motion sequences composed of white dots on a black background were used to simulate self-motion, while subjects maintained fixation on a red dot target placed in the center of the screen. A. Coherence trials began with zero coherence motion (fully random), followed by a series of patterned motion stimuli, and ended with vertical motion (not shown) to prompt a button press response. B. Speed trials began with zero coherence motion, followed by a series of speed stimuli, and terminated by 100% coherence vertical motion with randomly assigned upward or downward direction to prompt a button press (not shown). C–D. Group averages of optic flow responses to all stimuli of the specified motion coherence or dot speed (line color) that were immediately preceded by a 0% coherence stimulus; the black line is the grand average across all conditions in that study. Optic flow evoked large N200 responses in young subjects, somewhat smaller and delayed responses in older adults, and substantially smaller responses in AD patients for all coherence and speed conditions. C. N200 amplitudes increase and latencies decrease with higher motion coherence. D. Dot speed at onset of optic flow had no effect on N200 amplitude or latency.

Figure 3

Mean peak amplitudes and latencies of N200 responses evoked by radial motion onset at each coherence or speed for each subject group (line color). A–B. Higher coherence levels generate larger amplitude and shorter latency responses in all groups. YNC’s responses are faster at all coherence levels compared to both ONCs and EADs. C–D. Faster speeds at motion onset did not result in significant differences in either amplitude or latency for any group. N200 amplitude clearly separated the EAD from the ONC and YNC groups, and latency separated the old from the young.

Figure 4

Mean peak amplitudes and latencies of N200 responses evoked by coherence (A–B) and speed (C–D) increments for each subject group (line color). A–B. Higher coherence increments generate larger amplitude and shorter latency responses in all groups. C–D. EADs are insensitive to the magnitude of speed increments, while YNCs and ONCs show larger responses to bigger increments. N200 latencies separate YNCs from both ONCs and EADs.

Figure 5

A behavioral catch paradigm was used to measure of sustained attention in all trials. A. Catch stimuli were presented after 9 to 15 optic flow stimuli and consisted of either upward or downward vertically moving dots with 100% coherence. Subjects pressed the far button for upward motion and the near button for downward motion. B. Response accuracy was measured as the percentage of correct responses across all coherence and speed conditions. Several EADs showed poor task performance and were omitted from a higher accuracy EAD sub-group. YNC subjects showed the greatest accuracy, with decreasing performance from ONCs and EADs. C. Response times (ms) were calculated as the interval between catch stimulus onset and button press. YNC subjects showed the shortest times, with increasing times from ONCs and EADs. D. Averaged N200s from all groups and the higher accuracy EAD sub-group show that group differences are not attributable to attentional differences.