Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer's disease

Abstract

Spatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here with a group of older adults (n = 56, 58-80 (67.9±5.2) year old, 31 females, 18.7±3.6 years of education), we provide evidence supporting the notion that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD), and the impairment is detectable using a double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the double cue spatial IOR paradigm may be useful in detecting MCI and early AD.

Fig 1. The double-cue spatial IOR experiment paradigm.

Within each trial, there were three sequentially presented visual stimuli—two cues (solid red circle) and one target (solid green circle)—with a blank screen in between. The three stimuli were presented serially. The two cue stimuli could appear in any of the three locations (left, middle, right), whereas the target stimuli could only appear in one of the two locations (left or right, but not the middle). Subjects were instructed to respond to the target (solid green circle) by pressing one of two buttons in the right hand to indicate whether the target was presented at the left or right location. The two cues were presented 200msec each, with a 250msec break in between. The second cue was followed by another 250msec break before the onset of the target, which was presented for 850msec. The next trial started 750msec after the offset of the target stimulus. There were five conditions based on the relationship of the locations in which the three stimuli were presented, aaa, abb, aba, aab, and abc (see main text). One example of each condition is shown here (in this example the first cue always appears in the left circle, but in the actual experiment the first and the second cue could appear in any of the three locations).

Fig 2. The double-cue spatial IOR experiment data.

Mean normRT from 21 low risk controls, 20 high risk controls, eight MCI participants, and seven mild AD participants. Error bars represent standard deviation.

Fig 3. The effect sizes of difference in spatial IOR effects between low-/high-risk controls and MCI or AD participants.

The IOR effects were measured as the difference between each pair of experimental conditions in Fig 1. (A) Low risk controls versus MCI (lower triangle) and AD (upper triangle) participants. (B) High risk controls versus MCI (lower triangle) and AD (upper triangle) participants. “Large” effect sizes (>0.8) are highlighted with a solid red box, and “medium” effect sizes (0.5–0.8) are highlighted with a dashed red box.

Fig 4. The correlation between Logical Memory (LM) subtests retention rate and two spatial IOR effects.

(A) IOR effect was measured as the difference between condition abb and aab (normRT_abb—normRT_aab). (B) IOR effect was measured as the difference between condition abb and aba (normRT_abb—normRT_aba). Each marker represents one participant: o, APOE4 non-carriers with an AD family history; +, APOE4 carriers without an AD family history; x, APOE4 carries with an AD family history. Error bars represent standard deviation.