This study describes a novel BAS task that requires no specialized equipment. We demonstrate that the BAS is strongly correlated with oculographically measured AS performance, indicating that BAS can be related to the extensive literature on the AS task in neurologic and psychiatric disease, as well as mechanistic studies of the AS task in both humans and nonhuman primates. In a cohort of cognitively normal participants and patients with neurodegenerative disease, BAS performance correlated more strongly with measures of executive function than memory, language, or visuospatial skill (after controlling for disease severity and education), similar to previous reports of oculographically measured AS performance.12
In a multicenter study, BAS performance was associated with both neuropsychological and informant-based measures of executive function in normal adults and individuals with a variety of neurologic disorders. Together, our results suggest the BAS is a cost-effective tool that can be used to assess both executive motor function and disease severity in a variety of neurologic disorders.
We found that subjects with a variety of dementia diagnoses exhibited an impaired ability to inhibit reflexive PS responses on the BAS. The similarity between this finding and previous results using an infrared eye tracker,11–13,33
along with the strong correlation of performance on the BAS and our laboratory AS task, further underscores the validity of the task. Impaired AS performance is correlated with structural alterations to the right greater than left premotor regions of the frontal lobes in focal lesion patients,34
and normal aging.4,36
Our results suggest that the BAS may be sensitive to damage to these same brain regions and could be used as a screen for such damage at the bedside.
The same frontoparietal network necessary for AS performance has been previously implicated in executive control in normal aging,4
and neurodegenerative disease.12–13
The observed correlation between BAS performance and neuropsychological measures of executive function further supports our hypothesis that BAS relies on the integrity of the same network as other AS paradigms. Because the correlations were strongest between BAS performance and executive function tasks that require greater motor skill in the form of drawing lines (Modified Trails and Design Fluency), it is possible that the BAS is more sensitive to executive motor control tasks as opposed to executive function as a whole. More work will be needed to confirm this hypothesis.
In our multicenter cohort, we also found that BAS performance strongly correlated with several measures of executive function, behavior, social cognition, and an informant measure of executive function: the FrSBe, a reliable measure of damage to the frontal lobes32
that produces a total score as well as subscales for Apathy, Disinhibition, and Executive Dysfunction. Even after controlling for demographics and processing speed, BAS performance was correlated with all 4 informant FrSBe-based scores. The FrSBe is sensitive to frontal lobe function in a variety of neurologic disorders including focal lesions, AD, Parkinson disease, and ALS. Our results suggest that the BAS may be useful in efficiently quantifying frontal lobe dysfunction in individuals for whom no informant is available.
BAS performance was also correlated with disease severity, as measured by MMSE and CDR-SB, in the UCSF cohort. Unlike a previously described bedside AS task,14
we did not observe a correlation between BAS performance and a test of memory. This finding is likely explained by the more diverse population of neurodegenerative disease subjects in our study and the fact that we controlled for disease severity (CDR-SB) in our analyses. Had we limited our analysis to MCI and AD subjects and not corrected for CDR-SB, our results would have been similar to the previous study (data not shown). Interestingly, BAS performance was different in MCI and dementia. Patients with AD, frontotemporal lobar degeneration, and PSP made more BAS errors than patients with MCI. Since we are unaware of any previously published reports of AS performance measured in MCI, further studies will be necessary to interpret the significance of these findings.
Subjects performed better on the bedside version of the AS task than the laboratory version. Several factors may contribute to this finding, including rater errors and time delay between testing modalities. A likely contributor is the presence of ambient lighting and other visual stimuli in the BAS condition that might partially counteract the effects of the gap stimulus, which increases error rate as a result of an increase in express saccade generation in the absence of fixation stimuli.1
In this respect, our findings are similar to those reported for a previous BAS task.14
Of note, our BAS task includes auditory cues to improve raters' data acquisition, which might also influence task performance.38,39
A limitation of the study was that we did not measure the interrater or intrarater reliability of the BAS. This will be necessary in the future for the BAS to be used in multicenter studies such as clinical trials, although the AS task has been used to measure disease progression in HD15
and genetic risk in first-degree relatives of patients with schizophrenia in large, multicenter studies.40
Such reliability studies are currently under way.
Our findings indicate the BAS is a valid measure of executive motor control in aging and neurologic disease, offering practitioners a rapid, simple clinical tool to evaluate executive functioning and dementia severity in their patients.