Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN).

BACKGROUND: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials. METHODS: We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system. RESULTS: Data from individuals with CLN3 disease (N = 21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6-26 years). CONCLUSIONS: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): An auditory evoked potential study of the duration-evoked mismatch negativity (MMN).

Background: We interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of "duration" processing, a critical cue in speech perception. Given decrements in speech and language skills associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials. Methods: We employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system. Results: Data from individuals with CLN3 disease (N=21; range 6-28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N=41; ages 6-26 years). Conclusions: Results reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

Paradoxical improvement of cognitive control in older adults under dual-task walking conditions is associated with more flexible reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study.

Combining walking with a demanding cognitive task is traditionally expected to elicit decrements in gait and/or cognitive task performance. However, it was recently shown that, in a cohort of young adults, most participants improved performance when walking was added to performance of a Go/NoGo response inhibition task. The present study aims to extend these previous findings to an older adult cohort, to investigate whether this improvement when dual-tasking is observed in healthy older adults. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the Go/NoGo task, during sitting or walking on a treadmill, in 34 young adults and 37 older adults. Increased response accuracy during walking, independent of age, was found to correlate with slower responses to stimuli (r = 0.44) and with walking-related EEG amplitude modulations over frontocentral regions (r = 0.47) during the sensory gating (N1) and conflict monitoring (N2) stages of inhibition, and over left-lateralized prefrontal regions (r = 0.47) during the stage of inhibitory control implementation (P3). These neural activity changes are related to the cognitive component of inhibition, and they were interpreted as signatures of behavioral improvement during walking. On the other hand, aging, independent of response accuracy during walking, was found to correlate with slower treadmill walking speeds (r = -0.68) and attenuation in walking-related EEG amplitude modulations over left-dominant frontal (r = -0.44) and parietooccipital regions (r = 0.48) during the N2 stage, and over centroparietal regions (r = 0.48) during the P3 stage. These neural activity changes are related to the motor component of inhibition, and they were interpreted as signatures of aging. Older adults whose response accuracy 'paradoxically' improved during walking manifested neural signatures of both behavioral improvement and aging, suggesting that their flexibility in reallocating neural resources while walking might be maintained for the cognitive but not for the motor inhibitory component. These distinct neural signatures of aging and behavior can potentially be used to identify 'super-agers', or individuals at risk for cognitive decline due to aging or neurodegenerative disease.