Erich S. Tusch

In vivo evidence for neuroplasticity in older adults

Neuroplasticity can be conceptualized as an intrinsic property of the brain that enables modification of function and structure in response to environmental demands. Neuroplastic strengthening of synapses is believed to serve as a critical mechanism underlying learning, memory, and other cognitive functions. Ex vivo work investigating neuroplasticity has been done on hippocampal slices using high frequency stimulation. However, in vivo neuroplasticity in humans has been difficult to demonstrate. Recently, a long-term potentiation-like phenomenon, a form of neuroplastic change, was identified in young adults by differences in visual evoked potentials (VEPs) that were measured before and after tetanic visual stimulation (TVS). The current study investigated whether neuroplastic changes in the visual pathway can persist in older adults. Seventeen healthy subjects, 65 years and older, were recruited from the community. Subjects had a mean age of 77.4 years, mean education of 17 years, mean MMSE of 29.1, and demonstrated normal performance on neuropsychological tests. 1Hz checkerboard stimulation, presented randomly to the right or left visual hemi-field, was followed by 2min of 9Hz stimulation (TVS) to one hemi-field. After 2min of rest, 1Hz stimulation was repeated. Temporospatial principal component analysis was used to identify the N1b component of the VEPs, at lateral occipital locations, in response to 1Hz stimulation pre- and post-TVS. Results showed that the amplitude of factors representing the early and late N1b component was substantially larger after tetanic stimulation. These findings indicate that high frequency visual stimulation can enhance the N1b in cognitively high functioning old adults, suggesting that neuroplastic changes in visual pathways can continue into late life. Future studies are needed to determine the extent to which this marker of neuroplasticity is sustained over a longer period of time, and is influenced by age, cognitive status, and neurodegenerative disease.

Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity

The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models.

Changes in Neural Activity Underlying Working Memory after Computerized Cognitive Training in Older Adults

Computerized cognitive training (CCT) may counter the impact of aging on cognition, but both the efficacy and neurocognitive mechanisms underlying CCT remain controversial. In this study, 35 older individuals were randomly assigned to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring five weeks of five ∼40 min sessions per week. Before and after the 5-week intervention, event-related potentials were measured while subjects completed a visual n-back task with three levels of demand (0-back, 1-back, 2-back). The anterior P3a served as an index of directing attention and the posterior P3b as an index of categorization/WM updating. We hypothesized that adaptive CCT would be associated with decreased P3 amplitude at low WM demand and increased P3 amplitude at high WM demand. The adaptive CCT group exhibited a training-related increase in the amplitude of the anterior P3a and posterior P3b in response to target stimuli across n-back tasks, while subjects in the active control CCT group demonstrated a post-training decrease in the anterior P3a. Performance did not differ between groups or sessions. Larger overall P3 amplitudes were strongly associated with better task performance. Increased post-CCT P3 amplitude correlated with improved task performance; this relationship was especially robust at high task load. Our findings suggest that adaptive WM training was associated with increased orienting of attention, as indexed by the P3a, and the enhancement of categorization/WM updating processes, as indexed by the P3b. Increased P3 amplitude was linked to improved performance; however. there was no direct association between adaptive training and improved performance.

Age-related differences in early novelty processing: using PCA to parse the overlapping anterior P2 and N2 components.

Previous work demonstrated age-associated increases in the anterior P2 and age-related decreases in the anterior N2 in response to novel stimuli. Principal component analysis (PCA) was used to determine if the inverse relationship between these components was due to their temporal and spatial overlap. PCA revealed an early anterior P2, sensitive to task relevance, and a late anterior P2, responsive to novelty, both exhibiting age-related amplitude increases. A PCA factor representing the anterior N2, sensitive to novelty, exhibited age-related amplitude decreases. The late P2 and N2 to novels inversely correlated. Larger late P2 amplitude to novels was associated with better behavioral performance. Age-related differences in the anterior P2 and N2 to novel stimuli likely represent age-associated changes in independent cognitive operations. Enhanced anterior P2 activity (indexing augmentation in motivational salience) may be a compensatory mechanism for diminished anterior N2 activity (indexing reduced ability of older adults to process ambiguous representations).

Increased Early Processing of Task-Irrelevant Auditory Stimuli in Older Adults

The inhibitory deficit hypothesis of cognitive aging posits that older adults’ inability to adequately suppress processing of irrelevant information is a major source of cognitive decline. Prior research has demonstrated that in response to task-irrelevant auditory stimuli there is an age-associated increase in the amplitude of the N1 wave, an ERP marker of early perceptual processing. Here, we tested predictions derived from the inhibitory deficit hypothesis that the age-related increase in N1 would be 1) observed under an auditory-ignore, but not auditory-attend condition, 2) attenuated in individuals with high executive capacity (EC), and 3) augmented by increasing cognitive load of the primary visual task. ERPs were measured in 114 well-matched young, middle-aged, young-old, and old-old adults, designated as having high or average EC based on neuropsychological testing. Under the auditory-ignore (visual-attend) task, participants ignored auditory stimuli and responded to rare target letters under low and high load. Under the auditory-attend task, participants ignored visual stimuli and responded to rare target tones. Results confirmed an age-associated increase in N1 amplitude to auditory stimuli under the auditory-ignore but not auditory-attend task. Contrary to predictions, EC did not modulate the N1 response. The load effect was the opposite of expectation: the N1 to task-irrelevant auditory events was smaller under high load. Finally, older adults did not simply fail to suppress the N1 to auditory stimuli in the task-irrelevant modality; they generated a larger response than to identical stimuli in the task-relevant modality. In summary, several of the study’s findings do not fit the inhibitory-deficit hypothesis of cognitive aging, which may need to be refined or supplemented by alternative accounts.

Task-Irrelevant Novel Sounds have Antithetical Effects on Visual Target Processing in Young and Old Adults

In young adults, primary visual task processing can be either enhanced or disrupted by novel auditory stimuli preceding target events, depending on task demands. Little is known about this phenomenon in older individuals, who, in general, are more susceptible to distraction. In the current study, age-related differences in the electrophysiological effects of task-irrelevant auditory stimuli on visual target processing were examined. Under both low and high primary task loads, the categorization/updating process in response to visual targets preceded by auditory novels, as indexed by the target P3 component, was enhanced in young, but diminished in old adults. In both age groups, the alerting/orienting response to novel auditory stimuli, as measured by the P3a, was smaller under high task load, whereas redirecting attention to the visual task after a novel auditory event, as indexed by the reorienting negativity (RON), tended to be augmented under high task load. Old subjects generated a smaller P3a and RON. We conclude that task irrelevant novel auditory stimuli have the opposite effect on the processing of visual targets in young and old adults. This finding may help explain age-related increases in the disruption of primary task activity by irrelevant, but salient auditory events.

THE FEASIBILITY OF A HOME-BASED, SUBJECT-CONTROLLED, INTERACTIVE PHYSICAL EXERCISE PROGRAM TO PROMOTE COGNITIVE HEALTH IN OLDER ADULTS

Background:Increased physical activity (PA) is associated with better cognitive function. We investigated whether individuals with memory problems and additional cerebrovascular risk factors (CVD) could increase PA in the short-term and maintain adherence to a PA program in the long-term. We also examined factors influencing PA adherence.Methods:The AIBLActive trial recruited participants with mild cognitive impairment (MCI) or subjective memory complaints (SMC) and at least 1 CVD risk factor from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). They were randomly assigned to a control or PA group. The control group continued their usual PA throughout the study. The PA group was given a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Scheduled group-specific phone calls (n1⁄418) and newsletters (n1⁄417) were administered to both groups over 24 months. The PA group recorded sessions in diaries and adherence was calculated from the number of sessions recorded expressed as the percentage of the sessions prescribed. At baseline, 6, 12 and 24 months participants completed fitness (6-minute walk distance); PA and PA self-efficacy (one’s confidence to be physically active) questionnaires; cognitive and health assessments. Results:The adherence results for the PA group (n1⁄455) comprising of 53% women are reported. At baseline 24% were defined as inactive; men were significantly older than women; 74.7(6SD 5.6) versus 70.1(4.8) years respectively. Five participants did not start the intervention. After 24 months 96% were still in the study. After 6 months mean PA adherence was 83.5% and declined over the trial with mean 24-month adherence being 75.2%. Age, gender andMCI did not significantly influence adherence. Higher baseline self-efficacy (p<0.05) was associated with higher adherence in the first 6months with higher baseline self-efficacy (p<0.05) and fitness (p<0.01) associated with higher 24-month adherence. Positive program enjoyment, helpfulness of the telephone calls and newsletters were reported by 94%; 98% and 93% of participants respectively. Conclusions:The high retention and adherence rates in both the short and long-term demonstrate that this PA program was both achievable and acceptable in this target group.