Right fronto-parietal networks mediate the neurocognitive benefits of enriched environments.

Exposure to enriched environments throughout a lifetime, providing so-called reserve, protects against cognitive decline in later years. It has been hypothesized that high levels of alertness necessitated by enriched environments might strengthen the right fronto-parietal networks to facilitate this neurocognitive resilience. We have previously shown that enriched environments offset age-related deficits in selective attention by preserving grey matter within right fronto-parietal regions. Here, using neurite orientation dispersion and density imaging, we examined the relationship between enriched environments, microstructural properties of fronto-parietal white matter association pathways (three branches of the superior longitudinal fasciculus), structural brain health (atrophy), and attention (alertness, orienting and executive control) in a group of older adults. We show that exposure to enriched environments is associated with a lower orientation dispersion index within the right superior longitudinal fasciculus 1 which in turn mediates the relationship between enriched environments and alertness, as well as grey and white matter atrophy. This suggests that enriched environments may induce white matter plasticity (and prevent age-related dispersion of axons) within the right fronto-parietal networks to facilitate the preservation of neurocognitive health in later years.

Right Lateralized Brain Reserve Offsets Age-Related Deficits in Ignoring Distraction.

Age-related deterioration of attention decreases the ability to stay focused on the task at hand due to less efficient selection of relevant information and increased distractibility in the face of irrelevant, but salient stimuli. While older (compared with younger) adults may have difficulty suppressing salient distractors, the extent of these challenges differs vastly across individuals. Cognitive reserve measured by proxies of cognitively enriching life experiences, such as education, occupation, and leisure activities, is thought to mitigate the effects of the aging process and account for variability in trajectories of cognitive decline. Based on combined behavioral and neuroimaging (voxel-based morphometry) analyses of demographic, cognitive, and neural markers of aging and cognitive reserve proxy measures, we examine here predictors of variability in the age-related changes in attention function, indexed by ability to suppress salient distraction. Our findings indicate that in healthy (neurotypical), aging gray matter volume within several right lateralized fronto-parietal brain regions varies according to both levels of cognitive reserve (education) and the capacity to effectively select visual stimuli amid salient distraction. Thus, we provide here novel experimental evidence supporting Robertson's theory of a right lateralized neural basis for cognitive reserve.

Evidence accumulation during perceptual decisions in humans varies as a function of dorsal frontoparietal organization.

Animal neurophysiological studies have identified neural signals within dorsal frontoparietal areas that trace a perceptual decision by accumulating sensory evidence over time and trigger action upon reaching a threshold. Although analogous accumulation-to-bound signals are identifiable on extracranial human electroencephalography, their cortical origins remain unknown. Here neural metrics of human evidence accumulation, predictive of the speed of perceptual reports, were isolated using electroencephalography and related to dorsal frontoparietal network (dFPN) connectivity using diffusion and resting-state functional magnetic resonance imaging. The build-up rate of evidence accumulation mediated the relationship between the white matter macrostructure of dFPN pathways and the efficiency of perceptual reports. This association between steeper build-up rates of evidence accumulation and the dFPN was recapitulated in the resting-state networks. Stronger connectivity between dFPN regions is thus associated with faster evidence accumulation and speeded perceptual decisions. Our findings identify an integrated network for perceptual decisions that may be targeted for neurorehabilitation in cognitive disorders.

Catecholamine Modulation of Evidence Accumulation during Perceptual Decision Formation: A Randomized Trial.

Recent behavioral modeling and pupillometry studies suggest that neuromodulatory arousal systems play a role in regulating decision formation but neurophysiological support for these observations is lacking. We employed a randomized, double-blinded, placebo-controlled, crossover design to probe the impact of pharmacological enhancement of catecholamine levels on perceptual decision-making. Catecholamine levels were manipulated using the clinically relevant drugs methylphenidate and atomoxetine, and their effects were compared with those of citalopram and placebo. Participants performed a classic EEG oddball paradigm that elicits the P3b, a centro-parietal potential that has been shown to trace evidence accumulation, under each of the four drug conditions. We found that methylphenidate and atomoxetine administration shortened RTs to the oddball targets. The neural basis of this behavioral effect was an earlier P3b peak latency, driven specifically by an increase in its buildup rate without any change in its time of onset or peak amplitude. This study provides neurophysiological evidence for the catecholaminergic enhancement of a discrete aspect of human decision-making, that is, evidence accumulation. Our results also support theoretical accounts suggesting that catecholamines may enhance cognition via increases in neural gain.

Dopamine restores cognitive motivation in Parkinson's disease.

Disorders of motivation, such as apathy, are common in Parkinson's disease, and a key feature of such disorders is a greater aversion to effort. In humans, the experience of cognitive effort is ubiquitous, and cognitive apathy has traditionally been considered distinct and separable from other subtypes. Surprisingly, however, the neurobiology of cognitive motivation is poorly understood. In particular, although dopamine has a well-characterized role in incentivizing physically effortful behaviour, a critical, unresolved issue is whether its facilitatory role generalizes to other domains. Here, we asked how dopamine modulates the willingness of patients with Parkinson's disease to invest cognitive effort in return for reward. We tested 20 patients with idiopathic Parkinson's disease across two counterbalanced sessions-ON and OFF their usual dopaminergic medication-and compared their performance to 20 healthy age-matched controls. We applied a novel task in which we manipulated cognitive effort as the number of rapid serial visual presentation streams to which participants had to attend. After training participants to ceiling performance, we then asked them to choose between a low-effort/low-reward baseline option, and a higher-effort/higher-reward offer. Computational models of choice behaviour revealed four key results. First, patients OFF medication were significantly less cognitively motivated than controls, as manifest by steeper cognitive effort discounting functions in the former group. Second, dopaminergic therapy improved this deficit, such that choices in patients ON medication were indistinguishable from controls. Third, differences in motivation were also accompanied by independent changes in the stochasticity of individuals' decisions, such that dopamine reduced the variability in choice behaviour. Finally, choices on our task correlated uniquely with the subscale of the Dimensional Apathy Scale that specifically indexes cognitive motivation, which suggests a close relationship between our laboratory measure of cognitive effort discounting and subjective reports of day-to-day cognitive apathy. Importantly, participants' choices were not confounded by temporal discounting, probability discounting, physical demand, or varying task performance. These results are the first to reveal the central role of dopamine in overcoming cognitive effort costs. They provide an insight into the computational mechanisms underlying cognitive apathy in Parkinson's disease, and demonstrate its amenability to dopaminergic therapy. More broadly, they offer important empirical support for prominent frameworks proposing a domain-general role for dopamine in value-based decision-making, and provide a critical link between dopamine and multidimensional theories of apathy.

Prefrontal Modulation of Visual Processing and Sustained Attention in Aging, a tDCS-EEG Coregistration Approach.

The ability to sustain attention is integral to healthy cognition in aging. The right PFC (rPFC) is critical for maintaining high levels of attentional focus. Whether plasticity of this region can be harnessed to support sustained attention in older adults is unknown. We used transcranial direct current stimulation to increase cortical excitability of the rPFC, while monitoring behavioral and electrophysiological markers of sustained attention in older adults with suboptimal sustained attention capacity. During rPFC transcranial direct current stimulation, fewer lapses of attention occurred and electroencephalography signals of frontal engagement and early visual attention were enhanced. To further verify these results, we repeated the experiment in an independent cohort of cognitively typical older adults using a different sustained attention paradigm. Again, prefrontal stimulation was associated with fewer attentional lapses. These experiments suggest the rPFC can be manipulated in later years to increase top-down modulation over early sensory processing and improve sustained attention performance. This holds valuable information for the development of neurorehabilitation protocols to ameliorate age-related deficits in this capacity.

Plasticity of the Right-Lateralized Cognitive Reserve Network in Ageing.

Cognitive reserve (CR) is the phenomenon where older adults with more cognitively stimulating environments show less age-related cognitive decline. The right-lateralized fronto-parietal network has been proposed to significantly contribute to CR and visual attention in ageing. In this study we tested whether plasticity of this network may be harnessed in ageing.We assessed CR and parameters of visual attention capacity in older adults. Transcranial direct current stimulation (tDCS) was employed to increase right fronto-parietal activity during a lateralized whole-report task. At baseline, older adults with greater CR showed a stronger hemifield asymmetry in processing speed towards the left visual-field, indicative of stronger involvement of the right hemisphere in these individuals. Correspondingly, processing speed improved during right prefrontal tDCS. Older adults with lower levels of CR showed tDCS-related improvements in processing speed in the left but not right hemifield: thus tDCS temporarily altered their processing speed asymmetry to resemble that of their high reserve peers.The finding that stronger right hemisphere involvement is related to CR supports Robertson's theory. Furthermore, preserved plasticity within the right prefrontal cortex in older adults suggests this is a viable target area to improve visual processing speed, a hallmark of age-related decline.