Anatomically distinct areas within the basal ganglia encode flexible- and stable-value memories for visual objects (Hikosaka et al., 2014), but an important question remains: do they receive inputs from the same or different brain areas or neurons? To answer this question, we first located flexible and stable value-coding areas in the caudate head (CDh) and caudate tail (CDt) of two rhesus macaque monkeys, and then injected different retrograde tracers into these areas of each monkey. We found that CDh and CDt received different inputs from several cortical and subcortical areas including temporal cortex, prefrontal cortex, cingulate cortex, amygdala, claustrum and thalamus. Superior temporal cortex and inferior temporal cortex projected to both CDh and CDt, with more CDt-projecting than CDh-projecting neurons. In superior temporal cortex and dorsal inferior temporal cortex, layers 3 and 5 projected to CDh while layers 3 and 6 projected to CDt. Prefrontal and cingulate cortex projected mostly to CDh bilaterally, less to CDt unilaterally. A cluster of neurons in the basolateral amygdala projected to CDt. Rostral-dorsal claustrum projected to CDh while caudal-ventral claustrum projected to CDt. Within the thalamus, different nuclei projected to either CDh or CDt. The medial centromedian nucleus and lateral parafascicular nucleus projected to CDt while the medial parafascicular nucleus projected to CDh. The inferior pulvinar and lateral dorsal nuclei projected to CDt. The ventral anterior and medial dorsal nuclei projected to CDh. We found little evidence of neurons projecting to both CDh and CDt across the brain. These data suggest that CDh and CDt can control separate functions using anatomically separate circuits. Understanding the roles of these striatal projections will be important for understanding how value memories are created and stored.

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BackgroundAlzheimer’s and related dementias are on the rise, and older adults and their families are seeking accessible and effective ways to stave off or ameliorate mild cognitive impairment (MCI).AimThis pilot clinical trial (ClinicalTrials.gov Identifier: 03069391) examined neuropsychological and neurobiological outcomes of interactive physical and mental exercise.Participants and methodsOlder adults (MCI and caregivers) were enrolled in a 3-month, in-home trial of a portable neuro-exergame (the interactive Physical and Cognitive Exercise System [iPACES™]), in which they pedaled and steered along a virtual bike path to complete a list of errands (Memory Lane™). Neuropsychological function and salivary biomarkers were measured at pre-, mid-, and posttrial. Ten older adults complied with the recommended use of iPACES (complete dose; ≥2×/wk, 67% of the 15 who also had pre- and postevaluation data). Statistical analyses compared change over time and also change among those with a complete dose vs inadequate dose. Correlations between change in neuropsychological and biomarker measures were also examined.ResultsExecutive function and verbal memory increased after 3 months (p = 0.01; no significant change was found with an inadequate dose). Change in salivary biomarkers was moderately associated with increasing cognition (cortisol, r = 0.68; IGF-1, r = 0.37).ConclusionFurther research is needed, but these pilot data provide preliminary indications to suggest neuro-exergaming can impact cognitive function, perhaps via neurobiological mechanisms, and as such may provide an effective and practical way to promote healthy aging.

Given increasing longevity worldwide, older adults and caregivers are seeking ways to curb cognitive decline especially for those with mild cognitive impairment (MCI, now mild neurocognitive disorder, mNCD, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V). This quasi-experimental, within-subjects pilot clinical trial was designed to replicate and extend the study of cognitive benefits for MCI by improving upon our prior interactive Physical and Cognitive Exercise Study (iPACESTM v1.0) by increasing the usability of the neuro-exergame and exploring possible underlying neurobiological mechanisms. Older adults were enrolled in a three-month, in-home trial of a portable neuro-exergame (iPACES™ v2.0) where participants pedaled and steered along a virtual bike path (Memory Lane™). Neuropsychological function was assessed at baseline after component familiarization intervals (e.g., two weeks of exercise-only, game-only, etc.) and after three months of interactive neuro-exergame intervention. Fourteen participants were enrolled in the study and seven completed the final evaluation. Intent-to-treat analyses were conducted with imputed missing data (total n = 14). Significant improvement in executive function (Stroop) was found (d = 0.68, p = 0.02) only. Changes in salivary biomarkers (cortisol and insulin-like growth factor 1; IGF-1) were significantly associated with improved cognition. Further research is needed, but pilot data suggest that a portable in-home neuro-exergame may be an additional, practical tool to fight back against cognitive decline and dementia.