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Hippocampal and striatal circuits play important roles in spatial navigation. These regions integrate environmental information and receive intrinsic afferent inputs from the vestibular system. Past research indicates that galvanic vestibular stimulation (GVS) is a non-invasive technique that modulates hippocampal and striatal activities. There are also evidences for enhanced motor and cognitive functions through GVS. This study extends previous research to investigate whether noisy GVS may improve hippocampal- and striatal-associated aspects of spatial navigation performance. Using a virtual navigation task, we examined effects of noisy GVS on spatial learning and memory. To probe the participants’ sensitivity to hippocampal- or striatal-associated spatial information, we either enlarged the virtual environment’s boundary or replaced an intra-environmental location cue, respectively. Noisy GVS or sham stimulation was applied online during the learning phase in a within-subject crossover design. The results showed that noisy GVS enhanced spatial learning and the sensitivity foremost to hippocampal-dependent spatial information both in males and females. Individual differences in spatial working memory capacity moderated the effects of GVS, with individuals with lower capacity benefitting more from the stimulation. Furthermore, sex-related differences in GVS effects on the two forms of spatial representations may reflect differences between males and females in preferred spatial strategies.

Perceptual decisions entail the accumulation of evidence until a decision criterion is reached. The amount of noise in this process is inversely related to the behavioral performance of the decision-maker. Hence, reducing the amount of perceived noise could improve performance in perceptual decisions. In this study, we investigated whether providing monetary reward for correct responses in a perceptual decision-making task would enhance performance based on prior research linking noise reduction to the administration of reward. To this end, thirty-one healthy young adults carried out an incentivized dot tracking task (iDT) during recording of functional magnetic resonance imaging (fMRI). Behavioral responses were fitted to a Bayesian version of the drift-diffusion model that, among other parameters, also includes an estimate of sensory noise. Fifty percent of the trials were incentivized to compare rewarded with unrewarded trials regarding behavior, brain responses and estimates of model parameters. In order to establish a link between the noise parameter and fMRI activity, we correlated percent signal change (PSC) values from nucleus accumbens and caudate nucleus with noise levels in rewarded and unrewarded trials respectively. Although reward did not affect behavioral performance and model parameters, the fMRI analyses showed notable differences in nucleus accumbens, caudate nucleus and rostral anterior cingulate cortex in rewarded relative to unrewarded trials. Furthermore, higher PSC within nucleus accumbens was significantly associated with lower sensory noise levels, which was specific to rewarded trials. This work is consistent with previous findings on reward modulation of brain responses and marks a first step towards elucidating the effects of reward-induced noise suppression during perceptual decision-making.

Aging attenuates frontostriatal network functioning, which could lead to deficits in value computation when decision-making involves uncertainty. Although it has been shown that visually enhancing information saliency of outcome probability can improve decision-making in old age, mechanisms of this effect are still unclear. In the present study, the saliency of outcome probability was increased using a color-coding scheme as a decision aid in a mixed lottery choice task, and spontaneous eye-blink rate and pupillary responses were assessed in younger and older adults. Older adults showed lower value sensitivity than younger adults; however, increasing information saliency benefitted choice behaviors in both age groups. Furthermore, the decision aid reduced pupil size during decision-making in both age groups, suggesting that enhancing information saliency decreases cognitive demands of value computation. Baseline value sensitivity was negatively correlated with benefit of enhancing information saliency only in older adults. As value representations in older decision makers are less distinctive at baseline, they may have required more environmental compensation than younger adults.

Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

Quantitative electroencephalography (EEG) provides useful information about neurophysiological health of the aging brain. Current studies investigating EEG coherence and power for specific brain areas and frequency bands have yielded inconsistent results. This study assessed EEG coherence and power indices at rest measured over the whole skull and for a wide frequency range as global EEG markers for cognition in a sample at risk for dementia. Since global markers are more reliable and less error���prone than region��� and frequency���specific indices they might help to overcome previous inconsistencies. Global EEG coherence (1���30 Hz) and an EEG slowing score were assessed. The EEG slowing score was calculated by low���frequency power (1���8 Hz) divided by high���frequency power (9���30 Hz). In addition, the prognostic value of the two EEG indices for cognition and cognitive decline was assessed in a 5���year follow���up pilot study. Baseline global coherence correlated positively with cognition at baseline, but not with cognitive decline or with cognition at the 5���year follow���up. The EEG slowing ratio showed no significant association, neither with cognition at baseline or follow���up, nor with cognitive decline over a period of 5 years. The results indicate that the resting state global EEG coherence might be a useful and easy to assess electrophysiological correlate for neurocognitive health in older adults at risk for dementia. Because of the small statistical power for the follow���up analyses, the prognostic value of global coherence could not be determined in the present study. Future studies should assess its prognostic value with larger sample sizes., The study introduces global coherence across all regions and a wide range of frequency bands as a robust electrophysiological marker for cognition in older adults with a higher risk for developing dementia. In addition, it presents longitudinal electrophysiological data for coherence���cognition relationships. The study results suggest that global EEG coherence may be currently of higher benefit in research and in clinical application than region��� and frequency���specific coherence measures., publishedVersion

Adaptive behavior in daily life often requires the ability to acquire and represent sequential contingencies between actions and the associated outcomes. Although accumulating evidence implicates the role of dorsolateral prefrontal cortex (dlPFC) in complex value-based learning and decision-making, direct evidence for involvements of this region in integrating information across sequential decision states is still scarce. Using a 3-stage deterministic Markov decision task, here we applied offline, inhibitory low-frequency 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the left dlPFC in young male adults (n = 31, mean age = 23.8 years, SD = 2.5 years) in a within-subject cross-over design to study the roles of this region in influencing value-based sequential decision-making. In two separate sessions, each participant received 1-Hz rTMS stimulation either over the left dlPFC or over the vertex. The results showed that transiently inhibiting the left dlPFC impaired choice accuracy, particularly in situations in which the acquisition of sequential transitions between decision states and temporally lagged action-outcome contingencies played a greater role. Estimating parameters of a diffusion model from behavioral choices, we found that the diffusion drift rate, which reflects the efficiency of information integration, was attenuated by the stimulation. Moreover, the effects of rTMS interacted with session: individuals who could not efficiently integrate information across sequential states in the first session due to disrupted dlPFC function also could not catch up in performance during the second session with those individuals who could learn sequential transitions with intact dlPFC function in the first session. Taken together, our findings suggest that the left dlPFC is crucially involved in the acquisition of complex sequential relations and in the potential of such learning.

The error-related negativity (ERN/Ne) as well as the early and late error positivity (Pe) are electrophysiological correlates known to reflect error detection and error awareness. Despite much evidence on age differences in mastering response conflicts, the development and the functional distinctiveness of these components across the lifespan is still unclear. Here we investigated maturation- and aging-related differences in the ERN/Ne, the early and late Pe during a response conflict task in a lifespan sample that included 45 children, 42 adolescents, 39 younger and 34 older adults. Lifespan age differences were characterized by marked declines of all three components in older age, whereas clear maturation effects from childhood to adolescence were only observed for error detection reflected in the ERN/Ne component. Furthermore, using regression analyses, we examined functional relationships of the error monitoring components to behavioral indicators of task performance. Across all age groups, both the ERN/Ne and the early Pe were related to response accuracy, but only the early Pe was further associated with performance in a covariate task indicative of perceptual processing and attention capacities. Our results suggest that the ERN/Ne, the early and late Pe reflect distinct but complementary processes of error monitoring across the lifespan., Highlights • ERP correlates of error monitoring were investigated from childhood to old age. • Aging affected ERP components of error detection and awareness. • Maturation from childhood to adolescence only affected error detection (ERN/Ne). • Only the early Pe was related to perceptual processing and attention allocation. • ERN/Ne and Pe components distinct but complementary processes of error monitoring.

The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100���250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ��� 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer���s dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a novel difference score (��MMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ��MMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (�� = 0.38, p = 0.003; �� = ���0.27, p = 0.047, respectively). ��MMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (�� = 0.57, p = 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ��MMN as a potential biomarker for memory impairment in older adults at risk of dementia., publishedVersion

Depression is considered a potential risk factor for developing cognitive deficits and dementia during the progression of Parkinson’s disease (PD). Depression and dysthymia are also among the most frequent neuropsychiatric comorbidities, especially in later stages of PD. Regardless of the depression diagnosis, clinical and subsyndromal depressive symptoms in PD patients are associated with decreased daily functioning. However, very little is known about subsyndromal depressive symptoms and their relations to cognitive function and dopamine medication in PD. Here we investigated depressive symptoms and spatial memory performance in 34 early PD patients compared to 36 matched healthy controls in a pharmacobehavioral cross-over study.

Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer's disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n = 13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n = 14), or a control group (n = 20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer's disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (β ≥ 0.40, p ≤ 0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were related to FA scores at baseline (cognitive training skills and FA composite score, rs = 0.68, p = 0.05; functional physical fitness and fornix FA, r = 0.35, p = 0.03). Overall, we found no evidence of a link between short-term physical or cognitive activities and WMI changes, despite activity-related cognitive changes in older adults at risk of dementia. However, we found positive associations between the two targeted training outcomes and WMI, hinting at a potential of long-term activities to affect WMI. published

Korperliche Fitness wirkt positiv sowohl auf die kognitive Leistungsfahigkeit von gesunden alteren Erwachsenen als auch auf die von alteren Personen mit leichter kognitiver Beeintrachtigung und Demenz. Auch bei starkerer korperlicher Beeintrachtigung und Betreuungsbedurftigkeit kann sich ein multimodales korperliches Training im Sitzen noch begunstigend auf den Gesundheitszustand der Patienten auswirken. Grundlagenforschung im Tiermodell sowie erste Humanstudien weisen darauf hin, dass (aerobes) korperliches Training neuroplastische Prozesse (z. B. die Ausschuttung von Nervenwachstumsfaktoren) im Gehirn fordert und somit auch im hohen Alter noch kognitive Verbesserung ermoglicht.

Striatal dopamine depletion is a key pathophysiological feature of Parkinson's disease (PD) causing motor and nonmotor symptoms. Research on nonmotor symptoms has mainly focused on frontostriatal functions. However, dopamine pathways ascending from the ventral tegmental area also innervate hippocampal structures and modulate hippocampal-dependent functions, such as spatial memory. Using a virtual spatial navigation task, we investigated dopaminergic modulation of spatial memory in PD patients in a crossover medication ON/OFF design. We examined medication effects on striatal- and hippocampal-dependent spatial memory by either replacing a location cue in the environment or enlarging its spatial boundary. Key results indicate that in contrast to prior evidence for younger adults, PD patients, like their age-matched controls, rely more on striatal cue-based than hippocampal spatial learning. Medication facilitated striatal-dependent cue-location learning, whereas medication benefit in hippocampal boundary-related spatial memory depended on prior experience with the task. Medication effects on spatial memory were comparable to and independent of benefits on motor symptoms. These findings shed new light on dopaminergic modulation of hippocampal-striatal functions in PD.

Performance monitoring tasks are suitable for investigating aging-related decline in executive functions. However, little is known about performance monitoring in premature pathological aging and mild cognitive impairment (MCI). This study recorded the error-related negativity (ERN) and the correct-related negativity (CRN) as indices of performance monitoring andcompared these responses in older adults with MCI to the ones of younger and older adult controls. No differences in either ERN or CRN were found between younger and older adult controls. Compared to both control groups, we observed a more negatively pronouncedCRNin MCI subjects. Only in this group did the amplitude of theCRNnot differ from the one of the ERN. In general, larger differences between both components (i.e., ERN > CRN) were associated with better performances in cognitive tests requiring inhibition and executive control. These results indicate that electrophysiological correlates of performance monitoring (ERN and CRN) are differentially affected by aging and MCI.

Physical exercise has positive effects on cognitive functioning in both healthy older adults and ambulatory older adults with dementia. The present study investigated whether a 10-week multimodal movement intervention conducted in the seated position can slow cognitive deterioration in demented and physically very frail nursing-home residents. Our analysis revealed that training participants showed no further overall cognitive deterioration throughout the study and a significant improvement in the ADAS-Cog orientation/praxis subscore (p = .04). In contrast, the control group demonstrated a significant decline in the ADAS-Cog sum score (p = .02). These results might be of relevance for geriatric practice since they indicate that a short-term physical intervention – even in the seated position – can decelerate cognitive decline and dementia despite physical frailty.

The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18–89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2–4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.

The Editor listed in the published manuscript is incorrect. The correct Editor is Dr. Heidar-Ali Tajmir-Riahi. His affiliation is the University of Quebec at Trois-Rivieres, Canada.