Contextual novelty changes reward representations in the striatum

Reward representation in ventral striatum is boosted by perceptual novelty, although the mechanism of this effect remains elusive. Animal studies indicate a functional loop (Lisman and Grace, 2005) that includes hippocampus, ventral striatum, and midbrain as being important in regulating salience attribution within the context of novel stimuli. According to this model, reward responses in ventral striatum or midbrain should be enhanced in the context of novelty even if reward and novelty constitute unrelated, independent events. Using fMRI, we show that trials with reward-predictive cues and subsequent outcomes elicit higher responses in the striatum if preceded by an unrelated novel picture, indicating that reward representation is enhanced in the context of novelty. Notably, this effect was observed solely when reward occurrence, and hence reward-related salience, was low. These findings support a view that contextual novelty enhances neural responses underlying reward representation in the striatum and concur with the effects of novelty processing as predicted by the model of Lisman and Grace (2005)

Basal forebrain integrity and cognitive memory profile in healthy aging

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuro psychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. (C) 2009 Elsevier B.V. All rights reserved

Parcellation of the human substantia nigra based on anatomical connectivity to the striatum

Substantia nigra/ventral tegmental area (SN/VTA) subregions, defined by dopaminergic projections to the striatum, are differentially affected by health (e.g. normal aging) and disease (e.g. Parkinson's disease). This may have an impact on reward processing which relies on dopaminergic regions and circuits. We acquired diffusion tensor imaging (DTI) with probabilistic tractography in 30 healthy older adults to determine whether subregions of the SN/VTA could be delineated based on anatomical connectivity to the striatum. We found that a dorsomedial region of the SN/VTA preferentially connected to the ventral striatum whereas a more ventrolateral region connected to the dorsal striatum. These SN/VTA subregions could be characterised by differences in quantitative structural imaging parameters, suggesting different underlying tissue properties. We also observed that these connectivity patterns differentially mapped onto reward dependence personality trait. We show that tractography can be used to parcellate the SN/VTA into anatomically plausible and behaviourally meaningful compartments, an approach that may help future studies to provide a more fine-grained synopsis of pathological changes in the dopaminergic midbrain and their functional impact

Contextual novelty modulates the neural dynamics of reward anticipation

We investigated how rapidly the reward-predicting properties of visual cues are signaled in the human brain and the extent these reward prediction signals are contextually modifiable. In a magnetoencephalography study, we presented participants with fractal visual cues that predicted monetary rewards with different probabilities. These cues were presented in the temporal context of a preceding novel or familiar image of a natural scene. Starting at similar to 100 ms after cue onset, reward probability was signaled in the event-related fields (ERFs) over temporo-occipital sensors and in the power of theta (5-8 Hz) and beta (20-30 Hz) band oscillations over frontal sensors. While theta decreased with reward probability beta power showed the opposite effect. Thus, in humans anticipatory reward responses are generated rapidly, within 100 ms after the onset of reward-predicting cues, which is similar to the timing established in non-human primates. Contextual novelty enhanced the reward anticipation responses in both ERFs and in beta oscillations starting at similar to 100 ms after cue onset. This very early context effect is compatible with a physiological model that invokes the mediation of a hippocampal-VTA loop according to which novelty modulates neural response properties within the reward circuitry. We conclude that the neural processing of cues that predict future rewards is temporally highly efficient and contextually modifiable

Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection

Reliability and Reproducibility of Hadamard Encoded Pseudo-Continuous Arterial Spin Labeling in Healthy Elderly

The perfusion parameters cerebral blood flow (CBF) and arterial transit time (ATT) measured with arterial spin labeling (ASL) magnetic resonance imaging (MRI) provide valuable essentials to assess the integrity of cerebral tissue. Brain perfusion changes, due to aging, an intervention, or neurodegenerative diseases for example, could be investigated in longitudinal ASL studies with reliable ASL sequences. Generally, pseudo-continuous ASL (pCASL) is preferred because of its larger signal-to-noise ratio (SNR) compared to pulsed ASL (PASL) techniques. Available pCASL versions differ regarding their feature details. To date only little is known about the reliability and reproducibility of CBF and ATT measures obtained with the innovative Hadamard encoded pCASL variant, especially if applied on participants in old age. Therefore, we investigated an in-house developed Hadamard encoded pCASL sequence on a group of healthy elderly at two different 3 Tesla Siemens MRI systems (Skyra and mMR Biograph) and evaluated CBF and ATT reliability and reproducibility for several regions-of-interests (ROI). Calculated within-subject coefficients of variation (wsCV) demonstrated an excellent reliability of perfusion measures, whereas ATT appeared to be even more reliable than CBF [e.g., wsCV(CBF) = 2.9% vs. wsCV(ATT) = 2.3% for a gray matter (GM) ROI on Skyra system]. Additionally, a substantial agreement of perfusion values acquired on both MRI systems with an inter-session interval of 78 ± 17.6 days was shown by high corresponding intra-class correlation (ICC) coefficients [e.g., ICC(CBF) = 0.704 and ICC(ATT) = 0.754 for a GM ROI]. The usability of this novel Hadamard encoded pCASL sequence might improve future follow-up perfusion studies of the aging and/or diseased brain

Studying Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis with 7-T magnetic resonance

Ultra-high-field (UHF) magnetic resonance (MR) scanners, that is, equipment operating at static magnetic field of 7 tesla (7 T) and above, enable the acquisition of data with greatly improved signal-to-noise ratio with respect to conventional MR systems (e.g., scanners operating at 1.5 T and 3 T). The change in tissue relaxation times at UHF offers the opportunity to improve tissue contrast and depict features that were previously inaccessible. These potential advantages come, however, at a cost: in the majority of UHF-MR clinical protocols, potential drawbacks may include signal inhomogeneity, geometrical distortions, artifacts introduced by patient respiration, cardiac cycle, and motion. This article reviews the 7 T MR literature reporting the recent studies on the most widespread neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Structural integrity of the substantia nigra and subthalamic nucleus predicts flexibility of instrumental learning in older-age individuals

Flexible instrumental learning is required to harness the appropriate behaviors to obtain rewards and to avoid punishments. The precise contribution of dopaminergic midbrain regions (substantia nigra/ventral tegmental area [SN/VTA]) to this form of behavioral adaptation remains unclear. Normal aging is associated with a variable loss of dopamine neurons in the SN/VTA. We therefore tested the relationship between flexible instrumental learning and midbrain structural integrity. We compared task performance on a probabilistic monetary go/no-go task, involving trial and error learning of: "go to win," "no-go to win," "go to avoid losing," and "no-go to avoid losing" in 42 healthy older adults to previous behavioral data from 47 younger adults. Quantitative structural magnetization transfer images were obtained to index regional structural integrity. On average, both some younger and some older participants demonstrated a behavioral asymmetry whereby they were better at learning to act for reward ("go to win" > "no-go to win"), but better at learning not to act to avoid punishment ("no-go to avoid losing" > "go to avoid losing"). Older, but not younger, participants with greater structural integrity of the SN/VTA and the adjacent subthalamic nucleus could overcome this asymmetry. We show that interindividual variability among healthy older adults of the structural integrity within the SN/VTA and subthalamic nucleus relates to effective acquisition of competing instrumental responses

Heart Rate Variability During Physical Exercise Is Associated With Improved Cognitive Performance in Alzheimer's Dementia Patients-A Longitudinal Feasibility Study

Heart rate variability (HRV) rapidly gains attention as an important marker of cardiovascular autonomic modulation. Moreover, there is evidence for a link between the autonomic deficit measurable by reduced HRV and the hypoactivity of the cholinergic system, which is prominently affected in Alzheimer's disease (AD). Despite the positive influence of physical exercise on cognition and its promising association with HRV, previous studies did not explore the effect of long-term physical exercise in older adults with AD. Taking advantage of a longitudinal study we analyzed the effect of a 20-week dual task training regime (3 × 15-min per week) on the vagal mediated HRV index RMSSD (root mean square of successive RR interval differences) during physical exercise and the short-term memory performance in a AD cohort (N = 14). Each training contained physical exercise on a bicycle ergometer while memorizing 30 successively presented pictures as well as the associated post-exercise picture recognition memory test. Linear-mixed modeling revealed that HRV-RMSSD significantly increased over the intervention time. Moreover, the reaction time in the picture recognition task decreased while the accuracy remained stable. Furthermore, a significantly negative relationship between increased fitness measured by HRV-RMSSD and decreased reaction time was observed. This feasibility study points to the positive effects of a dual task regime on physical and cognitive fitness in a sample with impaired cognitive performance. Beyond this, the results show that the responsiveness of parasympathetic system as measured with HRV can be improved in patients with dementia