Progressive Prefrontal Cortex Dysfunction in Parkinson's Disease With Probable REM Sleep Behavior Disorder: A 3-Year Longitudinal Study

This study aimed to explore the disrupted prefrontal cortex activity specific to patients with Parkinson's disease (PD) with rapid eye movement sleep behavior disorder (RBD) compared with those without and to further examine the associations between these alterations and neuropsychological measurements. Ninety-six patients with early PD underwent both structural and functional MRI, and also neuropsychological assessments in the Parkinson's Progression Markers Initiative (PPMI) database. Of these, 46 patients who completed 1- and 3-year fMRI follow-up examinations were categorized as PD with probable RBD (PD-pRBD+) and without (PD-pRBD−). The left dorsolateral prefrontal cortex (DLPFC) seed-to-voxel functional connectivity analysis was conducted to evaluate the progressive neural alterations specific to PD-pRBD+ compared with PD-pRBD− over time. Furthermore, relationships between these alterations and neuropsychological performance were examined. Compared with patients with PD-pRBD−, patients with PD-pRBD+ initially exhibited connectivity deficits between the left DLPFC and the medial frontopolar cortex. Moreover, these patients further exhibited disrupted DLPFC connectivity in the lateral frontopolar cortex at the 3-year follow-up evaluation. Correlation analysis revealed that connectivity between the left DLPFC and frontopolar cortex was positively related to executive function in PD-pRBD+ after adjusting for nuisance variables. Progressive prefrontal cortex dysfunction associated with RBD in early PD may provide an effective subtype-specific biomarker of neurodegenerative progression, which may shed light on the neuropathological mechanisms underlying the clinical heterogeneity of this disease.

Novelty and uncertainty interact to regulate the balance between exploration and exploitation in the human brain.

Recent evidence suggests that both novelty and uncertainty act as potent features guiding exploration. However, these variables are often conflated with each other experimentally, and an understanding of how these attributes interact to regulate the balance between exploration and exploitation has proved elusive. Using a novel task designed to decouple stimulus novelty and estimation uncertainty, we identify separable behavioral and neural mechanisms by which exploration is colored. We show that uncertainty was avoided except when the information gained through exploration could be reliably exploited in the future. In contrast, and contrary to existing theory, novel options grew increasingly attractive relative to familiar counterparts irrespective of the opportunity to leverage their consequences and despite the uncertainty inherent to novel options. These findings led us to develop a formal computational framework in which uncertainty directed choice adapts to the prospective utility of exploration, while novel stimuli persistently draw favor as a result of inflated reward expectations biasing an exploitative strategy. Crucially, novelty is proposed to actively modulate uncertainty processing, effectively blunting the influence of uncertainty in shaping the subjective utility ascribed to novel stimuli. Both behavioral data and fMRI activity sampled from the ventromedial prefrontal cortex, frontopolar cortex and ventral striatum validate this model, thereby establishing a computational account that can not only explain behavior but also shed light on the functional contribution of these key brain regions to the exploration/exploitation trade-off. Our results point to multiple strategies and neural substrates charged with balancing the explore/exploit dilemma, with each targeting distinct aspects of the decision problem to foster a manageable decomposition of an otherwise intractable task.

Modulation of neural activity in frontopolar cortex drives reward-based motor learning

The frontopolar cortex (FPC) contributes to tracking the reward of alternative choices during decision making, as well as their reliability. Whether this FPC function extends to reward gradients associated with continuous movements during motor learning remains unknown. We used anodal transcranial direct current stimulation (tDCS) over the right FPC to investigate its role in reward-based motor learning. Nineteen healthy human participants practiced novel sequences of finger movements on a digital piano with corresponding auditory feedback. Their aim was to use trialwise reward feedback to discover a hidden performance goal along a continuous dimension: timing. We additionally modulated the contralateral motor cortex (left M1) activity, and included a control sham stimulation. Right FPC-tDCS led to faster learning compared to lM1-tDCS and sham through regulation of motor variability. Bayesian computational modelling revealed that in all stimulation protocols, an increase in the trialwise expectation of reward was followed by greater exploitation, as shown previously. Yet, this association was weaker in lM1-tDCS suggesting a less efficient learning strategy. The effects of frontopolar stimulation were dissociated from those induced by lM1-tDCS and sham, as motor exploration was more sensitive to inferred changes in the reward tendency (volatility). The findings suggest that rFPC-tDCS increases the sensitivity of motor exploration to updates in reward volatility, accelerating reward-based motor learning.

Reconciling Psychological and Neuroscientific Accounts of Reduced Motivation in Aging

Motivation is a hallmark of healthy aging, but the motivation to engage in effortful behavior diminishes with increasing age. Most neurobiological accounts of altered motivation in older adults assume that these deficits are caused by a gradual decline in brain tissue, while some psychological theories posit a switch from gain orientation to loss avoidance in motivational goals. Here, we contribute to reconcile the psychological and neural perspectives by providing evidence that frontopolar cortex (FPC), a brain region involved in cost-benefit weighting, increasingly underpins effort avoidance rather than engagement with age. Using anodal transcranial direct current stimulation together with effort-reward trade-offs, we find that the FPC’s function in effort-based decisions remains focused on cost-benefit calculations but appears to switch from reward seeking to cost avoidance with increasing age. This is further evidenced by exploratory, independent analysis of structural brain changes, showing that the relationship between the density of frontopolar neural tissue and willingness to exert effort differs in young versus older adults. Our results inform aging-related models of decision making by providing preliminary evidence that, in addition to cortical thinning, changes in goal orientation need to be considered in order to understand alterations in decision making over the lifespan.

The beauty of language structure: a single-case fMRI study of palindrome creation

Humans seem to be inherently driven to engage in wordplay. An example is the creation of palindromes –words, sentences, or even paragraphs that read the same backward and forward. This type of activity can be framed as a curiosity-driven behavior, in which individuals sacrifice finite resources, such as their time, to seek information that serves no direct purpose and in the absence of external rewards. Here, we present a single-case fMRI study of an experienced palindrome creator, who was scanned while he was immersed in generating palindromic sentences with different levels of difficulty. Blocks of palindrome creation were alternated with periods of resting and with the performance of a simple working memory (WM) task that served as control conditions. Relative to resting, palindrome creation recruited frontal domain-specific language networks and fronto-parietal domain-general networks. The comparison with the WM task evidenced a partial overlap with the multiple-demand cortex (MDC), which participates in solving different cognitively challenging tasks that require attention and cognitive control. Further, the implication of the inferior temporal gyrus (BA 37), extending ventrally to occipito-temporal regions (including the visual word form area), suggested the use of visual imagery and word form visualization to achieve this challenging task. Notably, greater difficulty during palindrome creation (difficult minus easy blocks) differentially activated the right frontopolar cortex (BA 10), a region that was also linked to successful palindrome resolution. The latter is in line with exploratory behavior to seek out information, in this case, with the exploration of new but interdependent linguistic segments within a complex internal model (i.e., a palindromic structure). These brain substrates also bear resemblance with those sustaining hard logical reasoning, altogether interestingly pointing to a commonplace for curiosity in discovering new and complex relations.

Frontopolar theta oscillations link metacognition with prospective decision making

Prospective decision making considers the future consequences of actions and therefore requires agents to represent their present subjective preferences reliably across time. Here, we test the link of frontopolar theta oscillations to both metacognitive ability and prospective choice behavior. We target these oscillations with transcranial alternating current stimulation while participants make decisions between smaller-sooner and larger-later monetary rewards and rate their choice confidence after each decision. Stimulation designed to enhance frontopolar theta oscillations increases metacognitive accuracy in reports of subjective uncertainty in intertemporal decisions. Moreover, the stimulation also enhances the willingness of participants to restrict their future access to short-term gratification by strengthening the awareness of potential preference reversals. Our results suggest a mechanistic link between frontopolar theta oscillations and metacognitive knowledge about the stability of subjective value representations, providing a potential explanation for why frontopolar cortex also shields prospective decision making against future temptation.

Modulation of neural activity in frontopolar cortex drives reward-based motor learning

The frontopolar cortex (FPC) contributes to tracking the reward of alternative choices during decision making, as well as their reliability. Whether this FPC function extends to reward gradients associated with continuous movements during motor learning remains unknown. We used anodal transcranial direct current stimulation (tDCS) over the right FPC to investigate its role in reward-based motor learning. Nineteen healthy human participants completed a motor sequence learning task using trialwise reward feedback to discover a hidden goal along a continuous dimension: timing. As additional conditions, we modulated the contralateral motor cortex (left M1) activity, and included a control sham stimulation. Right FPC-tDCS led to faster learning compared to lM1-tDCS and sham through regulation of motor variability. Computational modelling revealed that in all stimulation protocols, an increase in the trialwise expectation of reward was followed by greater exploitation, as shown previously. Yet, this association was weaker in lM1-tDCS suggesting a less efficient learning strategy. The effects of frontopolar stimulation were dissociated from those induced by lM1-tDCS and sham, as motor exploration was more sensitive to inferred changes in the reward tendency (volatility). The findings suggest that rFPC-tDCS increases the sensitivity of motor exploration to updates in reward volatility, accelerating reward-based motor learning.