Neural correlates of Traditional Chinese Medicine induced advantageous risk-taking decision making

This fMRI study examined the neural correlates of the observed improvement in advantageous risk-taking behavior, as measured by the number of adjusted pumps in the Balloon Analogue Risk Task (BART), following a 60-day course of a Traditional Chinese Medicine (TCM) recipe, specifically designed to regulate impulsiveness in order to modulate risk-taking behavior. The 14 participants recruited for this study were randomly assigned to the experimental and control groups and the TCM recipe (Panax, 520 mg; Astragalus membranaceous Bunge, 520 mg; Masnetitum, 840 mg; Ostrea gigas Thumb, 470 mg; Thinleaf Milkwort Root Radix Polygalae, 450 mg; and Os Draconis, 470 mg) was administered, as a diet supplement, to the seven participants in the experimental group. The neural activity of the two groups was monitored by a 3T MRI scanner, before and after the 60-day treatment. Associated with the improved advantageous risk-taking behavior seen in the experimental group, significantly stronger blood oxygenation level dependent (BOLD) responses were observed in the bilateral dorsolateral prefrontal cortex (DLPFC), left putamen, left thalamus, right insula, and right anterior cingulate cortex (ACC), regions which have previously been reported as being involved in risk-taking decision making. The effect of the TCM in improving advantageous risk-taking decision making appears to have been related to the enhanced efficiency of the cognitive affective system, the PFC–ACC–insula–striatum network, which functions to inhibit impulsiveness, to sensitize reward-related information, and to allow the opportunity, during risk estimation, to evaluate potential gains and losses. The findings of this study suggest that interventions acting on factors modulating risk-taking decision making could have a beneficial effect in terms of optimizing risk-taking behavior.     

Animal foraging and the evolution of goal-directed cognition

Foraging- and feeding-related behaviors across eumetazoans share similar molecular mechanisms, suggesting the early evolution of an optimal foraging behavior called area-restricted search (ARS), involving mechanisms of dopamine and glutamate in the modulation of behavioral focus. Similar mechanisms in the vertebrate basal ganglia control motor behavior and cognition and reveal an evolutionary progression toward increasing internal connections between prefrontal cortex and striatum in moving from amphibian to primate. The basal ganglia in higher vertebrates show the ability to transfer dopaminergic activity from unconditioned stimuli to conditioned stimuli. The evolutionary role of dopamine in the modulation of goal-directed behavior and cognition is further supported by pathologies of human goal-directed cognition, which have motor and cognitive dysfunction and organize themselves, with respect to dopaminergic activity, along the gradient described by ARS, from perseverative to unfocused. The evidence strongly supports the evolution of goal-directed cognition out of mechanisms initially in control of spatial foraging but, through increasing cortical connections, eventually used to forage for information.     

Acetylcholine actions in the dorsomedial striatum support the flexible shifting of response patterns

There is accumulating evidence that the dorsomedial striatum plays a significant role in the learning of a new response pattern and the inhibiting of old response patterns when conditions demand a shift in strategies. This paper proposes that activity of cholinergic neurons in the dorsomedial striatum is critical for enabling behavioral flexibility when there is a change in task contingencies. Recent experimental findings are provided supporting this idea. Measuring acetylcholine efflux from the dorsomedial striatum during the acquisition and reversal learning of a spatial discrimination shows that acetylcholine efflux selectively increases during reversal learning as a rat begins to learn a newly reinforced spatial location, but returns to near basal levels when a rat reliably executes the new choice pattern. Experimental findings are also described indicating that the blockade of muscarinic cholinergic receptors in the dorsomedial striatum does not impair acquisition of an egocentric response discrimination, but impairs reversal learning of an egocentric response discrimination. Based on these results, increased cholinergic activity at muscarinic receptors is part of a neurochemical process in the dorsomedial striatum that allows inhibition of a previously relevant response pattern while learning a new response pattern. In situations that demand behavioral flexibility, muscarinic cholinergic activity in the dorsomedial striatum may directly influence corticostriatal plasticity to produce changes in response patterns.     

Evidence for an antagonistic interaction between reward and punishment sensitivity on striatal activity: A verification of the Joint Subsystems Hypothesis

The Reinforcement Sensitivity Theory proposes that the Behavioral Approach System (BAS) comprises dopaminergic brain regions and underpins reward sensitivity causing impulsivity. It has been shown in a supraliminal priming task that highly reward sensitive subjects have a larger reaction time (RT) priming effect and make more commission errors to prime-incongruent targets. We adapted a similar task to event-related fMRI and hypothesized that (1) high reward sensitivity is associated with increased activation in dopaminergic brain regions, the ventral striatum in particular, (2) that BAS related personality traits predict impulsivity and (3) that the BAS effects are larger after adjusting for the interactive influence of trait avoidance, as predicted by the Joint Subsystems Hypothesis. Fourteen healthy females participated in the fMRI experiment and were scored on sensitivity to reward (SR) and trait avoidance, i.e., sensitivity to punishment (SP) and neuroticism (N). SR scores were adjusted by SP and N scores. As hypothesized, adjusted SR scores predicted, more than SR scores alone, activity in the ventral striatum (left caudate nucleus and nucleus accumbens). SR+/ SP− scores predicted increased impulsiveness, i.e., a right side RT priming effect. These results support the Joint Subsystems Hypothesis.     

Concurrent Movement Impairs Incidental But Not Intentional Statistical Learning

The effect of concurrent movement on incidental versus intentional statistical learning was examined in two experiments. In Experiment 1, participants learned the statistical regularities embedded within familiarization stimuli implicitly, whereas in Experiment 2 they were made aware of the embedded regularities and were instructed explicitly to learn these regularities. Experiment 1 demonstrated that while the control group were able to learn the statistical regularities, the resistance‐free cycling group and the exercise group did not demonstrate learning. This is in contrast with the findings of Experiment 2, where all three groups demonstrated significant levels of learning. The results suggest that the movement demands, rather than the physiological stress, interfered with statistical learning. We suggest movement activates the striatum, which is not only responsible for motor control but also plays a role in incidental learning.     

A forced-attention dichotic listening fMRI study on 113 subjects

We report fMRI and behavioral data from 113 subjects on attention and cognitive control using a variant of the classic dichotic listening paradigm with pairwise presentations of consonant-vowel syllables. The syllable stimuli were presented in a block-design while subjects were in the MR scanner. The subjects were instructed to pay attention to and report either the left or right ear stimulus. The hypothesis was that paying attention to the left ear stimulus (FL condition) induces a cognitive conflict, requiring cognitive control processes, not seen when paying attention to the right ear stimulus (FR condition), due to the perceptual salience of the right ear stimulus in a dichotic situation. The FL condition resulted in distinct activations in the left inferior prefrontal gyrus and caudate nucleus, while the right inferior frontal gyrus and caudate were activated in both the FL and FR conditions, and in a non-instructed (NF) baseline condition.     

Why won’t you do what I want? The informative failures of children and models

Computational models are powerful tools – too powerful, according to some. We argue that the idea that models can “do anything” is wrong, and we describe how their failures have been informative. We present new work showing surprising diversity in the effects of feedback on children's task-switching, such that some children perseverate despite this feedback, other children switch as instructed, and yet others play an “opposites” game without truly switching to the newly instructed task. We present simulations that demonstrate the failure of an otherwise-successful neural network model to capture this failure. Simulating this pattern motivates the inclusion of updating mechanisms that make contact with a growing literature on frontostriatal function, despite their absence in theories of the development of cognitive flexibility. We argue from this and other examples that computational models are more constrained than is typically acknowledged and that their resulting failures can be theoretically illuminating.     

Spermine improves recognition memory deficit in a rodent model of Huntington’s disease

Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with motor and cognitive impairment. Intrastriatal administration of quinolinic acid (QA) causes neurodegeneration, glial proliferation and cognitive impairment in animals, which are similar to these seen in human HD. Since polyamines improve memory in cognitive tasks, we now tested if the post-training intrastriatal administration of spermine, an agonist of the polyamine site at the NMDA receptor, reverses the deficits in the object recognition task induced by QA. Bilateral striatal injections of QA (180 or 360 nmol/site) caused object recognition impairment, neuronal death and reactive astrogliosis. A single injection of spermine (0.1 and 1 nmol/site), 5 days after QA injection, reversed QA-induced impairment of object recognition task. Spermine (0.1 nmol/site) also inhibited QA-induced reactive astrogliosis measured by a semi-quantitative determination of GFAP immunolabelling, but did not alter neuronal death, measured by a semi-quantitative determination of fluoro-Jade C staining. These results suggest that polyamine binding sites may be considered a novel therapeutic target to prevent reactive astrogliosis and mnemonic deficits in HD.     

Acetylcholine modulation of neural systems involved in learning and memory

Extensive evidence supports the view that cholinergic mechanisms modulate learning and memory formation. This paper reviews evidence for cholinergic regulation of multiple memory systems, noting that manipulations of cholinergic functions in many neural systems can enhance or impair memory for tasks generally associated with those neural systems. While parallel memory systems can be identified by combining lesions with carefully crafted tasks, most—if not all—tasks require the combinatorial participation of multiple neural systems. This paper offers the hypothesis that the magnitude of acetylcholine (ACh) release in different neural systems may regulate the relative contributions of these systems to learning. Recent studies of ACh release, obtained with in vivo microdialysis samples during training, together with direct injections of cholinergic drugs into different neural systems, provide evidence that release of ACh is important in engaging these systems during learning, and that the extent to which the systems are engaged is associated with individual differences in learning and memory.     

Computational models inform clinical science and assessment: An application to category learning in striatal-damaged patients

In this article we develop a new model of classification that is intermediate between the static, single strategy decision-bound models and the dynamic trial by trial multiple systems model, dCOVIS. The new model, referred to as the sCOVIS model, assumes hypothesis-testing and procedural-based subsystems are active on each trial, but that the parameters that govern behavior of the system are fixed (static) within a block of trials. To determine the clinical utility of the model, it was applied to nonlinear information-integration classification data from patients with Parkinson’s (PD) and Huntington’s disease (HD). In one application, the models suggest that the locus of HD patients’ nonlinear information-integration deficits is in their increased reliance on hypothesis-testing strategies, whereas the locus of PD patients’ deficit is in the application of sub-optimal procedural-based strategies. In a second application, the weight associated with the hypothesis-testing subsystem is shown to account for a significant amount of the variance in longitudinal cognitive decline in non-demented PD patients above and beyond that predicted by accuracy alone. Together, the accuracy rate and this model index account for 72% of the total variance associated with cognitive decline in this sample of PD patients. Interestingly, the Wisconsin Card Sort task added no additional predictive power above and beyond that predicted by nonlinear accuracy alone.