Background: The neural bases of decision-making and contextual sensory discriminations have traditionally been studied in primates, highlighting the role of the prefrontal cortex in cognitive control and flexibility. With the advent of molecular tools to manipulate and monitor neuronal activity, these processes have increasingly been studied in rodents. However, rodent tasks typically consist of two-alternative forced choice paradigms that usually feature coarse sensory discriminations and no contextual dependence, limiting prefrontal involvement in task performance.
View Article and Find Full Text PDFDepression is highly comorbid among individuals with Parkinson's Disease (PD), who often experience unique challenges to accessing and benefitting from empirically supported interventions like Cognitive Behavioral Therapy (CBT). Given the role of reward processing in both depression and PD, this study analyzed a subset (N = 25) of participants who participated in a pilot telemedicine intervention of PD-informed CBT, and also completed a Reward- and Punishment-Learning Task (RPLT) at baseline. At the conclusion of CBT, participants were categorized into treatment responders (n = 14) and non-responders (n = 11).
View Article and Find Full Text PDFThe cognitive impact of psychological trauma can manifest as a range of post-traumatic stress symptoms that are often attributed to impairments in learning from positive and negative outcomes, aka reinforcement learning. Research on the impact of trauma on reinforcement learning has mainly been inconclusive. This study aimed to circumscribe the impact of psychological trauma on reinforcement learning in the context of neural response in time and frequency domains.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental problems with various genetic and environmental components. The ASD diagnosis is based on symptom expression without reliance on any biomarkers. The genetic contributions in ASD remain elusive.
View Article and Find Full Text PDFForaging entails a complex balance between approach and avoidance alongside sensorimotor and homeostatic processes under the control of multiple cortical and subcortical areas. Recently, it has become clear that several thalamic nuclei located near the midline regulate motivated behaviors. However, one midline thalamic nucleus that projects to key nodes in the foraging network, the central medial thalamic nucleus (CMT), has received little attention so far.
View Article and Find Full Text PDFAnxiety spectrum disorders are characterized by excessive and uncontrollable worrying about potential negative events in the short- and long-term future. Various reports linked anxiety spectrum disorders with working memory (WM) deficits despite conflicting results stemming from different study approaches. It remains unclear, however, how different anxiety spectrum disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD), differ in WM function.
View Article and Find Full Text PDFDysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons.
View Article and Find Full Text PDFDepression can occur due to common major life transitions, such as giving birth, menopause, retirement, empty-nest transition, and midlife crisis. Although some of these transitions are perceived as positive (e.g.
View Article and Find Full Text PDFNeuropathic pain is a subset of chronic pain that is caused by neurons that are damaged or firing aberrantly in the peripheral or central nervous systems. The treatment guidelines for neuropathic pain include antidepressants, calcium channel α delta ligands, topical therapy, and opioids as a second-line option. Pharmacotherapy has not been effective in the treatment of neuropathic pain except in the treatment of trigeminal neuralgia with carbamazepine.
View Article and Find Full Text PDFIn this review, we discuss the genetic etiologies of Alzheimer's disease (AD). Furthermore, we review genetic links to protein signaling pathways as novel pharmacological targets to treat AD. Moreover, we also discuss the clumps of AD-m ediated genes according to their single nucleotide polymorphism mutations.
View Article and Find Full Text PDFBackground And Objectives: Asymmetric onset of motor symptoms in PD can affect cognitive function. We examined whether motor-symptom laterality could affect feedback-based associative learning and explored its underlying neural mechanism by functional magnetic resonance imaging in PD patients.
Methods: We recruited 63 early-stage medication-naïve PD patients (29 left-onset medication-naïve patients, 34 right-onset medication-naïve patients) and 38 matched normal controls.
Major depressive disorder (MDD) is the most common non-motor manifestation of Parkinson's disease (PD) affecting 50% of patients. However, little is known about the cognitive correlates of MDD in PD. Using a computer-based cognitive task that dissociates learning from positive and negative feedback, we tested four groups of subjects: (1) patients with PD with comorbid MDD, (2) patients with PD without comorbid MDD, (3) matched patients with MDD alone (without PD), and (4) matched healthy control subjects.
View Article and Find Full Text PDFAnxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic anxiety disorder (PAD), are a group of common psychiatric conditions. They are characterized by excessive worrying, uneasiness, and fear of future events, such that they affect social and occupational functioning. Anxiety disorders can alter behavior and cognition as well, yet little is known about the particular domains they affect.
View Article and Find Full Text PDFLithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function.
View Article and Find Full Text PDFWe recorded basolateral amygdala (BL) neurons in a seminaturalistic foraging task. Rats had to leave their nest to retrieve food in an elongated arena inhabited by a mechanical predator. There were marked trial-to-trial variations in behavior.
View Article and Find Full Text PDFPrevious research has shown that trial ordering affects cognitive performance, but this has not been tested using category-learning tasks that differentiate learning from reward and punishment. Here, we tested two groups of healthy young adults using a probabilistic category learning task of reward and punishment in which there are two types of trials (reward, punishment) and three possible outcomes: (1) positive feedback for correct responses in reward trials; (2) negative feedback for incorrect responses in punishment trials; and (3) no feedback for incorrect answers in reward trials and correct answers in punishment trials. Hence, trials without feedback are ambiguous, and may represent either successful avoidance of punishment or failure to obtain reward.
View Article and Find Full Text PDFTo test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization.
View Article and Find Full Text PDFOne barrier to interpreting past studies of cognition and major depressive disorder (MDD) has been the failure in many studies to adequately dissociate the effects of MDD from the potential cognitive side effects of selective serotonin reuptake inhibitors (SSRIs) use. To better understand how remediation of depressive symptoms affects cognitive function in MDD, we evaluated three groups of subjects: medication-naïve patients with MDD, medicated patients with MDD receiving the SSRI paroxetine, and healthy control (HC) subjects. All were administered a category-learning task that allows for dissociation between learning from positive feedback (reward) vs.
View Article and Find Full Text PDFTo better understand how medication status and task demands affect cognition in major depressive disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the selective serotonin reuptake inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning.
View Article and Find Full Text PDFEmpirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex.
View Article and Find Full Text PDFBackground/aims: Levodopa and dopamine agonists have different effects on the motor, cognitive, and psychiatric aspects of Parkinson's disease (PD).
Methods: Using a computational model of basal ganglia (BG) and prefrontal cortex (PFC) dopamine, we provide a theoretical synthesis of the dissociable effects of these dopaminergic medications on brain and cognition. Our model incorporates the findings that levodopa is converted by dopamine cells into dopamine, and thus activates prefrontal and striatal D(1) and D(2) dopamine receptors, whereas antiparkinsonian dopamine agonists directly stimulate D(2) receptors in the BG and PFC (although some have weak affinity to D(1) receptors).
Building on our previous neurocomputational models of basal ganglia and hippocampal region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson's disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy.
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