Overexpressing histone deacetylase 5 in rat dorsal striatum alters reward-guided decision-making and associated neural encoding

A broad range of decision-making processes involve gradual accumulation of evidence over time, but the neural circuits responsible for this computation are not yet established. Recent data indicate that cortical regions that are prominently associated with accumulating evidence, such as the posterior parietal cortex and the frontal orienting fields, may not be directly involved in this computation. Which, then, are the regions involved? Regions that are directly involved in evidence accumulation should directly influence the accumulation-based decision-making behavior, have a graded neural encoding of accumulated evidence and contribute throughout the accumulation process. Here, we investigated the role of the anterior dorsal striatum (ADS) in a rodent auditory evidence accumulation task using a combination of behavioral, pharmacological, optogenetic, electrophysiological and computational approaches. We find that the ADS is the first brain region known to satisfy the three criteria. Thus, the ADS may be the first identified node in the network responsible for evidence accumulation.

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Causal contribution and dynamical encoding in the striatum during evidence accumulation

10.1101/245316 ◽

2018 ◽

Cited By ~ 2

Author(s):

Michael M. Yartsev ◽

Timothy D. Hanks ◽

Alice M. Yoon ◽

Carlos D. Brody

Keyword(s):

Decision Making ◽

Posterior Parietal Cortex ◽

Dorsal Striatum ◽

Neural Encoding ◽

Evidence Accumulation ◽

Decision Making Processes ◽

Posterior Parietal ◽

Gradual Accumulation ◽

Cortical Regions ◽

Decision Making Behavior

A broad range of decision-making processes involve gradual accumulation of evidence over time, but the neural circuits responsible for this computation are not yet established. Recent data indicates that cortical regions prominently associated with accumulating evidence, such as posterior parietal cortex and the frontal orienting fields, are not necessary for computing it. Which, then, are the regions responsible? Regions directly involved in evidence accumulation should satisfy the criteria of being necessary for accumulation-based decision-making behavior, having a graded neural encoding of accumulated evidence and causal contributing throughout the accumulation process. Here, we investigated the role of the anterior dorsal striatum (ADS) in a rodent auditory evidence accumulation task using a combination of behavioral, pharmacological, optogenetic, electrophysiological and computational approaches. We find that the ADS is the first brain region known to satisfy these criteria. Thus, the ADS may be the first identified node in the network responsible for evidence accumulation.

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Neural activity in the dorsal striatum during cognitive decision making

Neuroscience Research ◽

10.1016/j.neures.2010.07.1328 ◽

2010 ◽

Vol 68 ◽

pp. e299

Author(s):

Satoshi Nonomura ◽

Kazuyuki Samejima ◽

Kenji Doya ◽

Jun Tanji

Keyword(s):

Decision Making ◽

Neural Activity ◽

Dorsal Striatum ◽

Cognitive Decision

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Neural encoding of perceived patch value during competitive and hazardous virtual foraging

Nature Communications ◽

10.1038/s41467-021-25816-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Brian Silston ◽

Toby Wise ◽

Song Qi ◽

Xin Sui ◽

Peter Dayan ◽

...

Keyword(s):

Decision Making ◽

Social Foraging ◽

Survival Strategy ◽

Neural Encoding ◽

Individual Level ◽

Hazardous Environments ◽

Predatory Attack ◽

Multidimensional Information ◽

Human Participants ◽

Foraging Task

AbstractNatural observations suggest that in safe environments, organisms avoid competition to maximize gain, while in hazardous environments the most effective survival strategy is to congregate with competition to reduce the likelihood of predatory attack. We probed the extent to which survival decisions in humans follow these patterns, and examined the factors that determined individual-level decision-making. In a virtual foraging task containing changing levels of competition in safe and hazardous patches with virtual predators, we demonstrate that human participants inversely select competition avoidant and risk diluting strategies depending on perceived patch value (PPV), a computation dependent on reward, threat, and competition. We formulate a mathematically grounded quantification of PPV in social foraging environments and show using multivariate fMRI analyses that PPV is encoded by mid-cingulate cortex (MCC) and ventromedial prefrontal cortices (vMPFC), regions that integrate action and value signals. Together, these results suggest humans utilize and integrate multidimensional information to adaptively select patches highest in PPV, and that MCC and vMPFC play a role in adapting to both competitive and predatory threats in a virtual foraging setting.

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Distinct but Synergistic Roles for Histone Deacetylase in the Dorsal Striatum During Habit Formation

Biological Psychiatry ◽

10.1016/j.biopsych.2018.06.020 ◽

2018 ◽

Vol 84 (5) ◽

pp. 322-323

Author(s):

Christopher Pittenger ◽

Jane R. Taylor

Keyword(s):

Histone Deacetylase ◽

Habit Formation ◽

Dorsal Striatum

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S146. ASSOCIATION OF IMPAIRED MODEL-FREE DECISION-MAKING WITH ABERRANT STRIATAL DOPAMINE, BRAIN ACTIVATION, AND COGNITIVE DIFFICULTIES IN PATIENTS WITH SCHIZOPHRENIA DURING PSYCHOTIC REMISSION

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.212 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S91-S92

Author(s):

Felix Brandl ◽

Mihai Avram ◽

Jorge Cabello ◽

Mona Mustafa ◽

Claudia Leucht ◽

...

Keyword(s):

Decision Making ◽

Cognitive Impairments ◽

Dorsal Striatum ◽

Striatal Dopamine ◽

Dopamine Synthesis ◽

Cognitive Difficulties ◽

Model Based ◽

Model Free ◽

Trail Making ◽

Task Activation

Abstract Background Human decision-making ranges between the extremes of automatic and fast model-free behavior (i.e., relying only on previous outcomes) and more flexible, but computationally demanding model-based behavior (i.e., implementing cognitive models). Model-based/model-free decision-making can be investigated using sequential decision tasks and has been shown to be associated with presynaptic striatal dopamine synthesis. During phases of psychotic remission in schizophrenia, dopamine synthesis in the dorsal striatum is reduced. We hypothesized that particularly model-free decision-making is impaired in schizophrenia during psychotic remission and is associated with (i) abnormal dopamine synthesis in dorsal striatum, (ii) aberrant task-activation in dorsal striatum, and (iii) cognitive difficulties in patients (e.g., reduced speed). Methods 26 patients with chronic schizophrenia, currently in psychotic remission, and 22 healthy controls (matched by age and gender) were enrolled in the study. Model-based/model-free decision-making was evaluated with a two-stage Markov decision task, followed by computational modeling of subjects’ learning behavior. Presynaptic dopamine synthesis was assessed by 18F-DOPA positron emission tomography and subsequent graphical Patlak analysis. Task-activation was measured by functional magnetic resonance imaging. Cognitive impairments were quantified by Trail-Making-Test A (among others). Associations between decision-making parameters, dopamine synthesis, task-activation, and cognitive impairments were tested by correlation analyses. Results Patients with schizophrenia showed selectively impaired model-free decision-making. 18F-DOPA uptake (i.e., presynaptic dopamine synthesis capacity) in the dorsal striatum was decreased in patients. Impaired model-free decision-making in patients correlated with (i) decreased dopamine synthesis in dorsal striatum, (ii) abnormal task-activation in dorsal striatum, and (iii) lower speed in Trail-Making-Test A. Discussion Results demonstrate an association of reduced dorsal striatal dopamine synthesis and brain activity with impaired model-free decision-making in schizophrenia, which potentially contributes to cognitive difficulties.

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Focused ultrasound enhances sensorimotor decision-making in monkeys

10.1101/041152 ◽

2016 ◽

Cited By ~ 2

Author(s):

Matthew E Downs ◽

Tobias Teichert ◽

Amanda Buch ◽

Maria Eleni Karakatsani ◽

Carlos Sierra ◽

...

Keyword(s):

Decision Making ◽

Focused Ultrasound ◽

Dorsal Striatum ◽

Decision Criterion ◽

Clinical Tool ◽

Noninvasive Brain Stimulation ◽

Integral Role ◽

Potential Applications ◽

Sensory Evidence ◽

Decision Making Behavior

AbstractNoninvasive brain stimulation using focused ultrasound has many potential applications as a research and clinical tool. Here, we investigated the effect of focused ultrasound (FUS) combined with systemically administered microbubbles on visual-motor decision-making behavior in monkeys. We applied FUS to the putamen in one hemisphere to open the blood-brain barrier, and then tested behavioral performance 3-4 hours later. On days when the monkeys were treated with FUS, their decisions were faster and more accurate than days without sonication. The performance improvement suggested both a shift in the decision criterion and an enhancement of the use of sensory evidence in the decision process. FUS also interacted with the effect of a low dose of haloperidol. The results suggest that a two-minute application of FUS can have a sustained impact on performance of complex cognitive tasks, and may increase the efficacy of psychoactive medications. The results lend further support to the idea that the dorsal striatum plays an integral role in evidence- and reward-based decision-making.

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Long Term Study of Motivational and Cognitive Effects of Low-intensity Focused Ultrasound Neuromodulation in the Dorsal Striatum of Nonhuman Primates

10.1101/2021.06.30.450605 ◽

2021 ◽

Author(s):

Fabian Munoz ◽

Anna Meaney ◽

Aliza Gross ◽

Katherine Liu ◽

Antonios N Pouliopoulos ◽

...

Keyword(s):

Decision Making ◽

Brain Stimulation ◽

Nonhuman Primates ◽

Focused Ultrasound ◽

Dorsal Striatum ◽

Behavioral Impairment ◽

Decision Accuracy ◽

Long Term Study ◽

Deep Brain

Noninvasive brain stimulation using focused ultrasound (FUS) has many potential applications as a research and clinical tool, including incorporation into neural prosthetics for cognitive rehabilitation. To develop this technology, it is necessary to evaluate the safety and efficacy of FUS neuromodulation for specific brain targets and cognitive functions. It is also important to test whether repeated long-term application of FUS to deep brain targets improves or degrades behavioral and cognitive function. To this end, we investigated the effects of FUS in the dorsal striatum of nonhuman primates (NHP) performing a visual-motor decision-making task for small or large rewards. Over the course of 2 years, we performed 129 and 147 FUS applications, respectively, in two NHP. FUS (0.5 MHz @ 0.2 - 0.8 MPa) was applied to the putamen and caudate in both hemispheres to evaluate the effects on movement accuracy, motivation, decision accuracy, and response time. Sonicating the caudate or the putamen unilaterally resulted in modest but statistically significant improvements in motivation and decision accuracy, but at the cost of slower reaction times. The effects were dose (i.e., FUS pressure) and reward dependent. There was no effect on reaching accuracy, nor was there long-term behavioral impairment or neurological trauma evident on T1-weighted, T2-weighted, or susceptibility-weighted MRI scans. Sonication also resulted in significant changes in resting state functional connectivity between the caudate and multiple cortical regions. The results indicate that applying FUS to the dorsal striatum can positively impact the motivational and cognitive aspects of decision making. The capability of FUS to improve motivation and cognition in NHPs points to its therapeutic potential in treating a wide variety of human neural diseases, and warrants further development as a novel technique for non-invasive deep brain stimulation.

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