Differences between Neural Activity in Prefrontal Cortex and Striatum during Learning of Novel Abstract Categories

Learning to classify diverse experiences into meaningful groups, like categories, is fundamental to normal cognition. To understand its neural basis, we simultaneously recorded from multiple electrodes in lateral prefrontal cortex and dorsal striatum, two interconnected brain structures critical for learning. Each day, monkeys learned to associate novel abstract, dot-based categories with a right versus left saccade. Early on, when they could acquire specific stimulus-response associations, striatum activity was an earlier predictor of the corresponding saccade. However, as the number of exemplars increased and monkeys had to learn to classify them, PFC activity began to predict the saccade associated with each category before the striatum. While monkeys were categorizing novel exemplars at a high rate, PFC activity was a strong predictor of their corresponding saccade early in the trial before the striatal neurons. These results suggest that striatum plays a greater role in stimulus-response association and PFC in abstraction of categories.Simons FoundationHardy, RichardHardy, LindaNational Institute of Mental Health (U.S.) (5RC1MH088316-02

Dynamic Social Adaptation of Motion-Related Neurons in Primate Parietal Cortex

Social brain function, which allows us to adapt our behavior to social context, is poorly understood at the single-cell level due largely to technical limitations. But the questions involved are vital: How do neurons recognize and modulate their activity in response to social context? To probe the mechanisms involved, we developed a novel recording technique, called multi-dimensional recording, and applied it simultaneously in the left parietal cortices of two monkeys while they shared a common social space. When the monkeys sat near each other but did not interact, each monkey's parietal activity showed robust response preference to action by his own right arm and almost no response to action by the other's arm. But the preference was broken if social conflict emerged between the monkeys—specifically, if both were able to reach for the same food item placed on the table between them. Under these circumstances, parietal neurons started to show complex combinatorial responses to motion of self and other. Parietal cortex adapted its response properties in the social context by discarding and recruiting different neural populations. Our results suggest that parietal neurons can recognize social events in the environment linked with current social context and form part of a larger social brain network

Learning Visual-Motor Cell Assemblies for the iCub Robot using a Neuroanatomically Grounded Neural Network

In this work we describe how an existing neural model for learning Cell Assemblies (CAs) across multiple neuroanatomical brain areas has been integrated with a humanoid robot simulation to explore the learning of associations of visual and motor modalities. The results show that robust CAs are learned to enable pattern completion to select a correct motor response when only visual input is presented. We also show, with some parameter tuning and the pre-processing of more realistic patterns taken from images of real objects and robot poses the network can act as a controller for the robot in visuo-motor association tasks. This provides the basis for further neurorobotic experiments on grounded language learning

Cognitive Flexibility and Academic Performance in College Students with ADHD: An fMRI Study

Cognitive flexibility, or the ability to change behavior or cognitive action appropriately in response to context shifts, is crucial to college-level learning, as it is needed for solving problems that require a transfer of familiar knowledge to novel concepts. Cognitive flexibility is known to involve neural areas concentrated in the frontal lobes, such as the inferior and superior frontal gyri and the anterior cingulate cortex, but the activation of this network is typically weaker in the ADHD population. In academic settings, individuals with ADHD tend to perform below healthy peers, have lower GPAs, are more likely to be on academic probation, and have decreased motivation. While most of these downfalls are attributed to attentional deficits, no investigations have been done to assess any effects of cognitive flexibility on academic performance. Therefore, this study used the Wisconsin Card Sorting Task (WCST) in the fMRI to assess cognitive flexibility in college students with and without ADHD and compared task performance to academic performance to determine if there is any relationship. We found that the ADHD group presented more perseverative errors on the WCST, and this performance was negatively correlated to GPA, suggesting that cognitive flexibility deficits impair academic performance. We also observed decreased activation of the anterior cingulate cortex and inferior and superior frontal gyri in subjects with ADHD as compared to controls, suggesting a possible neural network involved in these behavioral deficits

Variables influencing the neural correlates of perceived risk of physical harm

Abstract Many human activities involve a risk of physical harm. However, not much is known about the specific brain regions involved in decision making regarding these risks. To explore the neural correlates of risk perception for physical harms, 19 participants took part in an event-related fMRI study while rating risky activities. The scenarios varied in level of potential harm (e.g., paralysis vs. stubbed toe), likelihood of injury (e.g., 1 chance in 100 vs. 1 chance in 1,000), and format (frequency vs. probability). Networks of brain regions were responsive to different aspects of risk information. Cortical language-processing areas, the middle temporal gyrus, and a region around the bed nucleus of stria terminalis responded more strongly to high-harm conditions. Prefrontal areas, along with subcortical ventral striatum, responded preferentially to highlikelihood conditions. Participants rated identical risks to be greater when information was presented in frequency format rather than probability format. These findings indicate that risk assessments for physical harm engage a broad network of brain regions that are sensitive to the severity of harm, the likelihood of risk, and the framing of risk information

The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: update to the study protocol and detailed statistical analysis plan (SAP)

Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500 mg four times daily and placebo or orally administered 500 mg of flucloxacillin four times daily and phenoxymethylpenicillin 500 mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias

Modulation of neural responses in inferotemporal cortex during the interpretation of ambiguous photographs

Ambiguous images are interpreted in the context of biases about what they might be; these biases and the behavioral consequences induced by them may influence the processing of images. In this report, we examine neural responses in inferotemporal cortex (IT) during the interpretation of ambiguous photographs created by morphing between two photographs. Monkeys classified different images as being one of two choices and learned to classify most of the samples correctly. For one image (the ambiguous sample) reward was administered randomly for either possible choice, and the monkeys were free to classify that image based on their own interpretation, with no learning possible. The ambiguous samples were not classified randomly: the monkey interpreted the samples differently during different sessions. The interpretation of the ambiguous sample was, in turn, highly correlated with the normalized response of individual neurons in IT to the ambiguous sample. If an ambiguous sample was interpreted as a particular choice during a session, the response to that ambiguous sample more closely resembled the response to that choice. Identical ambiguous images were interpreted differently during different sessions, and neural responses reflected the differing interpretations of the image during that session. The relationship between the interpretation of the image and neural responses strengthened over the course of a session because neural responses shifted to more closely resemble the response to the initial interpretation of the image. The data support a flexible representation of visual stimuli in higher visual areas