Striatum-projecting prefrontal cortex neurons support working memory maintenance

ABSTRACTThe medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC→dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC→dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC→dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the delay— alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of >50% mPFC→dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

Effect of timing of school enrollment on physical fitness in third graders

Timing of school enrollment may vary considerably due to children who were enrolled early / delayed or skipped / repeated a school year. Accordingly, the age range within school grades includes older-than-keyage (OTK) and younger-than-keyage (YTK) children. Studies examining academic performance of OTK and YTK children versus keyage children reported large differences in academic performance. However, there are no studies available that examined physical fitness of OTK and YTK versus keyage children. The aim of this study was to compare physical fitness of OTK (N = 25,086) and YTK (N = 1,885) children versus keyage children (N = 108,295) in a sample of German third graders. Physical fitness tests comprised cardiorespiratory endurance, coordination, speed, lower, and upper limbs muscle power. Predictions of physical fitness performance for YTK and OTK children were estimated using data from keyage children by taking age, sex, school, and cohort into account. The difference between observed and predicted z-scores yielded a delta z-score that was used as a dependent variable in the linear mixed models. Findings indicate that OTK children showed impaired performance compared to keyage children, especially in coordination, and that YTK children outperformed keyage children, especially in coordination. Teachers should be aware that despite their age advantage, OTK children often show impaired fitness compared to keyage children.

Smoking as a Common Modulator of Sensory Gating and Reward Learning in Individuals with Psychotic Disorders

Motivational and perceptual disturbances co-occur in psychosis and have been linked to aberrations in reward learning and sensory gating, respectively. Although traditionally studied independently, when viewed through a predictive coding framework, these processes can both be linked to dysfunction in striatal dopaminergic prediction error signaling. This study examined whether reward learning and sensory gating are correlated in individuals with psychotic disorders, and whether nicotine—a psychostimulant that amplifies phasic striatal dopamine firing—is a common modulator of these two processes. We recruited 183 patients with psychotic disorders (79 schizophrenia, 104 psychotic bipolar disorder) and 129 controls and assessed reward learning (behavioral probabilistic reward task), sensory gating (P50 event-related potential), and smoking history. Reward learning and sensory gating were correlated across the sample. Smoking influenced reward learning and sensory gating in both patient groups; however, the effects were in opposite directions. Specifically, smoking was associated with improved performance in individuals with schizophrenia but impaired performance in individuals with psychotic bipolar disorder. These findings suggest that reward learning and sensory gating are linked and modulated by smoking. However, disorder-specific associations with smoking suggest that nicotine may expose pathophysiological differences in the architecture and function of prediction error circuitry in these overlapping yet distinct psychotic disorders.

What Language Disorders Reveal About the Mechanisms of Morphological Processing

We addressed an understudied topic in the literature of language disorders, that is, processing of derivational morphology, a domain which requires integration of semantic and syntactic knowledge. Current psycholinguistic literature suggests that word processing involves morpheme recognition, which occurs immediately upon encountering a complex word. Subsequent processes take place in order to interpret the combination of stem and affix. We investigated the abilities of individuals with agrammatic (PPA-G) and logopenic (PPA-L) variants of primary progressive aphasia (PPA) and individuals with stroke-induced agrammatic aphasia (StrAg) to process pseudowords which violate either the syntactic (word class) rules (*reheavy) or the semantic compatibility (argument structure specifications of the base form) rules (*reswim). To this end, we quantified aspects of word knowledge and explored how the distinct deficits of the populations under investigation affect their performance. Thirty brain-damaged individuals and 10 healthy controls participated in a lexical decision task. We hypothesized that the two agrammatic groups (PPA-G and StrAg) would have difficulties detecting syntactic violations, while no difficulties were expected for PPA-L. Accuracy and Reaction Time (RT) patterns indicated: the PPA-L group made fewer errors but yielded slower RTs compared to the two agrammatic groups which did not differ from one another. Accuracy rates suggest that individuals with PPA-L distinguish *reheavy from *reswim, reflecting access to and differential processing of syntactic vs. semantic violations. In contrast, the two agrammatic groups do not distinguish between *reheavy and *reswim. The lack of difference stems from a particularly impaired performance in detecting syntactic violations, as they were equally unsuccessful at detecting *reheavy and *reswim. Reduced grammatical abilities assessed through language measures are a significant predictor for this performance, suggesting that the “hardware” to process syntactic information is impaired. Therefore, they can only judge violations semantically where both *reheavy and *reswim fail to pass as semantically ill-formed. This finding further suggests that impaired grammatical knowledge can affect word level processing as well. Results are in line with the psycholinguistic literature which postulates the existence of various stages in accessing complex pseudowords, highlighting the contribution of syntactic/grammatical knowledge. Further, it points to the worth of studying impaired language performance for informing normal language processes.

Validation of Discrete and Regression-Based Performance and Cognitive Fatigability Normative Data for the Paced Auditory Serial Addition Test in Multiple Sclerosis

Cognitive fatigability is an objective performance decrement that occurs over time during a task requiring sustained cognitive effort. Although cognitive fatigability is a common and debilitating symptom in multiple sclerosis (MS), there is currently no standard for its quantification. The objective of this study was to validate the Paced Auditory Serial Addition Test (PASAT) discrete and regression-based normative data for quantifying performance and cognitive fatigability in an Ontario-based sample of individuals with MS. Healthy controls and individuals with MS completed the 3″ and 2″ versions of the PASAT. PASAT performance was measured with total correct, dyad, and percent dyad scores. Cognitive fatigability scores were calculated by comparing performance on the first half (or third) of the task to the last half (or third). The results revealed that the 3″ PASAT was sufficient to detect impaired performance and cognitive fatigability in individuals with MS given the increased difficulty of the 2″ version. In addition, using halves or thirds for calculating cognitive fatigability scores were equally effective methods for detecting impairment. Finally, both the discrete and regression-based norms classified a similar proportion of individuals with MS as having impaired performance and cognitive fatigability. These newly validated discrete and regression-based PASAT norms provide a new tool for clinicians to document statistically significant cognitive fatigability in their patients.

Saccadic Eye Movements in Elderly Depressed Patients With Suicidal Behaviors: An Exploratory Eye-Tracking Study

Suicidal behaviors (SBs) are often associated with impaired performance on neuropsychological executive functioning (EF) measures that encourage the development of more specific and reliable tools. Recent evidence could suggest that saccadic movement using eye tracking can provide reliable information on EF in depressive elderly. The aim of this study was to describe oculomotor performances in elderly depressed patients with SB. To achieve this aim, we compared saccadic eye movement (SEM) performances in elderly depressed patients (N = 24) with SB and with no SB in prosaccade (PS) and antisaccade (AS) tasks under the gap, step, and overlap conditions. All participants also underwent a complete neuropsychological battery. Performances were impaired in patients with SB who exhibited less corrected AS errors and longer time to correct them than patients with no SB. Moreover, both groups had a similar performance for PS latencies and correct AS. These preliminary results suggested higher cognitive inflexibility in suicidal patients compared to non-suicidal. This inflexibility may explain the difficulty of the depressed elderly in generating solutions to the resurgence of suicidal ideation (SI) to respond adequately to stressful environments. The assessment of eye movement parameters in depressed elderly patients may be a first step in identifying high-risk patients for suicide.

Quantitative MRI and Clinical Assessment of Muscle Function in Adults With Cerebral Palsy

Aim: To relate quantitative magnetic resonance imaging (MRI) of ankle plantar flexor muscles to clinical functional tests in adults with cerebral palsy (CP) and neurologically intact (NI) adults.Methods: Eleven adults with CP (aged 41 ± 12, GMFCS level I-II) and 11 NI adults (aged 35 ± 10) participated in this case-control study. We used MRI to assess muscle volume and composition of the triceps surae muscles. We quantified muscle function as maximal voluntary plantarflexion (MVC) torque and countermovement jump (CMJ) height.Results: Compared to NI adults, the MRI intramuscular fat fraction estimate was significantly higher and MRI muscle volume and functional abilities (MVC and CMJ) significantly lower in adults with CP. In NI adults, but not adults with CP, MRI muscle volume correlated significantly with MVC and CMJ. In adults with CP, the estimate of intramuscular fat levels correlated significantly with jump height in a CMJ.Discussion: This study shows reduced muscle volume and altered muscle composition in adults with CP. Muscle composition appears to provide a better marker than muscle volume of reduced muscle function and impaired performance in this population. Measurements of muscle composition could be used in the assessment of neuromuscular impairments and in the determination of rehabilitation protocols in individuals with neurological disorders.

Visuospatial working memory and the construction of a spatial situation model in listening comprehension: An examination using a spatial tapping task

The present study investigated how visuospatial working memory (VSWM) is involved in the construction of a spatial situation model for spatial passages presented auditorily. A simple spatial tapping condition, a complex tapping condition as a target-tracking task, and a control condition, were used to analyze the role of VSWM. To understand how individuals who differ in verbal working memory (VWM) capacity (determined with a listening span test) process spatial text during dual-task performance, individual differences in VWM capacity were analyzed. In two experiments, the participants listened to a spatial text at the same time as performing a spatial concurrent task or no concurrent task. The results of the free recall test in Experiment 1 showed that there were no differences between the tapping conditions in the high VWM capacity group; the low VWM capacity group had a lower performance in both spatial tapping tasks compared to the control condition. The results of the map drawing test in Experiment 2 showed that complex spatial tapping impaired performance in comparison to simple spatial tapping and the control condition in the high VWM capacity group; in the low VWM capacity group, both spatial tapping tasks impaired recall performance. In addition, the participants with high VWM capacity demonstrated better performance. Overall, the results suggest that individuals with high VWM capacity have more resources to process verbal and spatial information than those with low VWM capacity, indicating that VWM capacity is related to the degree of the involvement of VSWM.

Rumination Derails Reinforcement Learning With Possible Implications for Ineffective Behavior

How does rumination affect reinforcement learning—the ubiquitous process by which people adjust behavior after error to behave more effectively in the future? In a within-subjects design ( N = 49), we tested whether experimentally manipulated rumination disrupts reinforcement learning in a multidimensional learning task previously shown to rely on selective attention. Rumination impaired performance, yet unexpectedly, this impairment could not be attributed to decreased attentional breadth (quantified using a decay parameter in a computational model). Instead, trait rumination (between subjects) was associated with higher decay rates (implying narrower attention) but not with impaired performance. Our task-performance results accord with the possibility that state rumination promotes stress-generating behavior in part by disrupting reinforcement learning. The trait-rumination finding accords with the predictions of a prominent model of trait rumination (the attentional-scope model). More work is needed to understand the specific mechanisms by which state rumination disrupts reinforcement learning.

Health, performance and soiling of breeding does and their kits kept in two different housing systems on a German rabbit farm

<p>The aim of the present study was to compare a new housing (NC) for rabbit does and their kits that complies with German welfare regulations with established wire mesh cages (CC) on a commercial rabbit farm. Rabbit does were single-housed from five days antepartum until weaning at 31 d postpartum either in large pens (80×80 cm with an open top) with slatted plastic flooring (11 mm slats and 11 mm gaps), nestbox, elevated platform (15% perforated) and different manipulable materials (NC) or in cages (70×50×30 cm) with wire mesh flooring (12×70 mm holes and 3 mm wire diameter), nestbox and one gnawing stick (CC). Skin lesions, weight development, fertility, morbidity, cleanliness and kit performance of 272 rabbit does in a total of six batches were investigated. While there was no difference in performance of their kits, rabbit does showed an impaired performance with less weight gain and less body weight at weaning, lower fertility, more injuries and a higher incidence of mastitis and diarrhoea at the end of the rearing period in NC housing compared to CC housing. Additionally, soiling of hind feet was higher in NC than in CC housing. Overall, the poor hygienic conditions may have affected the animals’ health and make an improvement in the new housing system necessary, especially with regard to the floor design.</p>