Basal Ganglia Preferentially Encode Context Dependent Choice in a Two-Armed Bandit Task

Decision is a self-generated phenomenon, which is hard to track with standard time averaging methods, such as peri-event time histograms (PETHs), used in behaving animals. Reasons include variability in duration of events within a task and uneven reaction time of animals. We have developed a temporal normalization method where PETHs were juxtaposed all along task events and compared between neurons. We applied this method to neurons recorded in striatum and GPi of behaving monkeys involved in a choice task. We observed a significantly higher homogeneity of neuron activity profile distributions in GPi than in striatum. Focusing on the period of the task during which the decision was taken, we showed that approximately one quarter of all recorded neurons exhibited tuning functions. These so-called coding neurons had average firing rates that varied as a function of the value of both presented cues, a combination here referred to as context, and/or value of the chosen cue. The tuning functions were used to build a simple maximum likelihood estimation model, which revealed that (i) GPi neurons are more efficient at encoding both choice and context than striatal neurons and (ii) context prediction rates were higher than those for choice. Furthermore, the mutual information between choice or context values and decision period average firing rate was higher in GPi than in striatum. Considered together, these results suggest a convergence process of the global information flow between striatum and GPi, preferentially involving context encoding, which could be used by the network to perform decision-making

Single Medial Prefrontal Neurons Cope with Error

Learning from mistakes is a key feature of human behavior. However, the mechanisms underlying short-term adaptation to erroneous action are still poorly understood. One possibility relies on the modulation of attentional systems after an error. To explore this possibility, we have designed a Stroop-like visuo-motor task in monkeys that favors incorrect action. Using this task, we previously found that single neurons recorded from the anterior cingulate cortex (ACC) were closely tuned to behavioral performance and, more particularly, that the activity of most neurons was biased towards the evaluation of erroneous action. Here we describe single neurons engaged in both error detection and response alertness processing, whose activation is closely associated with the improvement of subsequent behavioral performance. Specifically, we show that the effect of a warning stimulus on neuronal firing is enhanced after an erroneous response rather than a successful one and that this outcome is correlated with an error rate decrease. Our results suggest that the anterior cingulate cortex, which exhibits this activity, serves as a powerful computational locus for rapid behavioral adaptation

Sleep

Study objective: To test the effects of coffee and napping on nocturnal driving in young and middle-aged participants. Design: A cup of coffee (200 mg of caffeine), a placebo (decaffeinated coffee, 15 mg of caffeine), or a 30-minute nap were tested. Participants drove 125 highway miles between 18:00 and 19:30 and between 02:00 and 03:30 after coffee, placebo, or a nap. Setting: Sleep laboratory and open French highway. Participants: Twelve young (range, 20-25 years) and 12 middle-aged participants (range, 40-50 years). Measurements: Inappropriate line crossings, self-perceived fatigue and sleepiness, and polysomnographic recordings were analyzed. Results: Compared to daytime, after placebo the number of inappropriate line crossings was significantly increased (2 versus 73 for young participants, P < 0.01 and 0 versus 76 for the middle-aged participants, P < 0.05). Both coffee and napping reduced the risk of inappropriate line crossings, compared with placebo, in young participants (respectively, by three-quarters, incidence rate ratios [IRR] = 0.26 95% confidence interval [CI], 0.09-0.74, P < 0.05 and by two thirds, IRR = 0.34 95% CI, 0.20-0.58, P < 0.001) and in middle-aged participants (respectively by nine tenths, IRR = 0.11 95% CI, 0.05-0.21, P < 0.001 and by one fifth, IRR = 0.77 95% CI, 0.63-0.95, P < 0.05). A significant interaction between age and condition (IRR = 2.27 95% CI, 1.28-4.16 P < 0.01) showed that napping led to fewer inappropriate line crossings in younger participants than in middle-aged participants. During napping, young participants slept more (P < 0.01) and had more delta sleep (P < 0.05) than middle-aged participants. Self-perceived sleepiness and fatigue did not differ in both age groups, but coffee improved sleepiness (P < 0.05), whereas napping did not. Conclusions: Coffee significantly improves performance in young and middle-aged participants. Napping is more efficient in younger than in older participants. Countermeasures to sleepiness should be adapted according to the age of drivers

Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics

BACKGROUND:Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, alpha-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. METHODS AND FINDINGS:The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that alpha-flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, alpha-flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by alpha-flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by alpha-flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, alpha-flupentixol failed to induce EPS and to alter STN neuronal activity. CONCLUSION:Our study reports strong evidence to show that hypokinesia and catalepsy induced by alpha-flupentixol are triggered by dramatic changes occurring in basal ganglia network. We provide new insight into the key role of GP in the pathophysiology of APD-induced EPS suggesting that the GP can be considered as a potential target for the treatment of EPS

Extended Driving Impairs Nocturnal Driving Performances

Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3–5am, 1–5am and 9pm–5am) on open highway. Fourteen young healthy men (mean age [±SD] = 23.4 [±1.7] years) participated Inappropriate line crossings (ILC) in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3–5am) driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05) for the intermediate (1–5am) driving session and by 4.0 (CI, 1.7 to 9.4; P<.001) for the long (9pm–5am) driving session. Compared to the reference session (9–10pm), the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001), 15.4 (CI, 4.6 to 51.5; P<.001) and 24.3 (CI, 7.4 to 79.5; P<.001), respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05) and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01). At night, extended driving impairs driving performances and therefore should be limited

Contribution à l'étude du cortex cingulaire antérieur dans la planification de l'action et l'adaptation comportementale (une approche électrophysiologique du rôle de l'aire 24c chez le primate)

BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocSudocFranceF

Analyse du rôle des processus moteurs, motivationnels et cognitifs dans l'akinésie (approches comportementale et neuroanatomique chez le rat traité par la 6-OHDA)

L'akinésie est l'un des symptômes caractéristiques de la maladie de Parkinson. Akinésie se traduit littéralement par absence de mouvement. L'existence de l'akinésie dans la schizophrénie et la dépression suppose un aspect psychomoteur. Par ailleurs, ces pathologies sont associées à un déséquilibre dopaminergique dans le système nerveux central. Nous avons émis l'hypothèse que le dysfonctionnement des différentes voies dopaminergiques pourrait être à l'origine de l'akinésie. Nous avons utilisé un modèle de lésion bilatérale partielle de la substance noire compacte (SNc) ou de l'aire tegmentale ventrale (ATV). L'approche neuroanatomique a permis de montrer que seule la lésion de l'ATV augmente le niveau d'expression des récepteurs D1 au niveau cortical. Nous avons étudié l'effet relatif de ces lésions sur des processus moteurs et cognitifs. Cette étude met en avant une différence entre un "syndrome nigral" (principalement moteur) et un "syndrome tegmental" (essentiellement cognitif).Akinesia is a principal feature of Parkinson's disease. The word akinesia literally means absence of movement. Akinetic symptom in depression and schizophrenia embodies the hypothesis that akinesia involves more than only motor behaviour. Moreover, these disorders have all been associated with evidence of dopamine disrupted homeostasis in the central nervous system. We intended to relate the respective involvement of the nigrostriatal and mesocortical pathways to akinesia. We used a partial bilateral lesioned model of the substania nigra pars compacta (SNc) or ventral tegmental area (VTA). Neuroanatomical study showed that only VTA lesions increased the level of D1 binding in cortical areas. In a second step, we studied the relative effect of lesions on motor and basic cognitive processing. This study highlighted the difference between a "nigral syndrome" (mainly motor) and a "tegmental syndrome" mainly cognitive).BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF