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In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other.

Mechanistic insights into visual hallucinations (VH) in Parkinson's disease (PD) have suggested a role for impaired attentional processes. The current study tested 25 PD patients with and 28 PD patients without VH on the attentional network test. Hallucinators had significantly lower accuracy rates compared to non-hallucinators, but no differences were found in reaction times. This suggests that hallucinators show deficits in attentional processes and conflict monitoring. Our findings provide novel behavioural insights that dovetail with current neurobiological frameworks of VH.

Background: Intrathecal morphine provides effective postoperative analgesia, but their use is associated with numerous side effects, including pruritus, nausea, vomiting, urinary retention, and respiratory depression. Pruritus is the most common side effect with a reported incidence of 58-85%., Objectives: This prospective, randomized, and double-blinded study was performed for women scheduled for cesarean delivery using spinal anesthesia to compare nalbuphine and ondansetron in the prevention of intrathecal morphine-induced pruritus., Patients and Methods: Ninety women after spinal anesthesia with hyperbaric bupivacaine and intrathecal morphine patients randomly divided into three groups. Women in placebo group (P group) received 4 ml of normal saline intravenous (IV) injection, nalbuphine group (N group) received 4 ml of a 4 mg nalbuphine IV injection, and ondansetron 4 group (O group) received 4 ml of a 4 mg ondansetron IV injection, immediately after delivery of the baby. Studied women observed in postanesthesia care unit for 4 h. The primary outcome measures success of the treatment, defined as a pruritus score 1 (no pruritus) or 2 (mild pruritus - no treatment required) at 20 min after treatment., Results: Although, three was no significant difference between the three studied groups regarding; score 1 pruritus, while, score 2 pruritus (mild pruritus - no treatment requested) was significantly high in N and O groups compared to placebo group. Pruritus score 1 (no pruritus) plus pruritus score 2 were significantly high in N and O groups compared to placebo group (20 cases, 20 cases, 5 cases; respectively, P = 0.008). In addition; score 3 pruritus (moderate - treatment requested) was significantly less in N and O groups compared to placebo group., Conclusion: Nalbuphine and ondansetron were found to be more effective than placebo for prevention of intrathecal morphine-induced pruritus in women undergoing cesarean delivery and nalbuphine is preferred than ondansetron because it is not excreted in the breast milk.

Objective: Evidence is accumulating that childhood trauma might be associated with higher severity of positive symptoms in patients with psychosis and higher incidence of psychotic experiences in non-clinical populations. However, it remains unknown whether the history of childhood trauma might be associated with particular types of auditory verbal hallucinations (AVH)., Method: We assessed childhood trauma using the Early Trauma Inventory Self-Report - Short Form (ETISR-SF) in 94 first-episode schizophrenia (FES) patients. Lifetime psychopathology was evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist, while symptoms on the day of assessment were examined using the Positive and Negative Syndrome Scale (PANSS). Based on ETISR-SF, patients were divided into those with and without the history of childhood trauma: FES(+) and FES(-) patients., Results: FES(+) patients had significantly higher total number of AVH types and Schneiderian first-rank AVH as well as significantly higher PANSS P3 item score (hallucinatory behavior) in comparison with FES(-) patients. They experienced significantly more frequently third person AVH and abusive/accusatory/persecutory voices. These differences remained significant after controlling for education, PANSS depression factor score and chlorpromazine equivalent. Linear regression analysis revealed that the total number of AVH types was predicted by sexual abuse score after controlling for above mentioned confounders. This effect was significant only in females., Conclusion: Our results indicate that the history of childhood trauma, especially sexual abuse, is associated with higher number AVH in females but not in males. Third person AVH and abusive/accusatory/persecutory voices, representing Schneiderian first-rank symptoms, might be particularly related to childhood traumatic events., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Dopamine neurons are sensitive to novel and rewarding events, and dopamine signals can modulate learning in higher-level brain networks. Additionally, dopamine abnormalities appear to be central to the pathophysiology of schizophrenia spectrum disorders. In this study, we investigate the dopaminergic modulation of schizotypal traits and exploration after expectancy violations in Parkinson's disease (PD) patients on dopamine replacement therapy. Exploration after expectancy violations was measured with a latent inhibition and an anomaly categorisation task. Patients with PD had significantly elevated levels of schizotypy and reduced latent inhibition, relative to the controls. Anomaly categorisation was enhanced at trend level among the patients. Dopaminergic antiparkinsonian drugs showed dose-dependent effects: they induced psychotic-like experiences, and at the same time, they disrupted latent inhibition and made categorisation of anomaly more efficient. Most of these findings were replicated in an independent sample of patients with PD. An up-regulated dopamine system in medicated PD patients might tune higher-level brain networks to engage in learning when faced with unexpected information, and therefore hasten the updating of internal models., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects., Method: Adults meeting DSM-IV criteria for heroin dependence and treated with opioid medication (n = 27) and healthy controls (n = 26) were recruited between March 2013 and October 2013 and given a computer-based task to assess avoidance behavior. For this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship or hide in safe areas to avoid on-screen aversive events. Hiding duration during different periods of the task was used to measure avoidance behavior., Results: While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent men (but not women) made more avoidance responses during a warning signal that predicted the aversive event (analysis of variance, sex × group interaction, P = .007). Heroin-dependent men were also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (P = .011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that, in male patients, differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity., Conclusions: This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest that abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction and may facilitate development of therapeutic approaches to help affected individuals., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objective: To investigate the effects of pioglitazone on pelvic ganglion neurons in a rat model of bilateral cavernosal nerve crush injury (BCNI), thereby elucidating the actions of pioglitazone in preventing post-prostatectomy neurogenic erectile dysfunction., Methods: Sprague-Dawley rats aged 12 weeks were divided into four groups: (a) sham procedure, (b) BCNI, (c) BCNI + postsurgical pioglitazone, and (d) BCNI + pre and postsurgical pioglitazone (preventive therapy). Preoperative injection of Fluoro-Gold (FG) fluorescent tracer into the cavernosal tissue was performed for retrograde labeling of pelvic ganglion cells. Pelvic ganglia were resected at 2 weeks in all rats and processed for real-time polymerase chain reaction, immunohistochemistry, and Western blot to examine the expression of FG, neuronal nitric oxide synthase, β-III tubulin, neurturin, and glial cell line-derived neurotrophic factor family receptor alpha-2 (GFRα2)., Results: Animals treated with pre- and postsurgical pioglitazone demonstrated increased staining for FG similar to sham levels. Gene expression of neuronal nitric oxide synthase, neurturin, GFRα2, and β-III tubulin was also upregulated in the group receiving preventive therapy., Conclusion: Pioglitazone provides a protective effect on pelvic ganglion neurons after BCNI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for differentiating lung adenocarcinoma from squamous cell carcinoma and also for differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair-boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic carcinomas and help to determine the primary sites of metastatic carcinomas. Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively. While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %, respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of papillary carcinoma respectively, and both were positive in 100 % of follicular carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8 were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 % of chromophobe carcinoma respectively. TTF-1 was negative in all renal carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of serous mucinous carcinomas, respectively. It was also positive in 100 % of endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF-1, and PAX8 may help in differentiating between primary lung adenocarcinoma and metastatic lung carcinomas.

Pharmacological studies implicate the blockade of adenosine receptorsas an effective strategy for reducing Parkinson's disease (PD) symptoms. The objective of this study is to elucidate the possible protective effects of ZM241385 and 8-cyclopentyl-1, 3-dipropylxanthine, two selective A2A and A1 receptor antagonists, on a rotenone rat model of PD. Rats were split into four groups: vehicle control (1 ml/kg/48 h), rotenone (1.5 mg/kg/48 h, s.c.), ZM241385 (3.3 mg/kg/day, i.p) and 8-cyclopentyl-1, 3-dipropylxanthine (5 mg/kg/day, i.p). After that, animals were subjected to behavioral (stride length and grid walking) and biochemical (measuring concentration of dopamine levels using high performance liquid chromatography, HPLC). In the rotenone group, rats displayed a reduced motor activity and disturbed movement coordination in the behavioral tests and a decreased dopamine concentration as foundby HPLC. The effect of rotenone was partially prevented in the ZM241385 group, but not with 8-cyclopentyl-1,3-dipropylxanthine administration. The administration of ZM241385 improved motor function and movement coordination (partial increase of stride length and partial decrease in the number of foot slips) and an increase in dopamine concentration in the rotenone-injected rats. However, the 8-cyclopentyl-1,3-dipropylxanthine and rotenone groups were not significantly different. These results indicate that selective A2A receptor blockade by ZM241385, but not A1 receptor blockadeby 8-cyclopentyl-1,3-dipropylxanthine, may treat PD motor symptoms. This reinforces the potential use of A2A receptor antagonists as a treatment strategy for PD patients.

Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder (MDD), Parkinson's disease (PD), schizophrenia, posttraumatic stress disorder (PTSD) and Alzheimer's disease (AD). In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders.

A novel approach for the resolution and quantitation of severely overlapped quaternary mixture of carbinoxamine maleate (CAR), pholcodine (PHL), ephedrine hydrochloride (EPH) and sunset yellow (SUN) in syrup was demonstrated utilizing different spectrophotometric assisted multivariate calibration methods. The applied methods have used different processing and pre-processing algorithms. The proposed methods were partial least squares (PLS), concentration residuals augmented classical least squares (CRACLS), and a novel method; continuous wavelet transforms coupled with partial least squares (CWT-PLS). These methods were applied to a training set in the concentration ranges of 40-100 μg/mL, 40-160 μg/mL, 100-500 μg/mL and 8-24 μg/mL for the four components, respectively. The utilized methods have not required any preliminary separation step or chemical pretreatment. The validity of the methods was evaluated by an external validation set. The selectivity of the developed methods was demonstrated by analyzing the drugs in their combined pharmaceutical formulation without any interference from additives. The obtained results were statistically compared with the official and reported methods where no significant difference was observed regarding both accuracy and precision., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals' performance on the task. Although behavioral results showed that opioid-addicted individuals performed as well as controls on both reward- and punishment-based learning, the modeling results suggested subtle differences in how decisions were made between the two groups. Specifically, the opioid-addicted group showed decreased tendency to repeat prior responses, meaning that they were more likely to "chase reward" when expectancies were violated, whereas controls were more likely to stick with a previously-successful response rule, despite occasional expectancy violations. This tendency to chase short-term reward, potentially at the expense of developing rules that maximize reward over the long term, may be a contributing factor to opioid addiction. Further work is indicated to better understand whether this tendency arises as a result of brain changes in the wake of continued opioid use/abuse, or might be a pre-existing factor that may contribute to risk for addiction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Avoidance behavior is a critical component of many psychiatric disorders, and as such, it is important to understand how avoidance behavior arises, and whether it can be modified. In this study, we used empirical and computational methods to assess the role of informational feedback and ambiguous outcome in avoidance behavior. We adapted a computer-based probabilistic classification learning task, which includes positive, negative and no-feedback outcomes; the latter outcome is ambiguous as it might signal either a successful outcome (missed punishment) or a failure (missed reward). Prior work with this task suggested that most healthy subjects viewed the no-feedback outcome as strongly positive. Interestingly, in a later version of the classification task, when healthy subjects were allowed to opt out of (i.e. avoid) responding, some subjects ("avoiders") reliably avoided trials where there was a risk of punishment, but other subjects ("non-avoiders") never made any avoidance responses at all. One possible interpretation is that the "non-avoiders" valued the no-feedback outcome so positively on punishment-based trials that they had little incentive to avoid. Another possible interpretation is that the outcome of an avoided trial is unspecified and that lack of information is aversive, decreasing subjects' tendency to avoid. To examine these ideas, we here tested healthy young adults on versions of the task where avoidance responses either did or did not generate informational feedback about the optimal response. Results showed that provision of informational feedback decreased avoidance responses and also decreased categorization performance, without significantly affecting the percentage of subjects classified as "avoiders." To better understand these results, we used a modified Q-learning model to fit individual subject data. Simulation results suggest that subjects in the feedback condition adjusted their behavior faster following better-than-expected outcomes, compared to subjects in the no-feedback condition. Additionally, in both task conditions, "avoiders" adjusted their behavior faster following worse-than-expected outcomes, and treated the ambiguous no-feedback outcome as less rewarding, compared to non-avoiders. Together, results shed light on the important role of ambiguous and informative feedback in avoidance behavior.

In a series of 1-shot economic trust games in which participants could make real monetary profits, but also risked losing money, 2 studies compared young and older adults' trust (amount invested with trustees) and trustworthiness (amount returned to investors by trustees). In Study 1, young (n = 35) and older (n = 32) participants acted as investors, and the age of simulated trustees (young, older) was manipulated. In Study 2, young (n = 61) and older (n = 67) participants acted in real life as both investors and trustees. They completed 2 face-to-face trust games with same- and other-age partners, and 3 anonymous trust games with same-, other-, and unknown-age partners. Study 1 found that young and older participants rate older trustees as appearing more trustworthy than young trustees, but neither group invest more with older than young trustees. Rather, older participants were more likely than young participants to invest money averaged across trustee age. In Study 2, there were no age-related differences in trust, but older adults were more trustworthy than young adults in anonymous games with same- and unknown-age partners. It was also found that young adults demonstrate greater reputational concerns than older adults by reciprocating more trust when face-to-face than anonymous. We discuss the complex influences of age on trust game investing and reciprocation, as well as the implications for older adults' wellbeing and financial security., ((c) 2015 APA, all rights reserved).)

In this study, we tested reward- and punishment learning performance using a probabilistic classification learning task in patients with schizophrenia (n=37) and healthy controls (n=48). We also fit subjects' data using a Drift Diffusion Model (DDM) of simple decisions to investigate which components of the decision process differ between patients and controls. Modeling results show between-group differences in multiple components of the decision process. Specifically, patients had slower motor/encoding time, higher response caution (favoring accuracy over speed), and a deficit in classification learning for punishment, but not reward, trials. The results suggest that patients with schizophrenia adopt a compensatory strategy of favoring accuracy over speed to improve performance, yet still show signs of a deficit in learning based on negative feedback. Our data highlights the importance of applying fitting models (particularly drift diffusion models) to behavioral data. The implications of these findings are discussed relative to theories of schizophrenia and cognitive processing., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Previous 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. In Experiment 1, the first group of subjects received an intermixed task in which reward and punishment trials were presented in the same block, as a standard baseline task. In Experiment 2, a second group completed the separated task, in which reward and punishment trials were presented in separate blocks. Additionally, in order to understand the mechanisms underlying performance in the experimental conditions, we fit individual data using a Q-learning model. Results from Experiment 1 show that subjects who completed the intermixed task paradoxically valued the no-feedback outcome as a reinforcer when it occurred on reinforcement-based trials, and as a punisher when it occurred on punishment-based trials. This is supported by patterns of empirical responding, where subjects showed more win-stay behavior following an explicit reward than following an omission of punishment, and more lose-shift behavior following an explicit punisher than following an omission of reward. In Experiment 2, results showed similar performance whether subjects received reward-based or punishment-based trials first. However, when the Q-learning model was applied to these data, there were differences between subjects in the reward-first and punishment-first conditions on the relative weighting of neutral feedback. Specifically, early training on reward-based trials led to omission of reward being treated as similar to punishment, but prior training on punishment-based trials led to omission of reward being treated more neutrally. This suggests that early training on one type of trials, specifically reward-based trials, can create a bias in how neutral feedback is processed, relative to those receiving early punishment-based training or training that mixes positive and negative outcomes.

There is significant evidence that in addition to reward-punishment based decision making, the Basal Ganglia (BG) contributes to risk-based decision making (Balasubramani et al., 2014). Despite this evidence, little is known about the computational principles and neural correlates of risk computation in this subcortical system. We have previously proposed a reinforcement learning (RL)-based model of the BG that simulates the interactions between dopamine (DA) and serotonin (5HT) in a diverse set of experimental studies including reward, punishment and risk based decision making (Balasubramani et al., 2014). Starting with the classical idea that the activity of mesencephalic DA represents reward prediction error, the model posits that serotoninergic activity in the striatum controls risk-prediction error. Our prior model of the BG was an abstract model that did not incorporate anatomical and cellular-level data. In this work, we expand the earlier model into a detailed network model of the BG and demonstrate the joint contributions of DA-5HT in risk and reward-punishment sensitivity. At the core of the proposed network model is the following insight regarding cellular correlates of value and risk computation. Just as DA D1 receptor (D1R) expressing medium spiny neurons (MSNs) of the striatum were thought to be the neural substrates for value computation, we propose that DA D1R and D2R co-expressing MSNs are capable of computing risk. Though the existence of MSNs that co-express D1R and D2R are reported by various experimental studies, prior existing computational models did not include them. Ours is the first model that accounts for the computational possibilities of these co-expressing D1R-D2R MSNs, and describes how DA and 5HT mediate activity in these classes of neurons (D1R-, D2R-, D1R-D2R- MSNs). Starting from the assumption that 5HT modulates all MSNs, our study predicts significant modulatory effects of 5HT on D2R and co-expressing D1R-D2R MSNs which in turn explains the multifarious functions of 5HT in the BG. The experiments simulated in the present study relates 5HT to risk sensitivity and reward-punishment learning. Furthermore, our model is shown to capture reward-punishment and risk based decision making impairment in Parkinson's Disease (PD). The model predicts that optimizing 5HT levels along with DA medications might be essential for improving the patients' reward-punishment learning deficits.

Impulsivity, i.e. irresistibility in the execution of actions, may be prominent in Parkinson's disease (PD) patients who are treated with dopamine precursors or dopamine receptor agonists. In this study, we combine clinical investigations with computational modeling to explore whether impulsivity in PD patients on medication may arise as a result of abnormalities in risk, reward and punishment learning. In order to empirically assess learning outcomes involving risk, reward and punishment, four subject groups were examined: healthy controls, ON medication PD patients with impulse control disorder (PD-ON ICD) or without ICD (PD-ON non-ICD), and OFF medication PD patients (PD-OFF). A neural network model of the Basal Ganglia (BG) that has the capacity to predict the dysfunction of both the dopaminergic (DA) and the serotonergic (5HT) neuromodulator systems was developed and used to facilitate the interpretation of experimental results. In the model, the BG action selection dynamics were mimicked using a utility function based decision making framework, with DA controlling reward prediction and 5HT controlling punishment and risk predictions. The striatal model included three pools of Medium Spiny Neurons (MSNs), with D1 receptor (R) alone, D2R alone and co-expressing D1R-D2R. Empirical studies showed that reward optimality was increased in PD-ON ICD patients while punishment optimality was increased in PD-OFF patients. Empirical studies also revealed that PD-ON ICD subjects had lower reaction times (RT) compared to that of the PD-ON non-ICD patients. Computational modeling suggested that PD-OFF patients have higher punishment sensitivity, while healthy controls showed comparatively higher risk sensitivity. A significant decrease in sensitivity to punishment and risk was crucial for explaining behavioral changes observed in PD-ON ICD patients. Our results highlight the power of computational modelling for identifying neuronal circuitry implicated in learning, and its impairment in PD. The results presented here not only show that computational modelling can be used as a valuable tool for understanding and interpreting clinical data, but they also show that computational modeling has the potential to become an invaluable tool to predict the onset of behavioral changes during disease progression.

To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either "explore" or "exploit" or "not to take any action" for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior.

The cerebellum has been considered for a long time to play a role solely in motor coordination. However, studies over the past two decades have shown that the cerebellum also plays a key role in many motor, cognitive, and emotional processes. In addition, studies have also shown that the cerebellum is implicated in many psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders. In this review, we discuss existing studies reporting cerebellar dysfunction in various psychiatric disorders. We will also discuss future directions for studies linking the cerebellum to psychiatric disorders.

Synapses act as information filters by different molecular mechanisms including retrograde messenger that affect neuronal spiking activity. One of the well-known effects of retrograde messenger in presynaptic neurons is a change of the probability of neurotransmitter release. Hebbian learning describe a strengthening of a synapse between a presynaptic input onto a postsynaptic neuron when both pre- and postsynaptic neurons are coactive. In this work, a theory of homeostatic regulation of neurotransmitter release by retrograde messenger and Hebbian plasticity in neuronal encoding is presented. Encoding efficiency was measured for different synaptic conditions. In order to gain high encoding efficiency, the spiking pattern of a neuron should be dependent on the intensity of the input and show low levels of noise. In this work, we represent spiking trains as zeros and ones (corresponding to non-spike or spike in a time bin, respectively) as words with length equal to three. Then the frequency of each word (here eight words) is measured using spiking trains. These frequencies are used to measure neuronal efficiency in different conditions and for different parameter values. Results show that neurons that have synapses acting as band-pass filters show the highest efficiency to encode their input when both Hebbian mechanism and homeostatic regulation of neurotransmitter release exist in synapses. Specifically, the integration of homeostatic regulation of feedback inhibition with Hebbian mechanism and homeostatic regulation of neurotransmitter release in the synapses leads to even higher efficiency when high stimulus intensity is presented to the neurons. However, neurons with synapses acting as high-pass filters show no remarkable increase in encoding efficiency for all simulated synaptic plasticity mechanisms. This study demonstrates the importance of cooperation of Hebbian mechanism with regulation of neurotransmitter release induced by rapid diffused retrograde messenger in neurons with synapses as low and band-pass filters to obtain high encoding efficiency in different environmental and physiological conditions.

Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during "non-threat" periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Information processing in the hippocampus begins by transferring spiking activity of the entorhinal cortex (EC) into the dentate gyrus (DG). Activity pattern in the EC is separated by the DG such that it plays an important role in hippocampal functions including memory. The structural and physiological parameters of these neural networks enable the hippocampus to be efficient in encoding a large number of inputs that animals receive and process in their life time. The neural encoding capacity of the DG depends on its single neurons encoding and pattern separation efficiency. In this study, encoding by the DG is modeled such that single neurons and pattern separation efficiency are measured using simulations of different parameter values. For this purpose, a probabilistic model of single neurons efficiency is presented to study the role of structural and physiological parameters. Known neurons number of the EC and the DG is used to construct a neural network by electrophysiological features of granule cells of the DG. Separated inputs as activated neurons in the EC with different firing probabilities are presented into the DG. For different connectivity rates between the EC and DG, pattern separation efficiency of the DG is measured. The results show that in the absence of feedback inhibition on the DG neurons, the DG demonstrates low separation efficiency and high firing frequency. Feedback inhibition can increase separation efficiency while resulting in very low single neuron's encoding efficiency in the DG and very low firing frequency of neurons in the DG (sparse spiking). This work presents a mechanistic explanation for experimental observations in the hippocampus, in combination with theoretical measures. Moreover, the model predicts a critical role for impaired inhibitory neurons in schizophrenia where deficiency in pattern separation of the DG has been observed.

Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Propantheline bromide (PB) is a hydrolysable anti-cholinergic drug. A novel strategy for the online monitoring of PB degradation kinetics catalysed by hydroxyl ions is presented. This is achieved by the incorporation of an on-site PB-selective electrode constructed using as an ionophore. This sensor was used to track the hydrolysis of PB by continuous measurement of the decrease in the produced emf over time. The use of this new technique provides real-time observation and yields a continuous profile of the hydrolysis behaviour of PB under various pH conditions as well as the temperature dependency of each reaction. Moreover, a great advantage of this proposed on-line system is its higher accuracy for rate constant estimation relative to other off-line methods. This kinetic data analysis permitted the determination of the hydrolysis activation energy and prediction of the drug shelf life. The estimated activation energy from Arrhenius plot was 20.77 kcal mol(-1)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Comparisons of cognitive impairments between schizophrenia (SZ) and bipolar disorder (BPD) have produced mixed results. We applied different working memory (WM) measures (Digit Span Forward and Backward, Short-delay and Long-delay CPT-AX, N-back) to patients with SZ (n = 23), psychotic BPD (n = 19) and non-psychotic BPD (n = 24), as well as to healthy controls (HC) (n = 18) in order to compare the level of WM impairments across the groups. With respect to the less demanding WM measures (Digit Span Forward and Backward, Short-delay CPT-AX), there were no between group differences in cognitive performance; however, with respect to the more demanding WM measures (Long-delay CPT-AX, N-back), we observed that the groups with psychosis (SZ, psychotic BPD) did not differ from one another, but performed poorer than the group without a history of psychosis (non-psychotic BPD). A history of psychotic symptoms may influence cognitive performance with respect to WM delay and load effects as measured by Long-delay CPT-AX and N-back tests, respectively. We observed a positive correlation of WM performance with antipsychotic treatment and a negative correlation with depressive symptoms in BPD and with negative symptoms in SZ subgroup. Our study suggests that WM dysfunctions are more closely related to a history of psychosis than to the diagnostic categories of SZ and BPD described by psychiatric classification systems.

Objectives: The purpose of this study was to assess the role of transperineal sonography in assessment of pathologic changes to the anal sphincter complex in patients with chronic anal fissures., Methods: We conducted a prospective case-control study of 100 consecutive patients of any age and both sexes with chronic anal fissures who presented to a colorectal clinic between January 2012 and August 2013 (group A) and 50 healthy volunteers (group B)., Results: The most common patterns of radiologic changes to anal sphincters associated with chronic anal fissures were circumferential thickening of the anal sphincter complex in 5 patients (5%), circumferential thickening of the internal anal sphincter in 3 patients (3%), preferential thickening of the internal anal sphincter at the 6-o'clock position in 80 patients (80%) and the 12-o'clock position in 7 patients (7%), preferential thickening of the internal and external anal sphincters in 3 patients (3%), and thinning of the internal anal sphincter in 2 patients (2%)., Conclusions: Chronic anal fissures cause differential thickening of both internal and external anal sphincters, with a trend toward increased thickness in relation to the site of the fissure. Routine preoperative transperineal sonography for patients with chronic anal fissures is recommended, and it is mandatory in high-risk patients., (© 2014 by the American Institute of Ultrasound in Medicine.)

The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives.

Background: Prior studies report that monoamine oxidases inhibitors (MAO-I) when used as an adjunct to levodopa ameliorate motor symptoms in Parkinson's disease (PD), but this was not tested in relation to cognitive or psychiatric measures., Objective: Here, we tested the effects of MAO-I as an adjunct to levodopa, in comparison to levodopa or dopamine (DA) agonists alone, on various cognitive, affective and quality of life measures., Methods: We studied three groups of subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD patients on levodopa or DA agonists only., Results: We found that compared to monotherapy, combined MAO-I and levodopa seemed to improve cognition, including probabilistic learning, working memory and executive functions. There were no differences between the different medication regimes on deterministic learning, attention or memory recall. It was also found that MAO-I as an adjunct to levodopa improves affective measures such as depression, apathy, anxiety and quality of life. Interestingly, this enhancing effect of combined levodopa and MAO-I was more pronounced in PD patients with severe akinesia, compared to patients with severe tremor., Conclusion: Our data are in agreement with (a) the Continuous Dopaminergic Stimulation (CDS) theory which states that continuous stimulation of the basal ganglia enhances motor, psychiatric and cognitive functions in PD patients; and/or (b) findings that MAO-I increase the bioavailability of monoamines that have beneficial effects on motor and behavioral dysfunction in PD.

A substantial subset of Parkinson's disease (PD) patients suffers from impulse control disorders (ICDs), which are side effects of dopaminergic medication. Dopamine plays a key role in reinforcement learning processes. One class of reinforcement learning models, known as the actor-critic model, suggests that two components are involved in these reinforcement learning processes: a critic, which estimates values of stimuli and calculates prediction errors, and an actor, which estimates values of potential actions. To understand the information processing mechanism underlying impulsive behavior, we investigated stimulus and action value learning from reward and punishment in four groups of participants: on-medication PD patients with ICD, on-medication PD patients without ICD, off-medication PD patients without ICD, and healthy controls. Analysis of responses suggested that participants used an actor-critic learning strategy and computed prediction errors based on stimulus values rather than action values. Quantitative model fits also revealed that an actor-critic model of the basal ganglia with different learning rates for positive and negative prediction errors best matched the choice data. Moreover, whereas ICDs were associated with model parameters related to stimulus valuation (critic), PD was associated with parameters related to action valuation (actor). Specifically, PD patients with ICD exhibited lower learning from negative prediction errors in the critic, resulting in an underestimation of adverse consequences associated with stimuli. These findings offer a specific neurocomputational account of the nature of compulsive behaviors induced by dopaminergic drugs., (Copyright © 2014 the authors 0270-6474/14/347814-11$15.00/0.)

Four, accurate, precise, and sensitive spectrophotometric methods are developed for the simultaneous determination of a ternary mixture containing amlodipine besylate (AM), olmesartan medoxomil (OL) and hydrochlorothiazide (HZ), where AM is determined at its λ(max) 364.6 nm ((0)D), while (OL) and (HZ) are determined by different methods. Method (A) depends on determining OL and HZ by measuring the second derivative of the ratio spectra ((2)DD) at 254.4 and 338.6 nm, respectively. Method (B) is first derivative of the double divisor ratio spectra (D-(1)DD) at 260.4 and 273.0 nm for OL and HZ, respectively. Method (C) based on successive spectrophotometric resolution technique (SSRT). The technique starts with the ratio subtraction method then measuring OL and HZ at their isoabsorptive point at 260.0 nm, while HZ is measured using the amplitude of first derivative at 335.2 nm. Method (D) is mean centering of the ratio spectra (MCR) at 252.0 nm and 220.0 nm for OL and HZ, respectively. The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures containing different ratios of the three drugs and their combined dosage form. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p=0.05., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Although empirical and neural studies show that serotonin (5HT) plays many functional roles in the brain, prior computational models mostly focus on its role in behavioral inhibition. In this study, we present a model of risk based decision making in a modified Reinforcement Learning (RL)-framework. The model depicts the roles of dopamine (DA) and serotonin (5HT) in Basal Ganglia (BG). In this model, the DA signal is represented by the temporal difference error (δ), while the 5HT signal is represented by a parameter (α) that controls risk prediction error. This formulation that accommodates both 5HT and DA reconciles some of the diverse roles of 5HT particularly in connection with the BG system. We apply the model to different experimental paradigms used to study the role of 5HT: (1) Risk-sensitive decision making, where 5HT controls risk assessment, (2) Temporal reward prediction, where 5HT controls time-scale of reward prediction, and (3) Reward/Punishment sensitivity, in which the punishment prediction error depends on 5HT levels. Thus the proposed integrated RL model reconciles several existing theories of 5HT and DA in the BG.

We present a computational model of altered gait velocity patterns in Parkinson's Disease (PD) patients. PD gait is characterized by short shuffling steps, reduced walking speed, increased double support time and sometimes increased cadence. The most debilitating symptom of PD gait is the context dependent cessation in gait known as freezing of gait (FOG). Cowie et al. (2010) and Almeida and Lebold (2010) investigated FOG as the changes in velocity profiles of PD gait, as patients walked through a doorway with variable width. The former reported a sharp dip in velocity, a short distance from the doorway that was greater for narrower doorways. They compared the gait performance in PD freezers at ON and OFF dopaminergic medication. In keeping with this finding, the latter also reported the same for ON medicated PD freezers and non-freezers. In the current study, we sought to simulate these gait changes using a computational model of Basal Ganglia based on Reinforcement Learning, coupled with a spinal rhythm mimicking central pattern generator (CPG) model. In the model, a simulated agent was trained to learn a value profile over a corridor leading to the doorway by repeatedly attempting to pass through the doorway. Temporal difference error in value, associated with dopamine signal, was appropriately constrained in order to reflect the dopamine-deficient conditions of PD. Simulated gait under PD conditions exhibited a sharp dip in velocity close to the doorway, with PD OFF freezers showing the largest decrease in velocity compared to PD ON freezers and controls. PD ON and PD OFF freezers both showed sensitivity to the doorway width, with narrow door producing the least velocity/ stride length. Step length variations were also captured with PD freezers producing smaller steps and larger step-variability than PD non-freezers and controls. In addition this model is the first to explain the non-dopamine dependence for FOG giving rise to several other possibilities for its etiology.

Reinforcement learning (RL) models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still no theoretical consensus about what kind of time representation is used by the basal ganglia. We review several theoretical accounts and their supporting evidence. We then discuss the relationship between RL models and the timing mechanisms that have been attributed to the basal ganglia. We hypothesize that a single computational system may underlie both RL and interval timing-the perception of duration in the range of seconds to hours. This hypothesis, which extends earlier models by incorporating a time-sensitive action selection mechanism, may have important implications for understanding disorders like Parkinson's disease in which both decision making and timing are impaired.

Introduction: Psychosis and hallucinations occur in 20-30% of patients with Parkinson's disease (PD). In the current study, we investigate cognitive functions in relation to the occurrence of psychosis in PD patients., Methods: We tested three groups of subjects - PD with psychosis, PD without psychosis and healthy controls - on working memory, learning and transitive inference tasks, which are known to assess prefrontal, basal ganglia and hippocampal functions., Results: In the working memory task, results show that patients with and without psychosis were more impaired than the healthy control group. In the transitive inference task, we did not find any difference among the groups in the learning phase performance. Importantly, PD patients with psychosis were more impaired than both PD patients without psychosis and controls at transitive inference. We also found that the severity of psychotic symptoms in PD patients [as measured by the Unified Parkinson Disease Rating Scale Thought Disorder (UPDRS TD) item] is directly associated with the severity of cognitive impairment [as measured by the mini-mental status exam (MMSE)], sleep disturbance [as measured by the Scales for Outcome in Parkinson Disease (SCOPA) sleep scale] and transitive inference (although the latter did not reach significance)., Conclusions: Although hypothetical, our data may suggest that the hippocampus is a neural substrate underlying the occurrence of psychosis, sleep disturbance and cognitive impairment in PD patients.

Five simple and sensitive methods were developed for the determination of tofisopam (TF). The first four are stability-indicating depending on the determination of TF in the presence of its degradation product, while the fifth depended on the determination of TF via its degradation product. Method A was based on first and second derivative spectrophotometry, D and 2D, measuring the amplitude at 298 and 332 nm in the case of 1D and at 312 and 344 nm in the case of 2D. Method B depended on measuring the peak amplitude of the first derivative of the ratio spectra 1DD at 336 nm. Method C was based on difference spectrophotometry by measuring deltaA at 366 nm. Method D was a TLC method using silica gel 60 F254 plates, the optimized mobile phase ethyl acetate-methanol-ammonium hydroxide 10% (8.5 + 1.0 + 0.5, v/v/v), and quantification by densitometric scanning at 315 nm. In method E, spectrofluorometry was applied for the determination of TF via its degradation product; maximum emission was 383 nm when excitation was 295 nm. Linearities were obtained in the concentration range 2-20 microg/mL for methods A, B, and C and 2-20 microg/band and 0.2-1.6 microg/mL for D and E, respectively. In method A, the mean recoveries were 99.45 +/- 0.287 and 100.28 +/- 0.277% at 298 and 332 nm, respectively, in the case of 1D and 99.40 +/- 0.245% and 99.50 +/- 0.292% at 312 and 344 nm, respectively in the case of 2D. The mean recovery was 100.03 +/- 0.523% at 366 nm in method B. Method C showed mean recovery of 100.20 +/- 0.642%. Recoveries for methods D and E were 98.98 +/- 0.721 and 100.25 +/- 0.282%, respectively. The degradation product was obtained in acidic stress condition, separated, and identified by IR and mass spectral analysis, from which the degradation product was confirmed and the degradation pathway was suggested. The first four methods were specific for TF in the presence of different concentrations of its degradation product. The five proposed methods were successfully applied for the determination of TF in Nodeprine tablets. Statistical comparison among the results obtained by these methods and that obtained by the official method for the determination of the drug was made, and no significant differences were found.

Parkinson's disease (PD) is a neurological disorder, associated with rigidity, bradykinesia, and resting tremor, among other motor symptoms. In addition, patients with PD also show cognitive and psychiatric dysfunction, including dementia, mild cognitive impairment (MCI), depression, hallucinations, among others. Interestingly, the occurrence of these symptoms-motor, cognitive, and psychiatric-vary among individuals, such that a subgroup of PD patients might show some of the symptoms, but another subgroup does not. This has prompted neurologists and scientists to subtype PD patients depending on the severity of symptoms they show. Neural studies have also mapped different motor, cognitive, and psychiatric symptoms in PD to different brain networks. In this review, we discuss the neural and behavioral substrates of most common subtypes of PD patients, that are related to the occurrence of: (a) resting tremor (vs. nontremor-dominant); (b) MCI; (c) dementia; (d) impulse control disorders (ICD); (e) depression; and/or (f) hallucinations. We end by discussing the relationship among subtypes of PD subgroups, and the relationship among motor, cognitive, psychiatric factors in PD.

Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in PD does not account for the possible contribution of other pathological changes that occur in the disease process, importantly including gray matter loss. To address this gap in the literature, the current study explored the relationship between fronto-striatal gray matter atrophy and learning in PD. We employed a discrimination learning task and computational modeling in order to assess learning rates in non-demented PD patients. Behaviorally, we confirmed that learning rates were reduced in patients relative to controls. Furthermore, voxel-based morphometry imaging analysis demonstrated that this learning impairment was directly related to gray matter loss in discrete fronto-striatal regions (specifically, the ventromedial prefrontal cortex, inferior frontal gyrus and nucleus accumbens). These findings suggest that dopaminergic imbalance may not be the sole determinant of discrimination learning deficits in PD, and highlight the importance of factoring in the broader pathological changes when constructing models of learning in PD.

Many computational models of the basal ganglia (BG) have been proposed over the past twenty-five years. While computational neuroscience models have focused on closely matching the neurobiology of the BG, computational cognitive neuroscience (CCN) models have focused on how the BG can be used to implement cognitive and motor functions. This review article focuses on CCN models of the BG and how they use the neuroanatomy of the BG to account for cognitive and motor functions such as categorization, instrumental conditioning, probabilistic learning, working memory, sequence learning, automaticity, reaching, handwriting, and eye saccades. A total of 19 BG models accounting for one or more of these functions are reviewed and compared. The review concludes with a discussion of the limitations of existing CCN models of the BG and prescriptions for future modeling, including the need for computational models of the BG that can simultaneously account for cognitive and motor functions, and the need for a more complete specification of the role of the BG in behavioral functions.