A model study on the circuit mechanism underlying decision-making in Drosophila

Previous elegant experiments in a flight simulator showed that conditioned Drosophila is able to make a clear-cut decision to avoid potential danger. When confronted with conflicting visual cues, the relative saliency of two competing cues is found to be a sensory ruler for flies to judge which cue should be used for decision-making. Further genetic manipulations and immunohistological analysis revealed that the dopamine system and mushroom bodies are indispensable for such a clear-cut or nonlinear decision. The neural circuit mechanism, however, is far from being clear. In this paper, we adopt a computational modeling approach to investigate how different brain areas and the dopamine system work together to drive a fly to make a decision. By developing a systems-level neural network, a two-pathway circuit is proposed. Besides a direct pathway from a feature binding area to the motor center, another connects two areas via the mushroom body, a target of dopamine release. A raised dopamine level is hypothesized to be induced by complex choice tasks and to enhance lateral inhibition and steepen the units’ response gain in the mushroom body. Simulations show that training helps to assign values to formerly neutral features. For a circuit model with a blocked mushroom body, the direct pathway passes all alternatives to the motor center without changing original values, giving rise to a simple choice characterized by a linear choice curve. With respect to an intact circuit, enhanced lateral inhibition dependent on dopamine critically promotes competition between alternatives, turning the linear- into nonlinear choice behavior. Results account well for experimental data, supporting the reasonableness of model working hypotheses. Several testable predictions are made for future studies.     

Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine.

The relationship between a rat's locomotor response to a novel environment and its behavioral and dopaminergic responses to cocaine was examined. Subjects were divided into two groups based on their locomotor response to a novel environment. Subjects who had a novelty response above the median were classified as high responders (HR), while those with a novelty response below the median were classified as low responders (LR). Following administration of cocaine-HCl (0, 2.5, 5.0, 10.0, or 15.0 mg/kg), HR rats showed a greater locomotor response than LR rats. Moreover, there was a significant correlation between a subject's locomotor response to the novel environment and the locomotor response to either 10.0 (r = 0.65) or 15.0 (r = 0.92) mg/kg cocaine. In a separate experiment, the extracellular concentration of dopamine in the nucleus accumbens (NACC) was monitored using microdialysis procedures. Following cocaine administration (15.0 mg/kg) HR rats showed a larger NACC dopamine response and greater locomotor activity than LR rats. In addition, there was a threefold greater locomotor activity to dopamine ratio in HR rats than in LR rats. A correlation between a subject's locomotor response to a novel environment and the dopaminergic response to cocaine was also evident. These results suggest that differences in the locomotor response to cocaine can, to some degree, be predicted by a rat's locomotor response to a novel environment, and that variations in dopamine-dependent mechanisms of the NACC may underlie these individual differences.     

A Computer Data Based Management System for a Family Therapy Clinic

This study describes a computer-oriented data based management system designed to be used in a large marriage and family therapy training clinic. The problem was to design a system which would be flexible enough to allow therapists to communicate accurately about their cases as they move between faculty supervisors with diverse theoretical backgrounds. The system was designed to be acceptable to therapists and allows them to enter most of their notes in English prose. Coded entries are kept to a minimum. The system is considered a minimal data system with the gathered material limited to information which is useful in making critical clinical decisions. Information is organized around a Client Data Base, a Treatment Plan which consists of a Problems, Goals and Interventions List, and Progress Notes. The system is also useful for administrative reports and clinical research.     

The influence of depression on the outcome of cardiac phobia (panic disorder)

In a prospectively constructed study 29 patients with cardiac phobia were examined prior to hospitalization and again after a follow-up period of 2.5 years. When first examined a high percentage (82.8%) of these patients showed a depression in addition to suffering from anxiety symptoms. The findings demonstrate that an additional affective disorder constitutes a prognostically unfavorable factor, particularly in the case of a 'secondary' depression. Compared with patients suffering from a 'primary' depression these patients more frequently exhibited a chronic course of the depression (at the 1% level of significance) and had a significantly smaller chance of being free of cardiophobic complaint (p = 0.002) at the last examination. An attempt to categorize cardiac phobia according to DSM-III revealed that the present classification does not provide a satisfactory solution. The frequent presence of a depression in these patients strongly indicates that a clarification of the controversial opinions which continue to exist with regard to a linkage between depressive disorders and anxiety disorders would need further research; in such studies it would seem preferable not to employ a hierarchic classification procedure, in view of the fact that all cross-sectional psychopathological symptoms should be taken into consideration. Our findings also point to the advisability of paying closer attention to course traits in studying this question.     

Auditory P3a deficits in male subjects at high risk for alcoholism.

BACKGROUND: Substantial evidence indicates that alcoholism is biologically mediated by a genetic predisposition. As the decreased P300 (P3b) event-related brain potential component does not recover with prolonged abstinence, it is unlikely to be related to drinking history but is more likely to be genetically influenced. This is supported by findings that P3b amplitudes are reduced in subjects at high-risk compared to low-risk for alcoholism. Although there are few studies of P3a in HR subjects, lower P3a amplitudes have been reported with a novel nontarget stimulus paradigm, as well as with a difficult three-stimulus visual paradigm. Using a similar three-tone auditory paradigm in which the discriminability between the target and standard tone is difficult, the P3a component can also be reliably elicited with a rare nontarget perceptually distinct stimulus. This technique was employed in young adult subjects at low-risk and high-risk for alcoholism. METHODS: A total of 17 low-risk and 24 high-risk male subjects were employed as subjects in an auditory paradigm that yielded a large amplitude P3a with a centro-frontal maximum to the nontarget and a robust low amplitude prolonged P3b with a parietal maximum amplitude to the target stimulus. Current source density maps were derived to assess topographic differences between low-risk and high-risk subjects. RESULTS: The high-risk group manifested significantly lower P3a amplitudes than the low-risk group at the frontal electrodes to rare nontarget stimuli. High-risk subjects also demonstrated a more disorganized current source density map for P3a compared to low-risk subjects. CONCLUSIONS: The reduction of P3a in the high-risk group may be due to cortical dysfunction including the frontal and prefrontal cortex. The lower P3a amplitude coupled with more disorganized current source density maps suggest inefficient brain functioning in high-risk subjects.     

Toward a new approach to mania

After giving a brief summary of the classical psychiatry contribution (taken down a medical pattern of psychiatry diseases) to the knowledge of manic-depressing disorder, the problem of clinical-biological connection to which this classical psychiatry is still confronted is underlined. As a possible answer to this problem, a new approach to mania is possible in a dimensional perspective of the mental disease taking into account the connection model as well as the pathological characteristics within the clinical chart. The notion of integrated behaviour will supply to notion of syndrome (in which all symptoms are equivalents). So, a behaviour dimension, well defined from a clinical analysis connected with a factorial analysis, is proposed as a specific maniac size and as a compartmental aim to the treatments. A dividing of mental pathology in terms of behaviour anomalies should allow a better link between the clinical and the biological.     

A home-based intervention for attentional slips during reading following head injury: A single case study

Abstract

In the absence of evidence of generalisation of computer-based attention training effects to everyday life, a single-case, goal setting methodology employing simple materials was used to train a head-injured subject to reduce the frequency of attention slips during reading. The intervention was carried out at home from 9–13 months post-injury, before the subject attempted to return to work. Training initially led to his being able to read a novel for 5 minutes without a slip when there was no distraction. Further training against background noise led to a statistically significant reduction in frequency of attention slips while reading a technical text, a measure used throughout the study.     

Depression, self-love, time, and the "right" to suicide

Elizabeth Bouvia, whose legal struggle to compel a psychiatric hospital to assist her in committing suicide ended with a decision that she could be force fed by the hospital, presented the psychiatric community with a host of ethical questions concerning the rights of a patient to choose death, and the obligations of the medical profession to promote life. What the courts did not decide is when a patient is incompetent to decide her own fate, and what is the duty of the hospital to intervene with a suicidal patient. The authors suggest that there is an ambiguity present whenever a patient presents herself to a hospital or therapist as suicidal, and that a time limited period, or cooling-off period, should exist that would allow an alliance to form between patient and care-giver, if possible, and then permit them to explore underlying issues of depression. The authors believe that there is a need to acknowledge the patient's ultimate right to choose death, but that autonomy should not be confused with impulsivity when anyone is faced with the irrevocability of the decision to die.     

Mental rotation in a commissurotomized subject

The commissurotomized subject L.B. showed a strong right-hemispheric advantage on a task requiring him to judge rotated letters normal or backward, but a left-hemispheric advantage in a task requiring discrimination of the same letters, implying that the right-hemispheric advantage has to do with mental rotation. However, his right hemisphere proved unable to perform a task requiring mental rotation of a simple unfamiliar pattern to a designated "upright", and was inferior to the left on a task requiring two such patterns, at varying orientations relative to one another, to be judged same or different. We suggest that the deficiency of the right hemisphere on these tasks was unrelated to mental rotation per se, but reflected a failure to comprehend the tasks properly.     

The attractive but illusory autonomy of a one-sided explanatory model for the psychopathology

Nowadays psychiatry is dominated by the scientific perspective of biological psychiatry according to which a psychiatrist should be first and foremost a brain specialist with a biomedical approach to patients and their problems. This constitutes a threat to the fundamental notion that a psychiatrist is concerned primarily with the workings of the mind and it reduces the discipline to a form of behavioural neurology. This restrictive interpretation fails to do justice to the theory that psychopathology has a multitude of causes. This article provides an overview of the methodological, socio-cultural and metaphysical causes and effects of this one-sided development. The overview is followed by a plea for a pluralistic rather than a deterministic view of psychiatry, which is an extraordinary type of medical discipline.     

"Say Cheese": teaching photography skills to adults with developmental disabilities

We evaluated a video prompting procedure to teach adults with developmental disabilities to take a digital photograph and print it using a laptop computer and a printer. Participants were four men with developmental disabilities. Training was conducted at the participants’ residential facility. During baseline, participants were told to take a photograph, but were given no other instruction. During intervention, participants received instruction using a video prompting procedure. Video prompting consisted of watching a clip of each step of the task analysis and then having the opportunity to imitate that step. Video prompting was evaluated using a multiple-probe across participants design. Following acquisition, video prompting was removed to assess maintenance at 2, 4 and 8 weeks and at 6 months. During naturalistic probes, participants had the opportunity to take a picture of their choice of flora, surroundings or persons. All four participants learned to take and print a digital photograph with the video prompting procedures. The skills generalized to novel situations and were maintained at each follow-up probe. These data suggest that video prompting may be an effective instructional strategy for teaching digital photography skills to adults with developmental disabilities.     

A recurrent neural network: Limitations and training

A recurrent, synchronous neural network is treated as a collection of independent perceptrons. The dynamics of the network can be described by a mapping: a finite set of transitions in the state space of the network. We define legal mapping as a mapping that a synchronous neural network is able to perform, and state the necessary and sufficient conditions for a mapping to be legal. A learning algorithm for the network, based on the perceptron's learning algorithm, is guaranteed to converge to a solution when the network is trained to realize a legal mapping. It is shown that the algorithm performs a gradient descent search for a minimum of a cost function that is a certain error measure in the weight space. Performance of the algorithm for the associative memory application and for temporal sequences production is illustrated by numerical simulations. A method is proposed for legalizing any given mapping at the expense of adding a finite number of neurons to the network. It is also shown that when the number of transitions in a random mapping is less than the number of neurons in the network, the probability that such a mapping is legal approaches unity.     

Orientation detectors in the primary somatosensory neocortex of the raccoon.

An analysis of response properties of single neurons in the forepaw region of the primary somatosensory neocortex (SI) of the raccoon was undertaken to gain a better understanding of the neural bases of tactile form discrimination. In the course of this investigation a new type of feature detector neuron which responded preferentially to tactile stimulus orientation was discovered. Within a sample of 110 neurons responding to light touch, two categories of cells were noted in terms of the type of stimulation best able to excite them. One category (linear units) was preferentially responsive to indentations of the skin using a narrow elongated stimulus probe applied in a particular orientation. The other category (round field units) gave a maximum response to stimulation with a round stimulus probe applied anywhere within a roughly circular receptive field. The response pattern of some SI neurons to a maintained indentation of the skin consisted of early and late excitatory responses, separated by a depression in responding. The second excitatory response appeared to be more influenced by variations in stimulus parameters than was the first.     

Truly a team effort

Jane was a healthy 16 year old girl who attended a high school dance and subsequently had a grand mal seizure--her first! She was taken home, developed a decreasing level of consciousness and was admitted to the local hospital, where it progressed to status epilepticus. We will describe the classifications of seizures including status epilepticus, which demands the highest level of clinical expertise and attention to preventative medicine, for a desirable outcome. During the eleven months of care a massive multi disciplinary team approach was instituted which extended across borders. Jane's story demonstrates a truly Neuroscience team effort from acute care to a rehabilitation center to home.     

Visually guided behavior of monkeys after early binocular visual deprivation

Four infant monkeys were binocularly deprived of vision through their first year of life. After the end of the deprivation their visually guided behavior was followed for one year. Behavioral tests were performed to assess their visual functions. The performance of the deprived monkeys was compared with the performance of three normally sighted monkeys. The following functions were tested: the monkey's ability to detect a moving light spot, to track a moving object, to grasp an object, to chatter the teeth in response to a threatening face, to pick pellets from a board, to respond to a sudden visual threat and to move about in a wide space. The visually deprived monkeys remained severely visually handicapped. They were able to detect a moving light spot in a darkened room and to recognize the movement of large objects. However, they continued bumping into objects and used tactile exploration when moving about in a wide space. They never learned to respond to a threatening face, which for a normal monkey is part of the normal behavioral repertoires. The persistently poor visually guided behavior of these monkeys is in agreement with the electrophysiological findings in the posterior parietal association cortex of these monkeys; early visual deprivation permanently reduces the number of visually responsive cell groups in this association area.     

Does placebo help establish equivalence in trials of new antidepressants?

Clinical trials of new antidepressants usually compare a new drug to a reference antidepressant and to a placebo. The placebo is intended to validate the trial in the case of a no-difference outcome, i.e., it helps in assessing equivalence. The aim of the present paper is to test whether placebo has indeed helped establish equivalence of effect in comparative trials of new antidepressants. We carried out an example of sample size determination first in a trial to show a difference between the new and control drug, and second in a trial to assess equivalence between two competing drugs. Finally, we retrospectively calculated the maximum difference accepted as equivalence of effect in published trials of new antidepressants. Assuming a response rate to antidepressants of 70%, 294 subjects for each treatment group are needed to show a 10% difference between two antidepressant drugs and more than 1,300 to assess equivalence at a 5% level of delta, the maximum difference acceptable as equivalence of effect. The level of delta in published trials of new antidepressants ranges between 12 and 43%, suggesting they cannot claim to demonstrate equivalence of effect. Therefore, the presence of a placebo arm for comparison didn't help establish whether both drugs really worked the same way. Comparative trials of new antidepressants should adopt a two-arm design, a suitable number of patients and a high standard in the experimental design in order to minimise possible control-event rate variation.     

Visually based path-planning by Japanese monkeys

To construct an animal model of strategy formation, we designed a maze path-finding task. First, we asked monkeys to capture a goal in the maze by moving a cursor on the screen. Cursor movement was linked to movements of each wrist. When the animals learned the association between cursor movement and wrist movement, we established a start and a goal in the maze, and asked them to find a path between them. We found that the animals took the shortest pathway, rather than approaching the goal randomly. We further found that the animals adopted a strategy of selecting a fixed intermediate point in the visually presented maze to select one of the shortest pathways, suggesting a visually based path planning. To examine their capacity to use that strategy flexibly, we transformed the task by blocking pathways in the maze, providing a problem to solve. The animals then developed a strategy of solving the problem by planning a novel shortest path from the start to the goal and rerouting the path to bypass the obstacle.     

Neuroapoptosis in the infant mouse brain triggered by a transient small increase in blood alcohol concentration

Exposure of infant rats or mice to ethanol on a single occasion during the period of rapid synaptogenesis can cause extensive apoptotic neurodegeneration throughout the developing CNS. Prior studies were designed to assess the effects of large doses of ethanol (comparable to heavy binge drinking), whereas in the present study, we sought to determine what magnitude and duration of blood ethanol elevation are required to trigger a minimal neuroapoptotic response. We found that a rise in blood ethanol to a level in the range of 50 mg/dl for a duration of 30 to 45 min was sufficient to trigger a significant neuroapoptosis response deleting approximately 20,000 neurons per infant mouse brain. Since blood ethanol elevations in this range are commonly achieved by humans in a social drinking context, a mother with only a moderate drinking habit might expose her fetus to such elevations on multiple occasions during pregnancy.     

Communication and knowledge sharing in human–robot interaction and learning from demonstration

Inexpensive personal robots will soon become available to a large portion of the population. Currently, most consumer robots are relatively simple single-purpose machines or toys. In order to be cost effective and thus widely accepted, robots will need to be able to accomplish a wide range of tasks in diverse conditions. Learning these tasks from demonstrations offers a convenient mechanism to customize and train a robot by transferring task related knowledge from a user to a robot. This avoids the time-consuming and complex process of manual programming. The way in which the user interacts with a robot during a demonstration plays a vital role in terms of how effectively and accurately the user is able to provide a demonstration. Teaching through demonstrations is a social activity, one that requires bidirectional communication between a teacher and a student. The work described in this paper studies how the user’s visual observation of the robot and the robot’s auditory cues affect the user’s ability to teach the robot in a social setting. Results show that auditory cues provide important knowledge about the robot’s internal state, while visual observation of a robot can hinder an instructor due to incorrect mental models of the robot and distractions from the robot’s movements.