Search PubMed⌕ Search

Biomedical subjects

D Bullock

Publications and source records attributed to D Bullock.

At least 19 recordsLinked to original sources

A model of movement coordinates in the motor cortex: posture-dependent changes in the gain and direction of single cell tuning curves.

This article outlines a methodology for investigating the coordinate systems by which movement variables are encoded in the firing rates of individual motor cortical neurons. Recent neurophysiological experiments have probed the issue of underlying coordinates by examining how cellular preferred directions (as determined by the center-out task) change with posture. Several key experimental findings have resulted that constrain hypotheses about how motor cortical cells encode movement information. But while the significance of shifts in preferred direction is well known and widely accepted, posture-dependent changes in the depth of modulation of a cell's tuning curve--that is, gain changes--have not been similarly identified as a means of coordinate inference. This article develops a vector field framework in which the preferred direction and the gain of a cell's tuning curve are viewed as dual components of a unitary response vector. The formalism can be used to compute how each aspect of cell response covaries with posture as a function of the coordinate system in which a given cell is hypothesized to encode its movement information. Such an integrated approach leads to a model of motor cortical cell activity that codifies the following four observations: (i) cell activity correlates with hand movement direction; (ii) cell activity correlates with hand movement speed; (iii) preferred directions vary with posture; and (iv) the modulation depth of tuning curves varies with posture. Finally, the model suggests general methods for testing coordinate hypotheses at the single-cell level and simulates an example protocol for three possible coordinate systems: Cartesian spatial, shoulder-centered, and joint angle.

Animals↗

Health-related quality-of-life measure enhances acute treatment response prediction in depressed inpatients.

BACKGROUND: Many nonbiological variables are reported to predict treatment response for major depression; however, there is little agreement about which variables are most predictive. METHOD: Inpatient subjects (N = 59) diagnosed with current DSM-IV major depressive disorder completed weekly depressive symptom ratings with the Hamilton Rating Scale for Depression (HAM-D-17) and Beck Depression Inventory (BDI), and weekly health-related quality-of-life (HRQL) ratings with the Quality of Well-Being Scale (QWB). Acute responders were identified by a 50% decrease in HAM-D-17 score from baseline within 4 weeks of medication treatment. Predictor variables were initially chosen from a literature review and then tested for their association with acute treatment response. RESULTS: An initial predictive model including age at first depression, admission BDI score, and melancholia predicted acute treatment response with 69% accuracy and was designated as the benchmark model. Adding the admission QWB index score to the benchmark model did not improve the prediction rate; however, adding the admission QWB subscales for physical and social activity to the benchmark model significantly improved acute treatment response prediction to 86% accuracy (p = .001). CONCLUSION: In addition to being designed for use in cost-effectiveness analyses, the QWB subscales appear to be useful HRQL variables for predicting acute inpatient depression treatment response.

Adult↗

Kinematic coordinates in which motor cortical cells encode movement direction.

During goal-directed reaching in primates, a sensorimotor transformation generates a dynamical pattern of muscle activation. Within the context of this sensorimotor transformation, a fundamental question concerns the coordinate systems in which individual cells in the primary motor cortex (MI) encode movement direction. This article develops a mathematical framework that computes, as a function of the coordinate system in which an individual cell is hypothesized to operate, the spatial preferred direction (pd) of that cell as the arm configuration and hand location vary. Three coordinate systems are explicitly modeled: Cartesian spatial, shoulder-centered, and joint angle. The computed patterns of spatial pds are distinct for each of these three coordinate systems, and experimental approaches are described that can capitalize on these differences to compare the empirical adequacy of each coordinate hypothesis. One particular experiment involving curved motion was analyzed from this perspective. Out of the three coordinate systems tested, the assumption of joint angle coordinates best explained the observed cellular response properties. The mathematical framework developed in this paper can also be used to design new experiments that are capable of disambiguating between a given set of specified coordinate hypotheses.

Animals↗

How the basal ganglia use parallel excitatory and inhibitory learning pathways to selectively respond to unexpected rewarding cues.

After classically conditioned learning, dopaminergic cells in the substantia nigra pars compacta (SNc) respond immediately to unexpected conditioned stimuli (CS) but omit formerly seen responses to expected unconditioned stimuli, notably rewards. These cells play an important role in reinforcement learning. A neural model explains the key neurophysiological properties of these cells before, during, and after conditioning, as well as related anatomical and neurophysiological data about the pedunculopontine tegmental nucleus (PPTN), lateral hypothalamus, ventral striatum, and striosomes. The model proposes how two parallel learning pathways from limbic cortex to the SNc, one devoted to excitatory conditioning (through the ventral striatum, ventral pallidum, and PPTN) and the other to adaptively timed inhibitory conditioning (through the striosomes), control SNc responses. The excitatory pathway generates CS-induced excitatory SNc dopamine bursts. The inhibitory pathway prevents dopamine bursts in response to predictable reward-related signals. When expected rewards are not received, striosomal inhibition of SNc that is unopposed by excitation results in a phasic drop in dopamine cell activity. The adaptively timed inhibitory learning uses an intracellular spectrum of timed responses that is proposed to be similar to adaptively timed cellular mechanisms in the hippocampus and cerebellum. These mechanisms are proposed to include metabotropic glutamate receptor-mediated Ca(2+) spikes that occur with different delays in striosomal cells. A dopaminergic burst in concert with a Ca(2+) spike is proposed to potentiate inhibitory learning. The model provides a biologically predictive alternative to temporal difference conditioning models and explains substantially more data than alternative models.

Animals↗

Development in a biologically inspired spinal neural network for movement control.

In two phases, we develop increasingly complex neural network models of spinal circuitry that self-organizes into networks with opponent channels for the control of an antagonistic muscle pair. The self-organization is enabled by a Hebbian learning rule operating during spontaneous activity present in the spinal cord. After the self-organized development, the networks enable independent control of the length and tension of the innervated muscles. This allows higher centers to hold joint angle invariant while varying joint stiffness and vice versa. The first network comprises only spontaneous activity generators, motorneurons, and inhibitory interneurons through which the two channels interact. The inhibitory interneurons enhance reciprocal action, and prevent saturation of the motorneuron pools, which is a necessary condition for independent control. In the second network, the neurons in the motorneuron pools obey the size-principle, which, when added by itself, leads to a loss of the desired invariance property. To restore the desired invariance, the second network further incorporated inhibitory interneurons analogous to Renshaw cells. The results obtained from the two models compare favourably with the FLETE-model for spinal circuitry ([Bullock and Contreras-Vidal, 1993]; [Bullock et al., 1992]; [Bullock and Grossberg, 1991]) which, although successful in explaining several phenomena related to motor control, did not self-organize its connection weights. Finally, we suggest ways in which this research could be applied in technology.

Journal Article↗

A cortico-spinal model of reaching and proprioception under multiple task constraints.

A model of cortico-spinal trajectory generation for voluntary reaching movements is developed to functionally interpret a broad range of behavioral, physiological, and anatomical data. The model simulates how arm movements achieve their remarkable efficiency and accuracy in response to widely varying positional, speed, and force constraints. A key issue in arm movement control is how the brain copes with such a wide range of movement contexts. The model suggests how the brain may set automatic and volitional gating mechanisms to vary the balance of static and dynamic feedback information to guide the movement command and to compensate for external forces. For example, with increasing movement speed, the system shifts from a feedback position controller to a feedforward trajectory generator with superimposed dynamics compensation. Simulations of the model illustrate how it reproduces the effects of elastic loads on fast movements, endpoint errors in Coriolis fields, and several effects of muscle tendon vibration, including tonic and antagonist vibration reflexes, position and movement illusions, effects of obstructing the tonic vibration reflex, and reaching undershoots caused by antagonist vibration.

Computer Simulation↗

A neural model of multimodal adaptive saccadic eye movement control by superior colliculus.

How does the saccadic movement system select a target when visual, auditory, and planned movement commands differ? How do retinal, head-centered, and motor error coordinates interact during the selection process? Recent data on superior colliculus (SC) reveal a spreading wave of activation across buildup cells the peak activity of which covaries with the current gaze error. In contrast, the locus of peak activity remains constant at burst cells, whereas their activity level decays with residual gaze error. A neural model answers these questions and simulates burst and buildup responses in visual, overlap, memory, and gap tasks. The model also simulates data on multimodal enhancement and suppression of activity in the deeper SC layers and suggests a functional role for NMDA receptors in this region. In particular, the model suggests how auditory and planned saccadic target positions become aligned and compete with visually reactive target positions to select a movement command. For this to occur, a transformation between auditory and planned head-centered representations and a retinotopic target representation is learned. Burst cells in the model generate teaching signals to the spreading wave layer. Spreading waves are produced by corollary discharges that render planned and visually reactive targets dimensionally consistent and enable them to compete for attention to generate a movement command in motor error coordinates. The attentional selection process also helps to stabilize the map-learning process. The model functionally interprets cells in the superior colliculus, frontal eye field, parietal cortex, mesencephalic reticular formation, paramedian pontine reticular formation, and substantia nigra pars reticulata.

Animals↗

Metabotropic glutamate receptor activation in cerebellar Purkinje cells as substrate for adaptive timing of the classically conditioned eye-blink response.

To understand how the cerebellum adaptively times the classically conditioned nictitating membrane response (NMR), a model of the metabotropic glutamate receptor (mGluR) second messenger system in cerebellar Purkinje cells is constructed. In the model, slow responses, generated postsynaptically by mGluR-mediated phosphoinositide hydrolysis and calcium release from intracellular stores, bridge the interstimulus interval (ISI) between the onset of parallel fiber activity associated with the conditioned stimulus (CS) and climbing fiber activity associated with unconditioned stimulus (US) onset. Temporal correlation of metabotropic responses and climbing fiber signals produces persistent phosphorylation of both AMPA receptors and Ca(2+)-dependent K+ channels. This is responsible for long-term depression (LTD) of AMPA receptors. The phosphorylation of Ca(2+)-dependent K+ channels leads to a reduction in baseline membrane potential and a reduction of Purkinje cell population firing during the CS-US interval. The Purkinje cell firing decrease disinhibits cerebellar nuclear cells, which then produce an excitatory response corresponding to the learned movement. Purkinje cell learning times the response, whereas nuclear cell learning can calibrate it. The model reproduces key features of the conditioned rabbit NMR: Purkinje cell population response is timed properly; delay conditioning occurs for ISIs of up to 4 sec, whereas trace conditioning occurs only at shorter ISIs; mixed training at two different ISIs produces a double-peaked response; and ISIs of 200-400 msec produce maximal responding. Biochemical similarities between timed cerebellar learning and photoreceptor transduction, and circuit similarities between the timed cerebellar circuit and a timed dentate-CA3 hippocampal circuit, are noted.

Animals↗

Resource utilization and pathways: meeting the challenge of cost containment.

The 1990s will bring sweeping changes with managed care and capitation. To address this cost/quality paradox, selective intensive care utilization is coupled with clinical pathways as an innovative change for all patients having cerebral revascularization (CVR) or femoral revascularization (FR). From January 1, 1991 through June 30, 1995, data were accumulated on 2023 procedures in 1524 patients. The study was based on 848 CVRs and 1175 FRs. Intensive care unit (ICU) observation was necessary in 73 patients (3.6%) for cardiac or hypertensive management. Twenty-six patients (1.2%) transported to a vascular surgical floor from the postanesthesia recovery room required return to an ICU for complications during hospitalization. There were nine strokes or transient ischemic attacks (0.4%) in the CVR group, four myocardial infarctions (0.2%), and five perioperative deaths (0.3%). In the FR group, there were 14 deaths (0.9%). Readmission during the perioperative period, 30 days, was necessary in 46 patients (3.1%). Financial cost analysis revealed the mean adjusted cost for CVR in 1990 adjusted to 1995 dollars was $7223. The institution of case management reduced this to $4490 (37.8 per cent reduction in total hospital costs). The cost for FR in 1990 dollars adjusted to 1995 was $14,332 reduced to $5541 (a 59 per cent reduction in total hospital costs). This study suggests the use of clinical pathways does not impair quality of care, leads to no higher morbidity or mortality, and can produce significant cost savings to a hospital.

Aged↗

Neural representations for sensory-motor control, I: Head-centered 3-D target positions from opponent eye commands.

This article describes how corollary discharges from outflow eye movement commands can be transformed by two stages of opponent neural processing into a head-centered representation of 3-D target position. This representation implicitly defines a cyclopean coordinate system whose variables approximate the binocular vergence and spherical horizontal and vertical angles with respect to the observer's head. Various psychophysical data concerning binocular distance perception and reaching behavior are clarified by this representation. The representation provides a foundation for learning head-centered and body-centered invariant representations of both foveated and non-foveated 3-D target positions. It also enables a solution to be developed of the classical motor equivalence problem, whereby many different joint configurations of a redundant manipulator can all be used to realize a desired trajectory in 3-D space.

Brain↗

Reconciling stable asymmetry with recovery of function: an adaptive systems perspective on functional plasticity.

This article examines alternative ways of resolving an apparent paradox that has emerged from neuropsychological studies of language development: How can the developmentally stable functional asymmetry ("hemispheric specialization") observed in neurologically intact children be reconciled with the dramatic recovery of function often displayed following unilateral brain damage? The alternative resolutions we consider differ most critically in the roles they assign to lesion-induced neural reorganizations versus lesion-related release of preexisting functional potentials. Though arguments are given in favor of the latter as the primary factor in functional recovery, the primary goal of the article is to clarify the conceptual issues raised by recent empirical research.

Brain↗

Adduction contracture of the thumb in cerebral palsy. A preoperative electromyographic study.

In twenty-three patients with cerebral palsy and functional spastic hemiplegia, the contracted thenar-adductor space of the involved hand was evaluated by electromyography. The needle electromyogram was used to determine if the patient had selective control of the adductor muscle. In eight patients only partial myotomy of the adductor muscle during z-plasty of the web was performed because selective control of that muscle was present during either grasp or release. In four patients a complete release was done, and in two of them the ability to pinch was impaired.

Adolescent↗

The impact of personal preference on consistency through time: the case of childhood aggression.

The present experiment was designed to test the hypothesis that a child's activity preferences may predict subsequent changes in that child's aggression, since such preferences partly determine how children allocate their time to situations capable of making them more or less aggressive. Data from a 1-year longitudinal study reveal that (1) boys vary widely in the extent of their preference for aggression-conducive situations. (2) girls have low preference for such situations, and (3) preference has a strong impact on the development of aggression in boys who have not already become either very high or very low in aggression. This phenomenon provides an example of an interestng developmental pattern: Temporal stability in 1 personal characteristic (e.g., preference structure) can lead to directed transformation of another personal characteristic (e.g., typical interpersonal behavior).

Aggression↗

A comparative trial of pivmecillinam and ampicillin in bacteriuria of pregnancy.

A comparative trial of pivmecillinam and ampicillin was performed on 100 women with bacteriuria of pregnancy. They received either 400 mg pivmecillinam four times daily or 500 mg ampicillin four times daily for seven days. Cure rates at two weeks were 88% in the pivmecillinam group and 85% in the ampicillin group. At six weeks the respective rates were 76% and 64%. Failure of therapy was not associated with the appearance of bacterial resistance in either treatment group. Side-effects, particularly vomiting and premature cessation of therapy, were significantly more frequent in the pivmecillinam group. No significant effects on liver function were found. In subsequent patients treated in a non-comparative manner with 200 mg pivmecillinam three times daily, the incidence of side effects was markedly reduced with no loss of efficacy.

Amdinocillin Pivoxil↗

Guidelines for family interviewing and brief therapy by the family physician.

Psychosomatic and behavioral problems are commonly seen in the practice of family medicine. If these problems are viewed as difficulties with family interaction, rather than as difficulties of an individual family member, intervention may be more successful. Treatment of families with problems involves interviewing the family unit, identifying and altering dysfunctional behavioral patterns within the family which serve to maintain the problem, and making selected referrals to experienced family therapists.

Behavior↗

School phobia.

Pediatricians and other primary care providers are in an ideal position to prevent, to diagnose and to treat children with school refusal. Detection requires recognition of high risk situations, and delineation of possible reality factors or environmental hazards. The physician will find school refusal associated with perceived or actual physical illness, debility, or vulnerability, family stresses including illnesses and marital problems, over-protective mother-child interaction patterns, and previous difficulties in achieving mother-child independence and separation. Confirming the diagnosis depends on interview with family members. Positive indicators are dysfunctional patterns of family communication, parental emphasis on illness, and manipulative behavior on the part of the child. Data from the school on absenteeism need to be supplemented by the school's observations of individual achievement and ability measures, grades, and teacher observations of peer and adult interaction. Treatment techniques center around returning the child to school by involving the child, the family, and the school in this process. Specific counseling techniques and principles aim to recognize each individual's feelings and to stress the active role of the parents in solving problems together. Follow-up is based upon assessment of clearly understood short-term and long-term goals. Referral should be rare, and should not be undertaken before proper evaluation has been completed. Making a referral "stick" depends greatly upon the degree of rapport and trust which has been established with the family. In most school refusal cases, management by the pediatrician or primary physician can be a rewarding, stimulating experience which provides a high degree of parent and physician satisfaction.

Adolescent↗