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Biomedical subjects

P W Glimcher

Publications and source records attributed to P W Glimcher.

17 recordsLinked to original sources
PubMed2001

Application of neurosonography to experimental physiology.

When Horsley and Clark invented the stereotaxic technique they revolutionized experimental neurobiology. For the first time it became possible to repeatably place experimental or surgical probes at precise locations within the skull. Unfortunately, variations in the position and size of neuroanatomical structures within the cranium have always limited the efficiency of this technology. Recent advances in diagnostic medical ultrasonography, however, allow for the real-time visualization of anatomical structures, in some cases with resolutions of up to 150 microm. We report here that commercially available ultrasonographs can be used in the laboratory to generate real-time in vivo images of brain structures in both anesthetized and awake-behaving animals. We found that ultrasonic imaging is compatible with many types of experimental probes including single neuron recording electrodes, microinjection pipettes, and electrodes for producing electrolytic lesions. Ultrasonic imaging can be used to place, monitor and visualize these probes in vivo. In our hands, commercially available ultrasonic probes designed for pediatric use allowed us to visualize anatomical structures with sub-millimeter resolution in primate brains. Finally, ultrasonic imaging allowed us to reduce the risk of accidentally damaging major blood vessels, greatly reducing the incidence of stroke as an unintended complication of an experimental neurosurgical procedure. Diagnostic ultrasound holds the promise of reducing the uncertainty associated with stereotaxic surgery, an improvement which would significantly improve the efficiency of many neurobiological investigations, reducing the number of animal subjects employed in this research. While this demonstration focuses on sonographic imaging in non-human primates, similar advances should also be possible for studies in other species, including rodents.

Animals↗
PubMed2001

Stimulus probability directs spatial attention: an enhancement of sensitivity in humans and monkeys.

We examined whether improvements in sensory processing, defined as changes in sensitivity, could be elicited in a simple luminance discrimination task without eliciting concomitant changes in decision processing. To this end we developed a task, for use in both humans and monkeys, in which prior knowledge about where a discriminative stimulus was likely to appear (1) offered no decisional advantage in solving our task and (2) could be parametrically varied to yield a psychometric function. We found that if we parametrically varied the quality of prior knowledge, by increasing the probability, and thus the certainty, that a discriminative stimulus would appear at a particular location under these conditions, luminance discrimination improved for both human and monkey subjects. This improvement was correlated with an enhancement in sensory processing, but not with any systematic changes in decisional processing, as assessed by signal detection theory. These results suggest that (1) sensory processing and decision processing can be separated by task design and (2) systematic changes in prior knowledge about where a stimulus may appear can lead to systematic changes in sensitivity; providing a psychometric function for the influence of prior knowledge on perceptual sensitivity. Importantly, these results were obtained from both human and monkey subjects. Similar task designs could be used in physiological studies attempting to generate linking hypotheses between psychometric and neurometric functions, ultimately allowing changes in perceptual sensitivity to be linked to changes in an underlying neural substrate.

Adult↗
PubMed2001

Making choices: the neurophysiology of visual-saccadic decision making.

Imagine the decisions you might make while playing a simple game like 'matching pennies'. At each play, you and your opponent, say the mathematician John vonNeumann, each lay down a penny heads or tails up. If both pennies show the same side, vonNeumann wins, if not, you win. Before each play, you have the subjective experience of deciding what to do: of choosing whether to play heads or tails. Although decisions like these are not yet understood at a physiological level, progress has been made towards understanding simple decision making in at least one model system: the primate neural architecture that uses visual data and prior knowledge about patterns in the environment to select and execute saccades. Both the visual system and the brainstem circuits that control saccadic eye movements are particularly well understood, making it possible for physiologists to begin to study the connections between these sensory and motor processes at a level of complexity that would be impossible in other less well understood systems.

Choice Behavior↗
PubMed2000

Short-term changes in movement frequency do not alter the spatial tuning of saccade-related neurons in intraparietal cortex.

Modulations of the firing rates of neurons in the lateral intraparietal area (LIP) have been observed during experiments designed to examine decision-processing, movement planning, and visual attention. These modulations have been assumed to reflect a uniform scaling of spatially stationary response fields, which describe firing rate as a function of either visual target location or movement metrics. However, because complete response fields are rarely collected, the possibility exists that these modulations may reflect shifts in response field location or changes in response field size. Moreover, many of these observed changes in LIP neuronal activity are also correlated with experimental practices that alter the frequency with which particular visual stimuli are viewed and particular movements are produced. The effects of repeatedly presenting a particular target and eliciting a particular movement on the response fields of LIP neurons warrant closer inspection because manipulations of this type are known to alter both the location and size of the receptive fields of many cortical sensory neurons. To address this issue, we measured the response fields of neurons in intraparietal cortex under two conditions over a period of up to 2 h: one in which each of nearly 200 stimulus locations was equally likely to serve as the saccade target on a trial, and a second in which one stimulus location was up to 750 times likelier to serve as the saccade target on a trial than were any of the other stimulus locations. We found no shifts in response field location or changes in response field size when we altered the frequency with which particular movements were produced or particular visual stimuli were presented. These data suggest that the response fields of intraparietal neurons are stationary over short periods of time and under conditions similar to those typically used to study LIP neuronal activity.

Animals↗
PubMed2000

Contextual modulation of substantia nigra pars reticulata neurons.

Neurons in the substantia nigra pars reticulata (SNr) are known to encode saccadic eye movements within some, but not all, behavioral contexts. However, the precise contextual factors that effect the modulations of nigral activity are still uncertain. To further examine the effect of behavioral context on the SNr, we recorded the activity of 72 neurons while monkeys made saccades during a delayed saccade task and during periods of free viewing. We quantified and compared the movement fields of each neuron for saccades made under three different conditions: 1) spontaneous saccades, which shifted gaze during periods of free viewing when no stimuli were presented and no reinforcements were delivered; 2) fixational saccades, which brought gaze into alignment with a fixation target at the start of a delayed saccade trial, were necessary for trial completion, but were not directly followed by reinforcement; and 3) terminal saccades, which brought gaze into alignment with a visual target at the end of a delayed saccade trial and were directly followed by reinforcement. For three of the four SNr neuron classes, saccade-related modulations were only present before terminal saccades. For the fourth class, discrete pausers, saccade-related modulations were substantially larger for terminal saccades than for fixational saccades, and modulations were absent for spontaneous saccades. These results and other recent work on the basal ganglia suggest that some saccade-related signals in the SNr may be influenced by the reinforcement associated with a particular saccadic eye movement.

Action Potentials↗
PubMed1999

Neural correlates of decision variables in parietal cortex.

Decision theory proposes that humans and animals decide what to do in a given situation by assessing the relative value of each possible response. This assessment can be computed, in part, from the probability that each action will result in a gain and the magnitude of the gain expected. Here we show that the gain (or reward) a monkey can expect to realize from an eye-movement response modulates the activity of neurons in the lateral intraparietal area, an area of primate cortex that is thought to transform visual signals into eye-movement commands. We also show that the activity of these neurons is sensitive to the probability that a particular response will result in a gain. When animals can choose freely between two alternative responses, the choices subjects make and neuronal activation in this area are both correlated with the relative amount of gain that the animal can expect from each response. Our data indicate that a decision-theoretic model may provide a powerful new framework for studying the neural processes that intervene between sensation and action.

Animals↗
PubMed1999

Quantitative analysis of substantia nigra pars reticulata activity during a visually guided saccade task.

Several lines of evidence suggest that the pars reticulata subdivision of the substantia nigra (SNr) plays a role in the generation of saccadic eye movements. However, the responses of SNr neurons during saccades have not been examined with the same level of quantitative detail as the responses of neurons in other key saccadic areas. For this report, we examined the firing rates of 72 SNr neurons while awake-behaving primates correctly performed an average of 136 trials of a visually guided delayed saccade task. On each trial, the location of the visual target was chosen randomly from a grid spanning 40 degrees of horizontal and vertical visual angle. We measured the firing rates of each neuron during five intervals on every trial: a baseline interval, a fixation interval, a visual interval, a movement interval, and a reward interval. We found four distinct classes of SNr neurons. Two classes of neurons had firing rates that decreased during delayed saccade trials. The firing rates of discrete pausers decreased after the onset of a contralateral target and/or before the onset of a saccade that would align gaze with that target. The firing rates of universal pausers decreased after fixation on all trials and remained below baseline until the delivery of reinforcement. We also found two classes of SNr neurons with firing rates that increased during delayed saccade trials. The firing rates of bursters increased after the onset of a contralateral target and/or before the onset of a saccade aligning gaze with that target. The firing rates of pause-bursters increased after the onset of a contralateral target but decreased after the illumination of an ipsilateral target. Our quantification of the response profiles of SNr neurons yielded three novel findings. First, we found that some SNr neurons generate saccade-related increases in activity. Second, we found that, for nearly all SNr neurons, the relationship between firing rate and horizontal and vertical saccade amplitude could be well described by a planar surface within the range of movements we sampled. Finally we found that for most SNr neurons, saccade-related modulations in activity were highly variable on a trial-by-trial basis.

Acoustic Stimulation↗
PubMed1998

Response fields of intraparietal neurons quantified with multiple saccadic targets.

The activity of each of 99 intraparietal neurons was studied in three awake-behaving rhesus monkeys (Macaca mulatta) while subjects performed 100-900 delayed saccade trials. On each trial, a saccadic target was presented at one location selected randomly from a grid of 441 locations spanning 40 degrees of horizontal and vertical visual space. Individual neurons in our population were sensitive to both the direction and amplitude of saccades. Response fields, which plotted firing rate as a function of the horizontal and vertical amplitude of movements for each neuron, were characterized by a Cartesian two-dimensional gaussian model. The goodness-of-fit of these gaussian models was tested by: (1) comparing observed responses with predicted responses for each movement; and (2) by computing the percentage of variance explained by each model. Cartesian Gaussian models provided a good fit to the response fields of most neurons. Across our population, the Gaussian fit to the response field of each neuron accounted for more of the variance in neuronal activity when the data were plotted with regard to the horizontal and vertical amplitude of the saccade than when the same data were plotted with regard to the position of the saccadic target. The Gaussian functions were used to estimate the eccentricity and spatial tuning breadth of each neuronal response field. Modal response field radius was less than 5 degrees, whereas mean response field radius was about 10 degrees. Linear regression analysis demonstrated that response field eccentricity accounted for less than 30% of the variance in response field radius. Analysis of the horizontal distribution of response field centers showed an approximately normal distribution around central fixation. Most histologically recovered neurons were located on the lateral bank of the intraparietal sulcus, although a small number of saccade-related neurons were recorded from Brodmann's area 5 on the medial bank of the intraparietal sulcus.

Animals↗
PubMed1997

Responses of intraparietal neurons to saccadic targets and visual distractors.

Current evidence suggests that neuronal activity in the lateral intraparietal area (LIP) reflects sensory-motor processes, but it remains unclear whether LIP activation participates directly in the planning of future eye movements or encodes data about both sensory events and the behavioral significance of those sensory events. To examine this issue, 31 intraparietal neurons were studied in awake, behaving monkeys trained to perform two tasks that independently controlled the location of a saccadic target and the location and behavioral relevance of a visual distractor. In both of these tasks, two eccentric light-emitting diodes (LEDs) were illuminated yellow, one above and one below a fixation stimulus. Shortly after the eccentric LEDs were illuminated, a change in the color of the fixation stimulus indicated which of these LEDs served as the saccadic goal and which served as a visual distractor. In the first or distractor-irrelevant task, fixation offset indicated that the subject must initiate a saccade shifting gaze to the saccadic goal. In the second or distractor-relevant task, distractor offset served as the saccade initiation cue. Intraparietal neurons responded more strongly in association with an LED that served as a saccadic target than in association with the same LED when it served as a visual distractor. Neuronal responses in association with either target or distractor stimuli on distractor-relevant and distractor-irrelevant blocks of trials were statistically indistinguishable. When the location of either the target or the distractor was varied across trials, the response of each neuron in association with a particular stimulus location was always greater for targets than for distractors and the magnitude of this response difference was independent of distractor relevance; however, distractors were nearly always associated with some intraparietal neuronal activity. A target/distractor selectivity index was computed for each neuron as the difference between responses associated with targets minus responses associated with distractors divided by the sum of these values. When the selectivity of each neuron on the distractor-relevant task was plotted against the selectivity of the same neuron on the distractor-irrelevant task, activity in the population of intraparietal neurons was found to be independent of distractor relevance. These data suggest that LIP neuronal activation represents saccadic targets and, at a lower level of activity, visual distractors, but does not encode the relevance of distractor stimuli on these tasks.

Animals↗
PubMed1997

Response properties of saccade-related burst neurons in the central mesencephalic reticular formation.

We studied the activity of saccade-related burst neurons in the central mesencephalic reticular formation (cMRF) in awake behaving monkeys. In experiment 1, we examined the activity of single neurons while monkeys performed an average of 225 delayed saccade trials that evoked gaze shifts having horizontal and vertical amplitudes between 2 and 20 degrees . All neurons studied generated high-frequency bursts of activity during some of these saccades. For each neuron, the duration and frequency of these bursts of activity reached maximal values when the monkey made movements within a restricted range of horizontal and vertical amplitudes. The onset of the movement followed the onset of the burst by the longest intervals for movements within a restricted range of horizontal and vertical amplitudes. The range of movements for which this interval was longest varied from neuron to neuron. Across the population, these ranges included nearly all contraversive saccades with horizontal and vertical amplitudes between 2 and 20 degrees. In experiment 2, we used the following task to examine the low-frequency prelude of activity that cMRF neurons generate before bursting: the monkey was required to fixate a light-emitting diode (LED) while two eccentric visual stimuli were presented. After a delay, the color of the fixation LED was changed, identifying one of the two eccentric stimuli as the saccadic target. After a final unpredictable delay, the fixation LED was extinguished and the monkey was reinforced for redirecting gaze to the identified saccadic target. Some cMRF neurons fired at a low frequency during the interval after the fixation LED changed color but before it was extinguished. For many neurons, the firing rate during this interval was related to the metrics of the movement the monkey made at the end of the trial and, to a lesser degree, to the location of the eccentric stimulus to which a movement was not directed.

Animals↗
PubMed1993

Representation of averaging saccades in the superior colliculus of the monkey.

We tested the hypothesis that averaging saccades occur when two different saccades are prepared and executed simultaneously. The activity of saccade-related burst neurons (SRBNs) in the primate superior colliculus was recorded while monkeys made both non-averaging saccades to single targets and averaging saccades which directed the gaze between two simultaneously presented visual targets. For movements of comparable direction and amplitude, the activity measured during averaging and non-averaging saccades was statistically indistinguishable. These results are not consistent with the hypothesis that averaging saccades result from the simultaneous execution of two different saccades at the level of the collicular SRBNs. Instead, these findings indicate that averaging saccades are represented as single intermediate movements within the topographically organized map of these collicular cells.

Animals↗
PubMed1993

Effects of low-frequency stimulation of the superior colliculus on spontaneous and visually guided saccades.

1. The first experiment of this study determined the effects of low-frequency stimulation of the monkey superior colliculus on spontaneous saccades in the dark. Stimulation trains, subthreshold for eliciting short-latency fixed-vector saccades, were highly effective at biasing the metrics (direction and amplitude) of spontaneous movements. During low-frequency stimulation, the distribution of saccade metrics was biased toward the direction and amplitude of movements induced by suprathreshold stimulation of the same collicular location. 2. Low-frequency stimulation biased the distribution of saccade metrics but did not initiate movements. The distribution of intervals between stimulation onset and the onset of the next saccade did not differ significantly from the distribution of intervals between an arbitrary point in time and the onset of the next saccade under unstimulated conditions. 3. Results of our second experiment indicate that low-frequency stimulation also influenced the metrics of visually guided saccades. The magnitude of the stimulation-induced bias increased as stimulation current or frequency was increased. 4. The time course of these effects was analyzed by terminating stimulation immediately before, during, or after visually guided saccades. Stimulation trains terminated at the onset of a movement were as effective as stimulation trains that continued throughout the movement. No effects were observed if stimulation ended 40-60 ms before the movement began. 5. These results show that low-frequency collicular stimulation can influence the direction and amplitude of spontaneous or visually guided saccades without initiating a movement. These data are compatible with the hypothesis that the collicular activity responsible for specifying the horizontal and vertical amplitude of a saccade differs from the type of collicular activity that initiates a saccade.

Animals↗
PubMed1992

Movement selection in advance of action in the superior colliculus.

The primate superior colliculus contains a map of saccadic eye movements. Saccades are high-velocity eye movements to selected targets in the visual field, but little is known about the neural mechanisms responsible for target selection or the related problem of choosing a particular movement from the oculomotor repertoire. Two classes of neurons have been described in the superior colliculus which show bursts of activity before the saccade: discrete bursters display a vigorous pre-saccadic burst and prelude bursters show low-frequency activity as a prelude to burst onset. We have designed experiments to test whether prelude activity is related to saccade selection. Our tasks use a cue to specify which of two physically identical visual stimuli is the goal of an impending saccade. This cue is spatially and temporally isolated from the potential targets as well as from visual cues signalling movement initiation. Our results show that prelude activity occurs shortly after information is available for correct saccade selection and, more importantly, the activity is predictive of saccade choice. The results thus suggest that the superior colliculus participates in the process of saccade selection.

Animals↗
PubMed1987

Neurotensin self-injection in the ventral tegmental area.

Earlier work with the conditioned place-preference paradigm suggested that neurotensin (NT) acts as a behavioral reinforcer when microinjected into the ventral tegmental area (VTA) of the midbrain. We report here that animals will perform an operant task to obtain microinfusions of NT into the VTA. Rats reliably pressed a lever to obtain NT infusions while neglecting an identical but inactive lever. Substitution of saline for NT initiated response extinction; following the reintroduction of NT, reliable responding resumed. These results extend earlier work suggesting that NT in the VTA can be a positive reinforcer.

Animals↗
PubMed1984

Neurotensin: a new 'reward peptide'.

oeurotensin (NT) is a tridecapeptide which is thought to bind to receptors located on dopamine cells in the ventral tegmental area (VTA). Rats with cannulas implanted in the VTA showed a significant increase in time spent in an environment in which they had received bilateral injections of neurotensin on previous days. This is indicative of conditioned reinforcement in which the neuropeptide was the primary reinforcer. In order to determine the specificity of neurotensin receptor interactions, 3 fragments of the peptide were examined at 2 doses. NT1-8 and NT8-13 were found to be inactive while NT1-11 demonstrated significant activity. The results suggest that NT in the VTA is capable of inducing reinforcing effects. This is the first evidence for a non-opiate 'reward peptide'.

Animals↗
PubMed1984

Endogenous opiate reward induced by an enkephalinase inhibitor, thiorphan, injected into the ventral midbrain.

Opiates are known to be reinforcing when injected into the ventral tegmental area (VTA). The present study produced conditioned reinforcement with local injections of exogenous d-ala2-met5-enkephalinamide (DALA), a potent analogue of met-enkephalin, and with thiorphan , an enkephalinase inhibitor which protects endogenous opiates from enzymic degradation. In a conditioned place preference paradigm, rats received injections of DALA (1.0, 3.0, or 8.0 micrograms), thiorphan (60 micrograms), and/or naloxone (10 micrograms), or saline vehicle. Conditioned reinforcement was obtained with 8.0 micrograms of DALA and also with thiorphan but not with thiorphan plus naloxone. This suggests that reward can be generated by endogenous opiates in the VTA. Tests during the light phase and dark phase suggested that diurnal periodicity may play a role in opiate reward. It is concluded that the VTA can generate conditioned reward through transmitter-receptor interaction involving an endogenous opiate substrate which is probably enkephalinergic.

Amino Acids, Sulfur↗