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Biomedical subjects

S P Wise

Publications and source records attributed to S P Wise.

At least 19 recordsLinked to original sources
PubMed2003

Role of the hippocampal system in associative learning beyond the spatial domain.

Expert opinion remains divided on the issue of whether the hippocampal system functions exclusively in spatial information processing, e.g. in navigation or in understanding spatial relations, or whether it plays a more general role in higher brain function. Previous work on monkeys and rats has tended to support the former view, whereas observations in the clinic point to the latter, including functions as diverse as declarative knowledge, episodic memory, word learning, and understanding relations among objects. One influential theory posits a general role for the hippocampal system in associative learning, with emphasis on associations learned rapidly and recently. The results presented here are consistent with this theory, along with previous clinical and theoretical studies indicating that the hippocampal system is necessary for associative learning even if no component of the association relies on spatial information. In the study reported here, rhesus monkeys learned a series of conditional stimulus-response associations involving complex visual stimuli presented on a video monitor. Each stimulus instructed one of three responses: tapping the stimulus with the hand, steady hand contact with the stimulus for a brief period of time, or steady contact for a longer time. Fornix transection impaired the learning of these associations, even though both the stimuli and the responses were nonspatially differentiated, and this deficit persisted for at least 2 years. This finding indicates that the hippocampal system plays an important role in associative learning regardless of the relevance of spatial information to any aspect of the association. Fornix-transected monkeys were impaired in learning new stimulus-response associations even when the stimuli were highly familiar. Thus, the deficit was one of associating each stimulus with a response, as opposed to problems in distinguishing the stimuli from each other. In contrast to these effects, fornix transection did not impair performance when familiar stimuli instructed a response according to an already-learned association, which shows that the deficit was one of learning new associations rather than one of retention or retrieval of previously learned ones. Taken together, these results show that fornix transection causes a long-lasting impairment in associative learning outside of the spatial domain, in a manner consistent with theories of hippocampal-system function that stress a general role in the rapid acquisition of associative knowledge.

Animals↗
PubMed2001

A novel food-delivery device for neurophysiological and neuropsychological studies in monkeys.

Neurophysiological and neuropsychological studies in monkeys sometimes require an automated food-pellet dispenser. Commercially available dispensers typically sequester the pellet until delivery and, once delivered, the pellet's availability cannot be controlled. The custom-designed dispenser described here overcomes those two limitations. The device is composed of two separate units: a feeder and an electronic controller. The feeder manipulates food pellets with actuators driven by air pressure and delivers them into a serving bowl. The controller's settings determine whether the monkey can retrieve a pellet from the bowl. If the experiment requires that the pellet be visible and within reach, but unavailable for retrieval, the controller enables a trap-door mechanism at the bottom of the bowl. Any motion near the serving bowl, such as that caused by the approach of a monkey's hand, will then trigger the opening of the trap door, which causes the pellet to fall into an enclosed pellet collector. This rapid pellet-removal mechanism can also be triggered by other computer-controlled contingencies. Two of these dispensers have been in operation in an applied laboratory setting for over 2 years.

Algorithms↗
PubMed2001

Neuronal activity in dorsomedial frontal cortex and prefrontal cortex reflecting irrelevant stimulus dimensions.

Previous studies of the dorsomedial frontal cortex (DMF) and the prefrontal cortex (PF) have shown that, when monkeys respond to nonspatial features of a discriminative stimulus (e.g., color) and the stimulus appears at a place unrelated to the movement target, neurons nevertheless encode stimulus location. This observation could support the idea that these neurons always encode stimulus location, regardless of its relevance to an instrumentally conditioned behavior. Past studies, however, leave open the possibility that activity observed during one operant task might reflect the contingencies of a different task, performed at different times. To test these alternatives, we examined the activity of DMF and PF neurons in two rhesus monkeys conditioned to perform an operant eye-movement task in which only the color and shape of visual stimuli served as salient discriminative features. Each of eight stimuli was associated with a response to a different eye-movement target. The location of these stimuli varied from trial to trial but was of no behavioral relevance, and the monkeys did not perform any operant task in which stimulus location controlled behavior. A substantial minority of neurons in both DMF and PF nevertheless encoded stimulus location, which indicates that this property does not depend on its relevance in an instrumentally conditioned behavior.

Action Potentials↗
PubMed2001

The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta).

Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less, within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions. Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex, but rapid, within-session learning does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift, which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session, and reducing the working memory load did not improve within-session learning.

Animals↗
PubMed2001

Tuning for the orientation of spatial attention in dorsal premotor cortex.

We tested whether neuronal activity in the dorsal premotor cortex (PMd) reflected the orientation of selective spatial attention, as opposed to the target of a reaching movement, eye position and saccade direction. These four spatial variables were dissociated in two tasks, which both required that a monkey attend to a robot's location in order to know when to make a movement. However, the target of the reaching movement varied; it was the robot's location in one task, but a different location in the other task. Eye position was recorded, but not explicitly controlled. Of 199 PMd neurons sampled, 19% had activity related to eye position, and an overlapping 11% were related to saccade direction (totaling 24% of the PMd sample). Of the 152 PMd neurons that lacked oculomotor relationships, approximately 20% reflected the orientation of selective spatial attention. Attentional tuning may account, at least in part, for gaze-independent receptive fields and visuospatial, target or goal relationships in tasks involving stimulus-response incompatibility.

Animals↗
PubMed2001

Prefrontal cortex neurons reflecting reports of a visual illusion.

When a small, focally attended visual stimulus and a larger background frame shift location at the same time, the frame's new location can affect spatial perception. For horizontal displacements on the order of 1--2 degrees, when the frame moves more than the attended stimulus, human subjects may perceive that the attended stimulus has shifted to the right or left when it has not done so. However, that misapprehension does not disable accurate eye movements to the same stimulus. We trained a rhesus monkey to report the direction that an attended stimulus had shifted by making an eye movement to one of the two report targets. Then, using conditions that induce displacement illusions in human subjects, we tested the hypothesis that neuronal activity in the prefrontal cortex (PF) would reflect the displacement directions reported by the monkey, even when they conflicted with the actual displacement, if any, of the attended stimulus. We also predicted that these cells would have directional selectivity for movements used to make those reports, but not for similar eye movements made to fixate the attended stimulus. A population of PF neurons showed the predicted properties, which could not be accounted for on the basis of either eye-movement or frame-shift parameters. This activity, termed report-related, began approximately 150 ms before the onset of the reporting saccade. Another population of PF neurons showed greater directional selectivity for saccadic eye movements made to fixate the attended stimulus than for similar saccades made to report its displacement. In view of the evidence that PF functions to integrate inputs and actions occurring at different times and places, the present findings support the idea that such integration involves movements to acquire response targets, directly, as well as actions guided by less direct response rules, such as perceptual reports.

Animals↗
PubMed2000

Mechanisms of use-dependent plasticity in the human motor cortex.

Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-d-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-d-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation.

Dextromethorphan↗
PubMed2000

Role of prefrontal cortex in a network for arbitrary visuomotor mapping.

In arbitrary visuomotor mapping, an object instructs a particular action or target of action, but does so in a particular way. In other forms of visuomotor control, the object is either the target of action (termed standard mapping) or its location provides the information needed for targeting (termed transformational mapping). By contrast, in arbitrary mapping, the object's location bears no systematic spatial relationship with the action. Neuropsychological and neurophysiological investigation has, in large part, identified the neural network that underlies the rapid acquisition and performance of arbitrary visuomotor mappings. This network consists of parts of the premotor (PM) and prefrontal (PF) cortex, the hippocampal system (HS), and the basal ganglia (BG). Here, we propose specialized contributions of the network's different components to its overall function. To do so, we invoke the concept of distributed information-processing architectures, or modules, which may involve a variety of neural structures. According to this view, recurrent neural networks involving cortex, basal ganglia, and thalamus operate largely in parallel. Each of these interacting networks can be termed a cortical-BG module. A large number of these modules include PM neurons, and they can be termed PM cortical-BG modules. A comparable number include PF neurons, termed PF cortical-BG modules. We propose that PM and PF cortical-BG modules compute specific object-to-action mappings, in which the network learns the action associated with a given input. These mappings serve as specific solutions to arbitrary visuomotor mapping problems. However, they are also exemplars of more abstract rules, such as the knowledge that nonspatial visual information (e.g., color) can guide the choice of action. We propose that PF cortical-BG modules subserve abstract rules of this kind, along with other problem-solving strategies. This view should not be taken to imply that the PF network lacks the capacity to compute specific mappings, but rather that it has higher-order mapping functions in addition to its lower-order ones. Furthermore, it seems likely that PF provides PM with pertinent sensory information. The hippocampal system appears to play a role parallel to that of both neocortical-BG networks discussed here. However, in accord with several models, it operates mainly in the intermediate term, pending the consolidation of the relevant information in those neocortical-BG networks.

Animals↗
PubMed2000

Oscillations in the premotor cortex: single-unit activity from awake, behaving monkeys.

We examined single-unit activity in the dorsal premotor cortex for evidence of fast neuronal oscillations. Four rhesus monkeys performed a task in which visuospatial instruction stimuli indicated the direction of forelimb movement to be executed on each trial. After an instructed delay period of 1.5-3 s, movements to either the right or left of a central origin were triggered by a second visuospatial stimulus. From a database of 579 single units, 78 units (13%) contained periodic peaks in their autocorrelation histograms (ACHs), with oscillation frequencies typically 20-30 Hz (mean 27 Hz). An additional 26 units (5%) had oscillatory features that were identified in joint interspike-interval (ISI) plots. Three observations, taken together, suggest entrainment by rhythmic drive extrinsic to these neurons: shuffling ISIs attenuated ACH peaks, indicating a dependency on serial-order effects; oscillation frequency did not change during either increases or decreases in firing rate; and joint ISI plots contained features consistent with a rhythmicity interrupted by intervening discharges. In some cells, oscillations occurred for only one of the two directions of movement. During the delay period, such directional selectivity was observed in 37 units (60% of delay-period oscillators). For at least 17 of these units, we could exclude the possibility that oscillatory directional selectivity resulted from the difficulty in detecting oscillations due to low discharge rates (for one of the two movement directions). Directional selectivity in fast oscillations shows that they can reflect specific aspects of an intended action.

Animals↗
PubMed2000

Arbitrary associations between antecedents and actions.

The arbitrary linkage of sensory cues to actions and goals represents one of the most-flexible capabilities in the behavioral repertoire of mammals. This ability has been termed 'conditional motor learning', 'conditional discrimination' or, more recently, 'arbitrary visuomotor mapping'. Unlike other forms of visuomotor guidance, in arbitrary mapping the location of the sensory cue lacks any systematic spatial relationship with the action or its goal. Recent work has identified much of the neural network that underlies this behavior. It consists of parts of the frontal cortex, hippocampal system and basal ganglia, each of which has neurons whose activity undergoes systematic evolution during learning.

Animals↗
PubMed2000

A model that accounts for activity prior to sensory inputs and responses during matching-to-sample tasks.

Neural network models were examined during delayed matching-to-sample tasks (DMS), and neurons in a monkey's prefrontal cortex were studied during the performance of comparable tasks. In DMS, various input stimuli follow a sample stimulus, and an output should occur whenever the sample reappears. Our previous models have been restricted to certain kinds of inputs, outputs, and temporal patterns. Here, we generalized the models by training them on both spatial and nonspatial inputs, spatial and nonspatial outputs, and both fixed and variable interstimulus intervals. Two versions of DMS were presented to both the model and the monkey, both involving nonspatial samples: (1) Two stimuli simultaneously appeared at a variable interval after the sample; and (2) A series of single stimuli appeared at fixed intervals after the sample. Both versions required identical spatial responses, reflecting the direction (left or right) of the matching stimulus relative to a central origin. Thus, these two versions of DMS involved the same samples, memory, and responses, but established different response contexts. Our analysis focused on unit activity prior to stimuli, as well as that prior to responses, termed anticipatory and response-related activity, respectively. In both the model and the monkey, anticipatory activity occurred only for fixed interstimulus intervals. In the model, we could determine that anticipatory activity acted either like a filter to suppress inappropriate responses or it served to enhance the network's general readiness to respond. As for response-related activity, units in both the model and the monkey showed directional selectivity and had a strong dependence on response context. In the model, we could show that this activity contributed both to the suppression of inappropriate responses and to the generation of correct ones. None of the model's hidden units contributed exclusively to computing the direction of match output. Instead, their response-related activity contributed to the computation of both the match decision and the correct response direction.

Animals↗
PubMed1999

Role of the hippocampal system in conditional motor learning: mapping antecedents to action.

Macaque monkeys can learn arbitrary mappings between stimuli and spatially directed actions (often termed conditional motor learning), and, after the development of a strong learning set, can do so in just a few trials. Ablation studies have shown that the hippocampus plus subjacent cortex is necessary for this rapid and highly flexible type of learning. We consider evidence that the arbitrary mapping function of the hippocampal system may be more general and fundamental than currently accepted and what limitations there may be, if any, on the information that it can map. Removal of the hippocampal system yields a pattern of deficits and preserved abilities that correlates remarkably closely with that found in human global amnesics, such as patient H.M., on a variety of declarative memory tasks. Thus, the rapid acquisition of arbitrary visuomotor mappings may represent an example of declarative memory in nonhuman primates.

Animals↗
PubMed1999

Rule-dependent neuronal activity in the prefrontal cortex.

We studied single-neuron activity in the prefrontal cortex (PF) while a monkey performed a task according to two different rules, termed conditional and spatial. The monkey viewed a video screen, and its task required a hand movement in response to the dimming of a light spot. There were four light spots on the screen: right, left, up, and down from the center. Only one of the four spots dimmed, and the degree of dimming was slight. Accordingly, the monkey needed to foveate the "correct" light spot to detect the dimming. A visual cue indicated which of the four light spots would be deemed correct and, thus, would dim on each trial. The sequence of events was as follows: a fixation spot appeared at the center of the screen; then, a cue appeared twice at one of the four potential target locations; then, the four target spots appeared; and, finally, one of them dimmed. Except for the color of an initial fixation point, the cues, their locations, and other events were identical for the conditional and spatial rules. The rules differed in one essential way. For the conditional rule, nonspatial attributes of the visual cue indicated which of the four light spots would dim, and the cue's location was irrelevant. For the spatial rule, the cue's location determined the correct target on that trial. The light spot at the location of the cue always dimmed, regardless of which cue appeared there. Our sample included 221 PF neurons showing significant task-related activity modulation, distributed among dorsal, dorsolateral, and ventral PF regions. Between one-third and one-half of the sample in each of those regions showed statistically significant activity differences that could be attributed to the rule. Selectivity for cues and/or their locations was common. However, there was no significant regional segregation of such selectivity. These data support the hypothesis that PF plays a role in the guidance of behavior according to previously learned rules.

Animals↗
PubMed1998

A model that accounts for activity in primate frontal cortex during a delayed matching-to-sample task.

A fully recurrent neural network model was optimized to perform a spatial delayed matching-to-sample task (DMS). In DMS, a stimulus is presented at a sample location, and a match is reported when a subsequent stimulus appears at that location. Stimuli elsewhere are ignored. Computationally, a DMS system could consist of memory and comparison components. The model, although not constrained to do so, worked by using two corresponding classes of neurons in the hidden layer: storage and comparator units. Storage units form a dynamical system with one fixed point attractor for each sample location. Comparator units constitute a system receiving input from these storage units as well as from current input stimuli. Both unit types were tuned directionally. These two sources of information combine to create unique patterns of activity that determine whether a match has occurred. In networks with abundant hidden units, the storage and comparator functions were distributed so that individual units took part in both. We compared the model with single-neuron recordings from premotor (PM) and prefrontal (PF) cortex. As shown previously, many PM and PF neurons behaved like storage units. In addition, both regions contain neurons that behave like the comparator units of the model and appear to have dual functionality similar to that observed in the model units. No neuron in either area had properties identical to those of the match output neuron of the model. However, four PF neurons and one PM neuron resembled the output signal more closely than any of the hidden units of the model.

Animals↗
PubMed1998

Changes in motor cortical activity during visuomotor adaptation.

We examined neuronal activity in three motor cortical areas while a rhesus monkey adapted to novel visuomotor transforms. The monkey moved a joystick that controlled a cursor on a video screen. Each trial began with the joystick centered. Next, the cursor appeared in one of eight positions, arranged in a circle around a target stimulus at the center of the screen. To receive reinforcement, the monkey moved the joystick so that the cursor contacted the target continuously for Is. The video monitor provided continuous visual feedback of both cursor and target position. With those elements of the task constant, we modified the transform between joystick movement and that of the cursor at the beginning of a block of trials. Neuronal activity was studied as the monkey adapted to these novel joystick-cursor transforms. Some novel tasks included spatial transforms such as single-axis inversions, asymmetric double-axis inversions and angular deviations (also known as rotations). Other tasks involved changes in the spatiotemporal pattern and magnitude of joystick movement. As the monkey adapted to various visuomotor tasks, 209 task-related neurons (selected for stable background activity) showed significant changes in their task-related activity: 88 neurons in the primary motor cortex (M1), 32 in the supplementary motor cortex (M2), and 89 in the caudal part of the dorsal premotor cortex (PMdc). Slightly more than half of the sample in each area showed significant changes in the magnitude of activity modulation during adaptation, with the number of increases approximately equaling the number of decreases. These data support the prediction that changes in task-related neuronal activity can be observed in M1 during motor adaptation, but fail to support the hypothesis that M1 and PMdc differ in this regard. When viewed in population averages, motor cortex continued to change its activity for at least dozens of trials after performance reached a plateau. This slow, apparently continuing change in the pattern and magnitude of task-related activity may reflect the initial phases of consolidating the motor memory for preparing and executing visuomotor skills.

Adaptation, Physiological↗
PubMed1998

Cortical areas with enhanced activation during object-centred spatial information processing. A PET study.

The phenomenon of object-centred unilateral neglect suggests that some neural networks process spatial information relative to reference objects. To examine object-centred information processing, we measured regional cerebral blood flow in 11 normal subjects with PET. During each PET scan, a subject viewed a sample stimulus followed by a cue on a video screen. The sample consisted of two polygons, termed 'objects', each located in a corner of the screen. A small target spot appeared in a corner of each polygon. There were two tasks: the visuomotor task and the matching-to-sample task. In the visuomotor task, the subject moved a joystick in a direction indicated by either the location of the target spot inside the object (if object-centred coordinates were operative) or the location of the object relative to the video screen (if screen-centred coordinates were operative). In the matching-to-sample task, the subject moved the joystick to report whether the relevant spatial information (object- or screen-centred) in the cue matched the sample. In both the visuomotor and the matching-to-sample task, use of object-centred (versus screen- or viewer-centred) information caused augmented activation in the inferior occipitotemporal cortex, bilaterally, in the left superior occipital gyrus, and in both the thalamus and the brainstem. In addition, in the visuomotor task such activation occurred in the right posterior parietal cortex and in the left ventral premotor, dorsolateral prefrontal and anterior supplementary motor areas. These findings suggest the involvement of the occipitotemporal cortex and a broad frontoparietal network when, as in the visuomotor task, object-centred information guides movement. When the same data underlie declarative reports, as in the matching-to-sample task, the occipitotemporal cortex remains engaged but the frontoparietal network diminishes in importance.

Adolescent↗
PubMed1998

Rapid plasticity of human cortical movement representation induced by practice.

The process of acquiring motor skills through the sustained performance of complex movements is associated with neural plasticity. However, it is unknown whether even simple movements, repeated over a short period of time, are effective in inducing cortical representational changes. Whether the motor cortex can retain specific kinematic aspects of a recently practiced movement is also unknown. We used focal transcranial magnetic stimulation (TMS) of the motor cortex to evoke isolated and directionally consistent thumb movements. Thumb movements then were practiced in a different direction. Subsequently, TMS came to evoke movements in or near the recently practiced direction for several minutes before returning to the original direction. To initiate a change of the TMS-evoked movement direction, 15 or 30 min of continuous training were required in most of the subjects and, on two occasions, as little as 5 or 10 min. Substantially smaller effects followed more direct stimulation of corticofugal axons with transcranial electrical stimulation, pointing to cortex as the site of plasticity. These findings suggest that the training rapidly, and transiently, established a change in the cortical network representing the thumb, which encoded kinematic details of the practiced movement. This phenomenon may be regarded as a short-term memory for movement and be the first step of skill acquisition.

Adult↗