Carlos Acuña

The primate pulvinar nuclei: vision and action

The pulvinar nuclei of the thalamus are proportionately larger in higher mammals, particularly in primates, and account for a quarter of the total mass. Traditionally, these nuclei have been divided into oral (somatosensory), superior and inferior (both visual) and medial (visual, multi-sensory) divisions. With reciprocal connections to vast areas of cerebral cortex, and input from the colliculus and retina, they occupy an analogous position in the extra-striate visual system to the lateral geniculate nucleus in the primary visual pathway, but deal with higher-order visual and visuomotor transduction. With a renewed recent interest in this thalamic nuclear collection, and growth in our knowledge of the cortex with which it communicates, perhaps the time is right to look to new dimensions in the pulvinar code.

Neural Correlates of Decisions and Their Outcomes in the Ventral Premotor Cortex

Selection of the appropriate action in a changing environment involves a chain of events that goes from perception through decision to action and evaluation of the outcomes. What and where in the brain are the correlates of these events? The ventral premotor cortex (PMv) is a candidate because (1) it is involved in sensory transformations for visually guided actions and in perceptual decisions, and (2) it is connected with sensory, motor, and high-level cognitive areas related to performance monitoring. Therefore, we hypothesized that it would be the site for representing sensory perception for action and for evaluating the decision consequences. Trained monkeys were required to discriminate the orientation of two lines showed in sequence and separated by a delay. Monkeys compared the orientation of the second line with the memory trace of the first and communicated whether the second was to the left or to the right of the first. Here we show that the activity of PMv neurons reflected (1) the first stimuli and its memory trace during the delay and comparison periods, (2) its comparison with the second stimuli, including the strength of the evidence, and (3) the result of the discrimination (choice). After the monkeys reported the choice, there were neurons that only encoded the choices, others only the outcomes, and others the choices and outcomes together. The representation of task cues, decision variables, and their outcomes suggest a role of PMv as part of a supervisory network involved in shaping future behavior and in learning.

Further observations on the role of nitric oxide in the feline lateral geniculate nucleus

We have examined the responses of a population of 77 cells in the dorsal lateral geniculate nucleus (dLGN) of the anaesthetized, paralysed cat. Here the synthetic enzyme for the production of nitric oxide, nitric oxide synthase, is found only in the presynaptic terminals of the cholinergic input from the brainstem. In our hands, iontophoretic application of inhibitors of this enzyme resulted both in significant decreases in visual responses and decreased responses to exogenous application of NMDA, effects which were reversed by coapplication of the natural substrate for nitric oxide synthase, L‐arginine, but not the biologically inactive isomer, D‐arginine. Nitroprusside and S‐nitroso‐N‐acetylpenicillamine (SNAP), nitric oxide donors, but not L‐arginine, were able to increase markedly both spontaneous activity and the responsiveness to NMDA application. Furthermore, SNAP application facilitated visual responses. Responses of cells in animals without retinal, cortical and parabrachial input to the LGN suggest a postsynaptic site of action of nitric oxide. This modulation of the gain of visual signals transmitted to the cortex suggests a completely novel pathway for nitric oxide regulation of function, as yet described only in primary sensory thalamus of the mammalian central nervous system.

Actions of compounds manipulating the nitric oxide system in the cat primary visual cortex

1 We iontophoretically applied NG‐nitro‐L‐arginine (l‐NOArg), an inhibitor of nitric oxide synthase (NOS), to cells (n= 77) in area 17 of anaesthetized and paralysed cats while recording single‐unit activity extracellularly. In twenty‐nine out of seventy‐seven cells (38%), compounds altering NO levels affected visual responses. 2 In twenty‐five out of twenty‐nine cells, l‐NOArg non‐selectively reduced visually elicited responses and spontaneous activity. These effects were reversed by co‐application of l‐arginine (l‐Arg), which was without effect when applied alone. Application of the NO donor diethylamine‐nitric oxide (DEA‐NO) produced excitation in three out of eleven cells, all three cells showing suppression by l‐NOArg. In ten cells the effect of the soluble analogue of cGMP, 8‐bromo‐cGMP, was tested. In three of those in which l‐NOArg application reduced firing, 8‐bromo‐cGMP had an excitatory effect. In six out of fifteen cells tested, L‐NOArg non‐selectively reduced responses to NMDA and α‐amino‐3‐hydroxy‐5‐methylisoxasole‐4‐propionic acid (AMPA). Again, co‐application of l‐Arg reversed this effect, without enhancing activity beyond control values. 3 In a further subpopulation of ten cells, l‐NOArg decreased responses to ACh in five. 4 In four out of twenty‐nine cells l‐NOArg produced the opposite effect and increased visual responses. This was reversed by co‐application of l‐Arg. Some cells were also affected by 8‐bromo‐cGMP and DEA‐NO in ways opposite to those described above. It is possible that the variety of effects seen here could also reflect trans‐synaptic activation, or changes in local circuit activity. However, the most parsimonious explanation for our data is that NO differentially affects the activity of two populations of cortical cells, in the main causing a non‐specific excitation.

A role for the ventral premotor cortex beyond performance monitoring

Depending on the circumstances, decision making requires either comparing current sensory information with that showed recently or with that recovered from long-term memory (LTM). In both cases, to learn from past decisions and adapt future ones, memories and outcomes have to be available after the report of a decision. The ventral premotor cortex (PMv) is a good candidate for integrating memory traces and outcomes because it is involved in working-memory, decision-making, and encoding the outcomes. To test this hypothesis we recorded the extracellular unit activity while monkeys performed 2 variants of a visual discrimination task. In one task, the decision was based on the comparison of the orientation of a current stimulus with that of another stimulus recently shown. In the other task, the monkeys had to compare the current orientation of the stimulus with the correct one retrieved from LTM. Here, we report that when the task required retrieval of the stimulus and its use in the following trials, the neurons continue encoding this internal representation together with the outcomes after the monkey has emitted the motor response. However, this codification did not occur when the stimulus was shown recently and updated every trial. These results suggest that the PMv activity represents the information needed to evaluate the consequences of a decision. We interpret these results as evidence that the PMv plays a role in evaluating the outcomes that can serve to learn and thus adapt future decision to environmental demands.

Neural correlates of memory retrieval in the prefrontal cortex.

Working memory includes short‐term representations of information that were recently experienced or retrieved from long‐term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long‐term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters − the orientation − of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short‐term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.

A Flexible Method to Measure Synchrony in Neuronal Firing

Neurons can transmit information about the characteristics of a stimulus through the spike rate of neurons and synchronization of the neurons. Various association measure can be used to describe how “synchronous” two spike trains are. We propose a new measure of synchrony, the conditional synchrony measure, which is the probability of firing together given that at least one of the two neurons is active. Focus is on the specification of a flexible marginal model for multivariate correlated binary data together with a pseudolikelihood estimation approach, to adequately and directly describe the measures of interest. A joint model must allow different time- and covariate-dependent firing rates for each neuron, and also must account for the association between them. The association between neurons might depend on covariates as well.

Decision-Making, Behavioral Supervision and Learning: An Executive Role for the Ventral Premotor Cortex?

In order to adjust the behavioral performance in a changing environment, subjects have to monitor their evolving actions and to know whether their responses were correct or incorrect. This requires self-awareness, cognitive flexibility, working memory (WM), and decision making that frequently are impaired in psychosis. What is the neural substrate of these processes and where are these substrates located? Dysfunction of prefrontal, parietal, temporal cortices, and associated subcortical structures are known to be involved in some of these symptoms. The prefrontal–subcortical circuits have been the main focus of study while other cortical areas such as the premotor cortex have received less attention. The main focus of this review is about the evidence that the ventral premotor cortex processes both recent sensory information and that from long-term memory to decide and evaluate the behavior of previous decisions. This process may serve for learning and thus adapting future behavior to environmental demands. Therefore, dysfunction of this cortical area could be related to some cognitive neuropsychiatric disorders.

Decision-Making in the Ventral Premotor Cortex Harbinger of Action

Although the premotor (PM) cortex was once viewed as the substrate of pure motor functions, soon it was realized that it was involved in higher brain functions. By this it is meant that the PM cortex functions would better be explained as motor set, preparation for limb movement, or sensory guidance of movement rather than solely by a fixed link to motor performance. These findings, together with a better knowledge of the PM cortex histology and hodology in human and non-human primates prompted quantitative studies of this area combining behavioral tasks with electrophysiological recordings. In addition, the exploration of the PM cortex neurons with qualitative methods also suggested its participation in higher functions. Behavioral choices frequently depend on temporal cues, which together with knowledge of previous outcomes and expectancies are combined to decide and choose a behavioral action. In decision-making the knowledge about the consequences of decisions, either correct or incorrect, is fundamental because they can be used to adapt future behavior. The neuronal correlates of a decision process have been described in several cortical areas of primates. Among them, there is evidence that the monkey ventral premotor (PMv) cortex, an anatomical and physiological well-differentiated area of the PM cortex, supports both perceptual decisions and performance monitoring. Here we review the evidence that the steps in a decision-making process are encoded in the firing rate of the PMv neurons. This provides compelling evidence suggesting that the PMv is involved in the use of recent and long-term sensory memory to decide, execute, and evaluate the outcomes of the subjects’ choices.

Ventral premotor cortex neuronal activity matches perceptual decisions

The relationship between neuronal activity and psychophysical judgments is central to understanding the brain mechanisms responsible for perceptual decisions. The ventral premotor cortex is known to be involved in representing different components of the decision‐making process. In this cortical area, however, neither the neuronal ability to discriminate nor the trial‐to‐trial relationship between neuronal activity and behavior have been studied during visual decision‐making. We recorded from single neurons while monkeys reported a decision based on the comparison of the orientation of two lines shown sequentially and separated by a delay. Analyses based on signal detection theory provided both the behavioral and neuronal sensitivities (d′) and the coherence between behavioral and neuronal choices. To determine the temporal evolution of neuronal sensitivity and of coherence, the optimal size and position of the encoding windows were assessed. For a subset of neurons from the premotor ventral cortex, neuronal sensitivity was close to behavioral sensitivity and the trial‐to‐trial coherence between the neuronal and behavioral choices was close to 100%. By comparing these results with those obtained in a motor control task we ruled out the possibility of this activity being explained by the motor component of the task. These results suggest that activity in the ventral premotor cortex explains behavioral performance and predicts trial‐to‐trial subject choices.