Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation.

The dorsal anterior cingulate cortex (dACC) and lateral prefrontal cortex (lPFC) of the non-human primate show neural firing correlations and synchronize at theta and beta frequencies during the monitoring and shifting of attention. These functional interactions might be based on synaptic connectivity that is equally efficacious in both directions, but it might be that there are systematic asymmetries in connectivity consistent with reports of more effective inhibition within the dACC than lPFC, or with a preponderance of dACC projections synapsing onto inhibitory neurons in the lPFC. Here, we tested effective dACC-lPFC connectivity in awake monkeys and report systematic asymmetries in the temporal patterning and latencies of effective connectivity as measured using electrical microstimulation. We found that dACC stimulation-triggered evoked fields (EFPs) were more likely to be multiphasic in the lPFC than in the reverse direction, with a large proportion of connections showing 2-4 inflection points resembling resonance in the 20-30 Hz beta frequency range. Stimulation of dACC → lPFC resulted, on average, in shorter-latency EFPs than lPFC → dACC. Overall, latencies and connectivity strength varied more than twofold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between dACC and lPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We discuss that our results suggest that measuring effective connectivity profiles will be essential for understanding how asymmetries in local synaptic efficacy and connectivity translate into functional neuronal interactions during adaptive, goal-directed behavior.

Task-driven intra- and interarea communications in primate cerebral cortex.

Neural correlations during a cognitive task are central to study brain information processing and computation. However, they have been poorly analyzed due to the difficulty of recording simultaneous single neurons during task performance. In the present work, we quantified neural directional correlations using spike trains that were simultaneously recorded in sensory, premotor, and motor cortical areas of two monkeys during a somatosensory discrimination task. Upon modeling spike trains as binary time series, we used a nonparametric Bayesian method to estimate pairwise directional correlations between many pairs of neurons throughout different stages of the task, namely, perception, working memory, decision making, and motor report. We find that solving the task involves feedforward and feedback correlation paths linking sensory and motor areas during certain task intervals. Specifically, information is communicated by task-driven neural correlations that are significantly delayed across secondary somatosensory cortex, premotor, and motor areas when decision making takes place. Crucially, when sensory comparison is no longer requested for task performance, a major proportion of directional correlations consistently vanish across all cortical areas.

Coherent delta-band oscillations between cortical areas correlate with decision making.

Coherent oscillations in the theta-to-gamma frequency range have been proposed as a mechanism that coordinates neural activity in large-scale cortical networks in sensory, motor, and cognitive tasks. Whether this mechanism also involves coherent oscillations at delta frequencies (1-4 Hz) is not known. Rather, delta oscillations have been associated with slow-wave sleep. Here, we show coherent oscillations in the delta frequency band between parietal and frontal cortices during the decision-making component of a somatosensory discrimination task. Importantly, the magnitude of this delta-band coherence is modulated by the different decision alternatives. Furthermore, during control conditions not requiring decision making, delta-band coherences are typically much reduced. Our work indicates an important role for synchronous activity in the delta frequency band when large-scale, distant cortical networks coordinate their neural activity during decision making.

Coding perceptual discrimination in the somatosensory thalamus.

The sensory thalamus is classically viewed as a relay station of sensory information to cortex, but recent studies suggest that it is sensitive to cognitive demands. There are, however, few experiments designed to test whether this is so. We addressed this problem by analyzing the responses of single neurons recorded in the somatosensory thalamus while trained monkeys reported a decision based on the comparison of two mechanical vibration frequencies applied sequentially to one fingertip. In this task, monkeys must hold the first stimulus frequency (f1) in working memory and compare it to the current sensory stimulus (f2) and must postpone the decision report until a cue triggers the decision motor report, i.e., whether f2 > f1 or f2 < f1. We found that thalamic somatosensory neurons encoded the stimulus frequency either in their periodicity and firing-rate responses, but only during the stimulus periods and not during the working memory and decision components of this task. Furthermore, correlation analysis between behavior and stimulus coding showed that only the firing rate modulations accounted for the overall psychophysical performance. However, these responses did not predict the animal's decision reports on individual trials. Moreover, the sensitivity to changes in stimulus frequency was similar when the monkeys performed the vibrotactile discrimination task and when they were not required to report discrimination. These results suggest that the somatosensory thalamus behaves as a relay station of sensory information to the cortex and that it is insensitive to the cognitive demands of the task used here.

Dynamics of cortical neuronal ensembles transit from decision making to storage for later report.

Decisions based on sensory evaluation during single trials may depend on the collective activity of neurons distributed across brain circuits. Previous studies have deepened our understanding of how the activity of individual neurons relates to the formation of a decision and its storage for later report. However, little is known about how decision-making and decision maintenance processes evolve in single trials. We addressed this problem by studying the activity of simultaneously recorded neurons from different somatosensory and frontal lobe cortices of monkeys performing a vibrotactile discrimination task. We used the hidden Markov model to describe the spatiotemporal pattern of activity in single trials as a sequence of firing rate states. We show that the animal's decision was reliably maintained in frontal lobe activity through a selective state sequence, initiated by an abrupt state transition, during which many neurons changed their activity in a concomitant way, and for which both latency and variability depended on task difficulty. Indeed, transitions were more delayed and more variable for difficult trials compared with easy trials. In contrast, state sequences in somatosensory cortices were weakly decision related, had less variable transitions, and were not affected by the difficulty of the task. In summary, our results suggest that the decision process and its subsequent maintenance are dynamically linked by a cascade of transient events in frontal lobe cortices.

α-Oscillations in the monkey sensorimotor network influence discrimination performance by rhythmical inhibition of neuronal spiking.

Extensive work in humans using magneto- and electroencephalography strongly suggests that decreased oscillatory α-activity (8-14 Hz) facilitates processing in a given region, whereas increased α-activity serves to actively suppress irrelevant or interfering processing. However, little work has been done to understand how α-activity is linked to neuronal firing. Here, we simultaneously recorded local field potentials and spikes from somatosensory, premotor, and motor regions while a trained monkey performed a vibrotactile discrimination task. In the local field potentials we observed strong activity in the α-band, which decreased in the sensorimotor regions during the discrimination task. This α-power decrease predicted better discrimination performance. Furthermore, the α-oscillations demonstrated a rhythmic relation with the spiking, such that firing was highest at the trough of the α-cycle. Firing rates increased with a decrease in α-power. These findings suggest that α-oscillations exercise a strong inhibitory influence on both spike timing and firing rate. Thus, the pulsed inhibition by α-oscillations plays an important functional role in the extended sensorimotor system.

Beta oscillations in the monkey sensorimotor network reflect somatosensory decision making.

The neuronal correlate of perceptual decision making has been extensively studied in the monkey somatosensory system by using a vibrotactile discrimination task, showing that stimulus encoding, retention, and comparison are widely distributed across cortical areas. However, from a network perspective, it is not known what role oscillations play in this task. We recorded local field potentials (LFPs) from diverse cortical areas of the sensorimotor system while one monkey performed the vibrotactile discrimination task. Exclusively during stimulus presentation, a periodic response reflecting the stimulus frequency was observed in the somatosensory regions, suggesting that after initial processing, the frequency content of the stimulus is coded in some other way than entrainment. Interestingly, we found that oscillatory activity in the beta band reflected the dynamics of decision making in the monkey sensorimotor network. During the comparison and decision period, beta activity showed a categorical response that reflected the decision of the monkey and distinguished correct from incorrect responses. Importantly, this differential activity was absent in a control condition that involved the same stimulation and response but no decision making required, suggesting it does not merely reflect the maintenance of a motor plan. We conclude that beta band oscillations reflect the temporal and spatial dynamics of the accumulation and processing of evidence in the sensorimotor network leading to the decision outcome.

Decoding a perceptual decision process across cortex.

Perceptual decisions arise from the activity of neurons distributed across brain circuits. But, decoding the mechanisms behind this cognitive operation across brain circuits has long posed a difficult problem. We recorded the neuronal activity of diverse cortical areas, while monkeys performed a vibrotactile discrimination task. We find that the encoding of the stimuli during the stimulus periods, working memory, and comparison periods is widely distributed across cortical areas. Notably, during the comparison and postponed decision report periods the activity of frontal brain circuits encode both the result of the sensory evaluation that corresponds to the monkey's possible choices and past information on which the decision is based. These results suggest that frontal lobe circuits are more engaged in the readout of sensory information from working memory, when it is required to be compared with other sensory inputs, than simply engaged in motor responses during this task.

Procedure for recording the simultaneous activity of single neurons distributed across cortical areas during sensory discrimination.

We report a procedure for recording the simultaneous activity of single neurons distributed across five cortical areas in behaving monkeys. The procedure consists of a commercially available microdrive adapted to a commercially available neural data collection system. The critical advantage of this procedure is that, in each cortical area, a configuration of seven microelectrodes spaced 250-500 mum can be inserted transdurally and each can be moved independently in the z axis. For each microelectrode, the data collection system can record the activity of up to five neurons together with the local field potential (LFP). With this procedure, we normally monitor the simultaneous activity of 70-100 neurons while trained monkeys discriminate the difference in frequency between two vibrotactile stimuli. Approximately 20-60 of these neurons have response properties previously reported in this task. The neuronal recordings show good signal-to-noise ratio, are remarkably stable along a 1-day session, and allow testing several protocols. Microelectrodes are removed from the brain after a 1-day recording session, but are reinserted again the next day by using the same or different x-y microelectrode array configurations. The fact that microelectrodes can be moved in the z axis during the recording session and that the x-y configuration can be changed from day to day maximizes the probability of studying simultaneous interactions, both local and across distant cortical areas, between neurons associated with the different components of this task.

Neural correlates of a postponed decision report.

Depending on environmental demands, a decision based on a sensory evaluation may be either immediately reported or postponed for later report. If postponed, the decision must be held in memory. But what exactly is stored by the underlying memory circuits, the final decision itself or the sensory information that led to it? Here, we report that, during a postponed decision report period, the activity of medial premotor cortex neurons encodes both the result of the sensory evaluation that corresponds to the monkey's possible choices and past sensory information on which the decision is based. These responses could switch back and forth with remarkable flexibility across the postponed decision report period. Moreover, these responses covaried with the animal's decision report. We propose that maintaining in working memory the original stimulus information on which the decision is based could serve to continuously update the postponed decision report in this task.

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.

Decoding the temporal evolution of a simple perceptual act.

Most perceptual tasks require sequential steps to be carried out. This must be the case, for example, when subjects discriminate the difference in frequency between two mechanical vibrations applied sequentially to their fingertips. This perceptual task can be understood as a chain of neural operations: encoding the two consecutive stimulus frequencies, maintaining the first stimulus in working memory, comparing the second stimulus to the memory trace left by the first stimulus, and communicating the result of the comparison to the motor apparatus. Where and how in the brain are these cognitive operations executed? We addressed this problem by recording single neurons from several cortical areas while trained monkeys executed the vibrotactile discrimination task. We found that primary somatosensory cortex (S1) drives higher cortical areas where past and current sensory information are combined, such that a comparison of the two evolves into a decision. Consistent with this result, direct activation of the S1 can trigger quantifiable percepts in this task. These findings provide a fairly complete panorama of the neural dynamics that underlies the transformation of sensory information into an action and emphasize the importance of studying multiple cortical areas during the same behavioural task.

Bootstrap-based methods for testing factor-by-curve interactions in generalized additive models: assessing prefrontal cortex neural activity related to decision-making.

In many situations the effect of a continuous covariate on response varies across groups defined by levels of a categorical variable. This paper addresses generalized additive models incorporating the so-called factor-by-curve interaction. A local scoring algorithm based on local linear kernel smoothers was used to estimate the model. Two different types of bootstrap-based procedures are proposed for testing interaction terms, namely, the likelihood ratio test, and a procedure based on an estimate of the interaction terms. Given the high computational cost involved, binning techniques were used to speed up computation in the estimation and testing processes. A simulation study was conducted to assess the validity of these bootstrap-based tests. This methodology was applied to studying prefrontal cortex neural activity associated with decision-making in monkeys. The proposed statistical procedure proved very useful in revealing the neural activity correlates of decision-making strategies adopted by monkeys in accordance with different behavioural tasks.