Reinforcement regulates timing variability in thalamus

Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. We identified two opposing factors contributing to timing variability: slow memory fluctuation that degrades performance and reward-dependent exploratory behavior that improves performance. Signatures of these opposing factors were evident across populations of neurons in the dorsomedial frontal cortex (DMFC), DMFC-projecting neurons in the ventrolateral thalamus, and putative target of DMFC in the caudate. However, only in the thalamus were the performance-optimizing regulation of variability aligned to the slow performance-degrading memory fluctuations. These findings reveal how variability caused by exploratory behavior might help to mitigate other undesirable sources of variability and highlight a potential role for thalamocortical projections in this process.

Independent representations of reward-predicting cues and reward history in frontal cortical neurons

SummaryThe transformation of sensory inputs to appropriate goal-directed actions requires estimation of sensory-cue values based on outcome history. To clarify how cortical neurons represent an outcome-predicting cue and actual outcome, we conducted wide-field and two-photon calcium imaging of the mouse neocortex during performance of a classical conditioning task with two cues with different water-reward probabilities. Although licking behavior dominated the area-averaged activity over the whole dorsal neocortex, dorsomedial frontal cortex (dmFrC) affected other dorsal frontal cortical activities, and its inhibition extinguished differences in anticipatory licking between the cues. In individual frontal cortical neurons, the reward-predicting cue was not simultaneously represented with the current or past reward, but licking behavior was frequently multiplexed with the reward-predicting cue and current or past reward. Deep-layer neurons in dmFrC most strongly represented the reward-predicting cue and recent reward history. Our results suggest that these neurons ignite the cortical processes required to select appropriate actions.

Cognitive control of orofacial and vocal responses in the human frontal cortex

The frontal cortical areas critical for human speech production, i.e. the ventrolateral frontal cortex (cytoarchitectonic areas 44 and 45; VLF) and the dorsomedial frontal cortex (DMF) comprising the mid-cingulate cortex (MCC) and the pre-supplementary motor area (preSMA), exist in non-human primates and are implicated in cognitive vocal control functions. The present functional neuroimaging study seeks to define the basic roles of these VLF-DMF network regions in primate vocal production and how they might have been adapted for human speech. We demonstrate that area 44 and the MCC are respectively involved in the cognitive selection of orofacial, non-speech vocal and verbal responses, and the feedback-driven adaptation of these responses – roles that are likely preserved across primates. In contrast, area 45 and preSMA have roles that are specific to human speech: area 45 contributes to active verbal retrieval during learning, while preSMA is involved in processing verbal feedback during orofacial/vocal adaptations.

Hierarchical reasoning by neural circuits in the frontal cortex

Humans process information hierarchically. In the presence of hierarchies, sources of failures are ambiguous. Humans resolve this ambiguity by assessing their confidence after one or more attempts. To understand the neural basis of this reasoning strategy, we recorded from dorsomedial frontal cortex (DMFC) and anterior cingulate cortex (ACC) of monkeys in a task in which negative outcomes were caused either by misjudging the stimulus or by a covert switch between two stimulus-response contingency rules. We found that both areas harbored a representation of evidence supporting a rule switch. Additional perturbation experiments revealed that ACC functioned downstream of DMFC and was directly and specifically involved in inferring covert rule switches. These results‏ reveal the computational principles of hierarchical reasoning, as implemented by cortical circuits.

Neural Mechanisms of Social Cognition in Primates

Activity in a network of areas spanning the superior temporal sulcus, dorsomedial frontal cortex, and anterior cingulate cortex is concerned with how nonhuman primates negotiate the social worlds in which they live. Central aspects of these circuits are retained in humans. Activity in these areas codes for primates’ interactions with one another, their attempts to find out about one another, and their attempts to prevent others from finding out too much about themselves. Moreover, important features of the social world, such as dominance status, cooperation, and competition, modulate activity in these areas. We consider the degree to which activity in these regions is simply encoding an individual's own actions and choices or whether this activity is especially and specifically concerned with social cognition. Recent advances in comparative anatomy and computational modeling may help us to gain deeper insights into the nature and boundaries of primate social cognition.

Flexible sensorimotor computations through rapid reconfiguration of cortical dynamics

SummarySensorimotor computations can be flexibly adjusted according to internal states and contextual inputs. The mechanisms supporting this flexibility are not understood. Here, we tested the utility of a dynamical system perspective to approach this problem. In a dynamical system whose state is determined by interactions among neurons, computations can be rapidly and flexibly reconfigured by controlling the system‘s inputs and initial conditions. To investigate whether the brain employs such control strategies, we recorded from the dorsomedial frontal cortex (DMFC) of monkeys trained to measure time intervals and subsequently produce timed motor responses according to multiple context-specific stimulus-response rules. Analysis of the geometry of neural states revealed a control mechanism that relied on the system‘s inputs and initial conditions. A tonic input specified by the behavioral context adjusted firing rates throughout each trial, while the dynamics in the measurement epoch allowed the system to establish initial conditions for the ensuing production epoch. This initial condition in turn set the speed of neural dynamics in the production epoch allowing the animal to aim for the target interval. These results provide evidence that the language of dynamical systems can be used to parsimoniously link brain activity to sensorimotor computations.

Ventrolateral and dorsomedial frontal cortex lesions impair mnemonic context retrieval

The prefrontal cortex appears to contribute to the mnemonic retrieval of the context within which stimuli are experienced, but only under certain conditions that remain to be clarified. Patients with lesions to the frontal cortex, the temporal lobe and neurologically intact individuals were tested for context memory retrieval when verbal stimuli (words) had been experienced across multiple (unstable context condition) or unique (stable context condition) contexts; basic recognition memory of these words-in-contexts was also tested. Patients with lesions to the right ventrolateral prefrontal cortex (VLPFC) were impaired on context retrieval only when the words had been seen in multiple contexts, demonstrating that this prefrontal region is critical for active retrieval processing necessary to disambiguate memory items embedded across multiple contexts. Patients with lesions to the left dorsomedial prefrontal region were impaired on both context retrieval conditions, regardless of the stability of the stimulus-to-context associations. Conversely, prefrontal lesions sparing the ventrolateral and dorsomedial regions did not impair context retrieval. Only patients with temporal lobe excisions were impaired on basic recognition memory. The results demonstrate a basic contribution of the left dorsomedial frontal region to mnemonic context retrieval, with the VLPFC engaged, selectively, when contextual relations are unstable and require disambiguation.

The Effects of Microstimulation of the Dorsomedial Frontal Cortex on Saccade Latency

Neural regions in the dorsomedial frontal cortex (DMFC), including the supplementary eye field (SEF) and the presupplementary motor area (pre-SMA), are likely candidates for generating top-down control of saccade target selection. To investigate this, we applied electrical microstimulation to these structures while saccades were being planned to visual targets. Stimulation administered to superficial and lateral DMFC sites that were within or close to the SEF delayed ipsilateral and facilitated contralateral saccades. Facilitation was limited to saccades made toward targets in a narrow, contralateral movement field that had endpoints consistent with the goal of evoked saccades. Facilitation occurred with current delivered before target onset and delay with current applied after this time. Stimulation at deeper, medial sites that encompassed the pre-SMA resulted in mostly bilateral delay. The amount of delay at these sites was usually greater for ipsilateral saccades and increased with current amplitude. Changes in saccade latency were not accompanied by altered endpoint, trajectory, or peak velocity. The spatial specificity of SEF stimulation in inducing latency changes suggests that the SEF participates in selecting saccade goals. The less specific delay with pre-SMA stimulation suggests that it is involved in postponing visually guided saccades, thus likely permitting other oculomotor structures to select saccade goals.