Behaviors are influenced by rewards to both oneself and others, but the neurons and neural connections that monitor and evaluate rewards in social contexts are unknown. To address this issue, we devised a social Pavlovian conditioning procedure for pairs of monkeys. Despite being constant in amount and probability, the subjective value of forthcoming self-rewards, as indexed by licking and choice behaviors, decreased as partner-reward probability increased. This value modulation was absent when the conspecific partner was replaced by a physical object. Medial prefrontal cortex neurons selectively monitored self-reward and partner-reward information, whereas midbrain dopaminergic neurons integrated this information into a subjective value. Recordings of local field potentials revealed that responses to reward-predictive stimuli in medial prefrontal cortex started before those in dopaminergic midbrain nuclei and that neural information flowed predominantly in a medial prefrontal cortex-to-midbrain direction. These findings delineate a dedicated pathway for subjective reward evaluation in social environments.

Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7-14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.

The interlaminar connections in the primate primary visual cortex (V1) are well described, as is the presence of ongoing alpha-range (7-14 Hz) fluctuations in this area. Less well understood is how these interlaminar connections and ongoing fluctuations contribute to the regulation of visual spiking responses. Here, we investigate the relationship between alpha fluctuations and spiking responses to visual stimuli across cortical layers. Using laminar probes in macaque V1, we show that neural firing couples with the phase of alpha fluctuations, and that magnitude of this coupling is particularly pronounced during visual stimulation. The strongest modulation of spiking activity was observed in layers 2/3. Alpha-spike coupling and current source density analysis pointed to an infragranular origin of the alpha fluctuations. Taken together, these results indicate that ongoing infragranular alpha-range fluctuations in V1 play a role in regulating columnar visual activity.

The bottom-up processing of visual information is strongly influenced by top-down signals, at least part of which is thought to be conveyed from the frontal cortex through the frontal eye field (FEF) and the lateral intraparietal area (LIP). Here we investigated the architecture of multisynaptic pathways from the frontal cortex to the middle temporal area (MT) of the dorsal visual stream and visual area 4 (V4) of the ventral visual stream in macaques. In the first series of experiments, the retrograde trans-synaptic tracer, rabies virus, was injected into MT or V4. Three days after rabies injections, the second-order (disynaptically connected) neuron labeling appeared in the ventral part of area 46 (area 46v), along with the first-order (monosynaptically connected) neuron labeling in FEF and LIP. In the MT-injection case, second-order neurons were also observed in the supplementary eye field (SEF). In the next series of experiments, double injections of two fluorescent dyes, fast blue and diamidino yellow, were made into MT and V4 to examine whether the frontal inputs are mediated by distinct or common neuronal populations. Virtually no double-labeled neurons were observed in FEF or LIP, indicating that separate neuronal populations mediate the frontal inputs to MT and V4. The present results define that the multisynaptic frontal input to V4 arises primarily from area 46v, whereas the input to MT arises from not only area 46v but also SEF, through distinct FEF and LIP neurons. Segregated pathways from the frontal cortex possibly carry the functionally diverse top-down signals to each visual stream.

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT.

Decision-making via monitoring others’ actions is a cornerstone of interpersonal exchanges. Although the ventral premotor cortex (PMv) and the medial prefrontal cortex (MPFC) are cortical nodes in social brain networks, the two areas are rarely concurrently active in neuroimaging, inviting the hypothesis that they are functionally independent. Here we show in macaques that the ability of the MPFC to monitor others’ actions depends on input from the PMv. We found that delta-band coherence between the two areas emerged during action execution and action observation. Information flow especially in the delta band increased from the PMv to the MPFC as the biological nature of observed actions increased. Furthermore, selective blockade of the PMv-to-MPFC pathway using a double viral vector infection technique impaired the processing of observed, but not executed, actions. These findings demonstrate that coordinated activity in the PMv-to-MPFC pathway has a causal role in social action monitoring.

Axons in the mature mammalian central nervous system have only a limited capacity to grow/regenerate after injury, and spontaneous recovery of motor functions is therefore not greatly expected in spinal cord injury (SCI). To promote functional recovery after SCI, it is critical that corticospinal tract (CST) fibers reconnect properly with target spinal neurons through enhanced axonal growth/regeneration. Here, we applied antibody treatment against repulsive guidance molecule-a (RGMa) to a monkey model of SCI. We found that inhibition of upregulated RGMa around the lesioned site in the cervical cord resulted in recovery from impaired manual dexterity by accentuated penetration of CST fibers into laminae VII and IX, where spinal interneurons and motoneurons are located, respectively. Furthermore, pharmacological inactivation following intracortical microstimulation revealed that the contralesional, but not the ipsilesional, primary motor cortex was crucially involved in functional recovery at a late stage in our SCI model. The present data indicate that treatment with the neutralizing antibody against RGMa after SCI is a potential target for achieving restored manual dexterity in primates.

Parallel visual pathways in the primate brain known as the dorsal and ventral streams receive retinal inputs mainly through the magnocellular (M) and parvocellular (P) layers of the lateral geniculate nucleus. Inputs from these layers terminate within distinct parts of layer 4C of V1 (visual area 1). Due to the complexity of M- and P-derived neural connectivity in V1 and higher visual areas, the contributions of M and P inputs to the dorsal and ventral streams remain unclear. Employing retrograde transsynaptic transport of rabies virus, we analyzed the architecture of bottom-up pathways toward ventral stream area V4 (visual area 4) and dorsal stream area MT (middle temporal area). We found that V4 receives both M and P inputs "trisynaptically" from layer 4C via layer 2/3 of V1, whereas MT receives M-dominant input "disynaptically" from layer 4C via layer 4B of V1. V4 also receives disynaptic input from the dorsal stream portion of V2 (visual area 2) (i.e., cytochrome oxidase-stained thick stripes). Moreover, both M and P inputs reach V4 trisynaptically and MT disynaptically through "short-cut" pathways that bypass layer 4C of V1. The differential patterns of multisynaptic geniculo-cortical pathways to V4 and MT imply distinct modes of information processing in the dorsal and ventral streams.