Behavioral Neuroscience publications

Many substances and drugs are administered intranasally. These include opioid overdose reversal drugs, anti-epileptic medications, migraine medications, hormone treatments and medicines to treat/prevent allergies, colds and flus, including nasally administered vaccines, corticosteroids, antihistamines and decongestants. In addition, intranasal (IN) administration is the preferred route of entry by users of illicit drugs. Despite the widespread use of the IN route of administration, there is no established paradigm to access this route of administration preclinically to yield precise and reliable control over delivery. This poses major gaps in therapeutic discovery/testing, establishing pharmacokinetic/pharmacodynamic relationships of therapeutics and understanding the mechanisms of actions of therapeutics. Here we developed an in-dwelling microfluidic device that, when implanted upon the nasal bone in mice, accesses the nasal cavity to allow reliable and precise IN fluid delivery during freely moving behavior. We validated this device, called the nasal access port (NAP), to confirm it allows rapid and precise control of fluids. We further exemplified the application of the NAP for studying outcomes of IN cocaine in mice, including its pharmacokinetic profile, and both the rapid release of dopamine and behavioral effects upon IN cocaine. By achieving precise and reliable access to the IN route of administration, the NAP represents a substantial methodological advance with broad applicability in the biomedical and life sciences, especially in the neuroscience, pharmacology, medicinal chemistry and physiology domains.

Anxiety disorders are highly prevalent and often refractory to existing treatments, motivating the development of alternative neuromodulatory strategies. Peripheral bioelectronic approaches targeting the gut–brain axis such as vagus nerve stimulation (VNS) demonstrate that modulation of visceral afferent pathways can influence central emotional circuits. Gastric electrical stimulation (GES) is a clinically established therapy for gastrointestinal motility disorders. While the stomach is densely innervated by vagal afferents, the effect of GES on anxiety-related behavior has not been systematically examined. We sought to identify neural pathways engaged by GES and effects of continuous chronic GES on behavior. To do this, we developed a gastric stimulation platform for rodents, a fully implantable, untethered system enabling chronic neuromodulation in freely moving rats. We combined this with cross-species whole-brain activity mapping in mice to interrogate circuit-level mechanisms. Using open field and elevated plus mazes, together with machine-learning-based behavioral tracking and multivariate modeling, we show that acute GES induces a robust, context-dependent anxiogenic phenotype characterized by reduced exploration and increased freezing, particularly in novel open-field environments. In contrast, chronic GES produces a divergent post-stimulation behavioral profile marked by enhanced exploratory behavior relative to acutely stimulated animals, indicating temporally dynamic reorganization of anxiety-related behavior. Principal component analysis and hierarchical clustering further revealed that stimulation reshapes the multivariate structure of behavioral features rather than shifting animals along a single anxiety continuum. Whole-brain c-Fos mapping revealed anatomically distributed modulation of limbic–cortical networks following gastric stimulation, including suppression of ventral medial entorhinal cortex, excitation of nucleus tractus solitarii and heterogeneous recruitment of amygdalar and hippocampal subregions. These circuit-level patterns align with the behavioral dissociation between contextual exploration and explicit threat avoidance, providing convergent cross-species evidence that gastric stimulation engages distributed anxiety-related networks. Together, these findings establish the first freely moving behavioral model of chronic gastric neuromodulation, demonstrate temporally dynamic and context-sensitive effects on anxiety-like behavior, and provide systems-level validation that the stomach can serve as a viable peripheral access point for modulating central emotional circuits.

Through learning and memory, the cortex dynamically forms sensory associations to guide our behavior in an ever-changing environment. How memory-related brain regions, such as the medial-temporal lobe, influence sensory cortex to support this process remains unclear. Here, we used two-photon calcium imaging of axonal projections from the perirhinal (PRh) cortex to the auditory cortex during learning and generalization of an auditory discrimination task. PRh input in the auditory cortex increased during learning and influenced performance in a categorization task. Chemogenetically silencing PRh input selectively disrupted the activity of auditory cortex layer 2/3 pyramidal neurons, and PRh photoactivation drove behavior toward overgeneralization. These findings highlight PRh input as a key modulatory pathway that shapes cortical dynamics underlying auditory learning and memory-guided sensory perception.

The medial nucleus accumbens shell (medNAcSh) is a key regulator of hedonic feeding, controlling reward consumption through its projections to downstream structures. Recent studies showed that the primary cellular mediators of these effects are dopamine 1 receptor-positive striatal projection neurons (D1-SPNs). Specifically, D1-SPN activity gets inhibited during reward consumption, and such inhibition is necessary and sufficient to authorize consumption, independent of metabolic need. Anatomically, the medNAcSh spans 1–1.5 mm along the rostro-caudal axis in mice, and previous studies have reported functional gradients along this axis. For instance, pharmacological studies have suggested that rostral rather than caudal medNAcSh regulates appetitive behavior. However, the mechanisms underlying this topographical gradient remain unknown. Here, we hypothesized that D1-SPNs contribute to this gradient by regulating hedonic feeding via a specific hotspot in the rostral medNAcSh. Using calcium monitoring with fiber photometry in mice, we show that rostral medNAcSh D1-SPNs demonstrate inhibitory responses during reward consumption, while caudal D1-SPNs do not. Consistently, optogenetic stimulation of rostral D1-SPNs inhibits consumption, while stimulation of caudal D1-SPNs had minimal effects, confirming the existence of a functional rostro-caudal gradient. Importantly, we observed no differences between rostral and caudal D1-SPNs in their responses to aversive stimuli, suggesting that the D1-SPN gradient is specific to appetitive contexts. To investigate potential molecular correlates of this functional gradient, we leveraged open-source anatomy datasets and performed fluorescent in situ hybridization, identifying Stard5 and Peg10 as markers enriched in the rostral and caudal medNAcSh, respectively. Finally, we developed a novel Stard5-Flp driver line to selectively target the rostral hotspot and demonstrated that Stard5+ neurons recapitulate rostral D1-SPN activity patterns. Together, these findings establish a spatially confined rostral medNAcSh subregion as a critical regulator of reward consumption and introduce Stard5 as a molecular tool for its manipulation, offering new opportunities for intervention in dysregulated eating.

Pitch perception is fundamental to speech and music, yet the neural representation of pitch in auditory cortex remains poorly understood. We hypothesized that mice rely on temporal cues for pitch perception because of their wide auditory filters and high-frequency hearing. To investigate, we developed a mouse auditory filter bank model that estimates the temporal pitch salience of complex tones. We then trained mice to discriminate low vs. high fundamental frequencies (F0s) in complex tones and found that modeled temporal pitch salience was highly correlated with behavioral discrimination sensitivity. Widefield calcium imaging showed that the organization of periodotopy in auditory cortex predicts how well mice recognize temporal pitch cues. Mice trained on an F0 discrimination task had larger periodotopic maps with greater vector strengths than naïve mice, demonstrating experience-dependent expansion and refinement of temporal pitch maps in auditory cortex. Our findings establish mice as a robust model for studying the neural basis of temporal pitch perception.

Many perceptual skills improve with a few days of training. However, weeks or months of practice may be required to reach a level of expertise on complex tasks (Watson, 1980). Here, we explored how gerbils attain expertise on a difficult task: amplitude modulation (AM) rate discrimination at very shallow AM depths, similar to the depths used during vocal communication. Using an appetitive Go-Nogo procedure, we first trained 6 gerbils to perform an AM discrimination task (Nogo: 4 Hz; Go: 4.25-10 Hz) at a depth of 0 dB (re: 100% depth). Animals were then trained to perform AM discrimination at successively shallower depths, from -3 to -18 dB, requiring an average of 5-10 days of practice to reach a performance metric of d’≥1 for each depth. Finally, we determined that AM discrimination thresholds were nearly identical between 0 to -12 dB, and only slightly elevated at -15 dB. Improvements in performance were accompanied by a large reduction in response time during procedural learning, and a gradual reduction of response time during perceptual learning, even as AM depth became shallower (i.e., more difficult). The shallowest depth at which gerbils displayed peak performance on the AM discrimination task is similar to their lowest AM depth detection thresholds. These results suggest performance on challenging auditory perceptual tasks require prolonged practice, and is accompanied by increased automaticity (i.e., lower response time) that stabilizes once expertise is achieved.

Objective Traumatic brain injury (TBI) significantly reduces the quality of life for millions of survivors worldwide, causing persistent brain tissue damage and cognitive impairments, with no established therapeutic interventions currently available. Slow‐wave activity, a hallmark of deep sleep, has been implicated in recovery after TBI, but pharmacological approaches to enhance it lack specificity and scalability, complicating efforts to identify slow‐wave activity as a direct mechanistic contributor and severely limiting clinical translation. Methods To overcome these limitations, we developed a preclinical closed‐loop auditory stimulation (CLAS) paradigm that targets sleep's slow waves, enabling highly specific and temporally precise enhancement of slow‐wave activity. Therefore, we delivered 30‐ms sound triggers targeting the up‐phase of real‐time detected slow‐waves (upCLAS: TBI n = 8), or no sound stimulation (mockCLAS: non‐TBI n = 8, TBI n = 7) during sleep to healthy controls (non‐TBI) or brain injured (TBI) rats. Concomitantly, we assessed the ability of upCLAS‐enhanced sleep to counteract brain tissue damage (primary outcome) and symptomatic sequelae (secondary outcome) of TBI. Results Bayesian analysis revealed that sound‐mediated slow‐wave activity enhancement: (1) reduces diffuse axonal injury, with TBI mockCLAS posterior estimates falling outside the 95% confidence intervals of both other groups, whereas the posterior distributions of TBI upCLAS and non‐TBI groups largely overlapped (~13% posterior differences >0), consistent with a negligible effect size between groups; (2) decreases demyelination, with approximately 97% posterior differences >0 between TBI mockCLAS and TBI upCLAS groups, compared to approximately 60% between non‐TBI and TBI upCLAS groups; and (3) preserves cognitive ability, with recognition indexes in the novel object recognition test significantly above chance level in non‐TBI (* p = 0.031) and TBI upCLAS (* p = 0.026) groups, in contrast to mockCLAS‐treated TBI rats ( p = 0.156), presenting pronounced cognitive deficit. Furthermore, microglial response to brain injury was increased by deep sleep enhancement, with reduced ionized calcium‐binding adaptor molecule 1+ area coverage in TBI upCLAS rats (* p = 0.0445) compared to non‐TBI ones. Interpretation These results unambiguously demonstrate slow‐wave activity enhancement confers robust disease modification following TBI while overcoming major limitations of other preclinical approaches. Our findings constitute proof‐of‐concept that boosted sleep intensity mitigates histopathological and cognitive sequelae of brain trauma, suggesting that a clinically relevant, nonobtrusive, sleep‐based therapy may represent a novel therapeutic intervention for TBI survivors. ANN NEUROL 2026;100:242–254

Hearing is the largest modifiable mid-life risk factor for Alzheimer's disease (AD), yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.

Dysregulation of metabotropic glutamate receptor 5 (mGluR5) and cholecystokinin (CCK) signaling has been implicated in major depressive disorder (MDD), but the underlying circuit mechanisms remain unclear. Here, we define how mGluR5 regulates depressive‐like behaviors through CCK signaling in the entorhinal cortex (EC) to basolateral amygdala (BLA) pathway. Anatomical tracing and optogenetics show that CCK‐expressing neurons in the EC project to the BLA and that their activation increases glutamatergic activity in this region. Bidirectional circuit manipulation establishes causality: optogenetic stimulation induces, whereas inhibition alleviates, depressive‐like phenotypes. Expansion microscopy reveals postsynaptic mGluR5 enrichment along this pathway. Chronic social defeat stress (CSDS) downregulates mGluR5 in the BLA. Pharmacologically, mGluR5 antagonism phenocopies CCK‐driven pro‐depressive effects, whereas CCK knockout mice resist behavioral consequences of mGluR5 inhibition. Mechanistically, mGluR5 agonism suppresses CCK release, disrupts BLA long‐term potentiation, and mitigates CSDS‐induced behaviors. Circuit‐specific mGluR5 knockdown in the EC CCK →BLA pathway increases stress susceptibility. These findings identify an mGluR5‐CCK axis within an EC CCK →BLA circuit that governs stress‐induced affective states.

Dopamine is essential for striatal function and learning. Striatal dopamine release can be triggered by dopamine cell firing, but also by coordinated cholinergic interneuron activity, which stimulates dopamine release via presynaptic nicotinic acetylcholine receptors on dopamine axons. While acetylcholine-dependent dopamine release is well-documented ex vivo and under artificial optogenetic stimulation in vivo , its role during natural behavior has remained unclear. One possible endogenous driver of acetylcholine-dependent dopamine release is thalamic input, which provides strong excitatory drive to cholinergic interneurons. To examine whether thalamic input provokes acetylcholine-dependent dopamine release during behavior, we performed simultaneous fiber photometry recordings of striatal dopamine (GRAB-rDA3m) and thalamic axon activity (gCaMP8m) in the dorsomedial (DMS) and dorsolateral striatum (DLS) of mice learning the accelerating rotarod, a striatal-dependent task that demands precise and effortful motor control. Recordings were obtained on- and off-task and across days of training to capture the full arc of learning. Dopamine transients in DMS, but not DLS, were frequently coupled to peaks in thalamic axon activity via an acetylcholine-dependent mechanism. The occurrence of these thalamic-evoked DMS dopamine transients depended on learning, task engagement, and the recent history of dopamine activity, but did not contribute to motor error signals. Together, these findings establish thalamic input as a physiological driver of acetylcholine-dependent dopamine release in DMS. Moreover, they reveal that striatal sensitivity to this local release mechanism is dynamically gated by dopaminergic history, providing a compelling framework for understanding how local and soma-triggered dopamine signals are coordinated to support learning.

Quickly adapting behavior to changing environments is key for survival. Brain dopamine signals reinforce actions that procure rewards and avoid adverse outcomes. However, the molecular mechanisms within the circuits that actuate these signals at subsecond timescales remain unexplored. We show that midbrain endocannabinoid mobilization is the conditio sine qua non for behavioral invigoration evoked by external cues. Reward- and punishment-predictive signals require intact retrograde release of the endocannabinoid 2-arachidonoylglycerol (2-AG) from ventral tegmental area dopamine neurons. Moreover, we show that genetic deletion of presynaptic cannabinoid type-1 receptors (CB1Rs), the target for 2-AG, recapitulates behavioral and dopaminergic deficits. Exploiting causal inference tools to interpret continuous brain signals, we describe that 2-AG/CB1R communication is essential for striatal dopamine release to signal salient cues and propel conditioned responding. These findings reveal an endocannabinoid-mediated disinhibition mechanism exploited by dopamine neurons to orchestrate striatal dopamine release events, enabling adaptive action selection informed by cues.

Our ability to generalize abstract rules to new situations is a cognitive hallmark, yet its neural basis is unclear. We identified a thalamocortical circuit essential for this process in mice. During a cross-modal rule transfer task, medial prefrontal cortex (mPFC) neurons encoded task rules across sensory modalities to enable generalization. Crucially, mediodorsal thalamus (MD) projections to mPFC were causally required: Inhibiting this pathway destabilized mPFC representations and impaired rule transfer, whereas enhancing it improved performance. Without MD input, mPFC recruited distinct populations for each task, losing cross-context stability. Direct mPFC excitation impaired generalization, underscoring the specificity of thalamic regulation. Thus, the MD stabilizes mPFC activity for flexible rule transfer—a mechanism with implications for cognitive disorders and artificial intelligence.

Parkinson’s disease (PD) is marked by impairments in voluntary movement, including prolonged movement preparation and execution, yet how parkinsonism alters neural processing to produce these deficits remains unresolved. Prior work examining M1 spiking activity in parkinsonian states has largely characterized firing-rate changes and motor representations at the level of individual neurons, with inconsistent results and limited insight into population-level organization. Here we investigated how parkinsonism reshapes the population-level organization of neural activity in M1 during movement. We simultaneously recorded large populations of neurons from M1 in two nonhuman primates performing reaching tasks before and after induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the parkinsonian state, both preparation and reach durations were significantly prolonged. Population-level analyses revealed that parkinsonism increased the dimensionality of M1 activity during both preparation and movement and reduced the orthogonality between preparatory and movement-related subspaces. Moreover, trial-by-trial variability in reach duration was explained by the alignment of the preparatory and reach subspaces, indicating the functional role of subspace orthogonality. Together, these findings suggest that parkinsonism disrupts the population-level organization of cortical dynamics across computations, providing a population-level framework linking altered cortical dynamics to the movement-related dysfunction observed in PD.

Cochlear implants (CIs) have successfully restored hearing in more than one million patients with severe to profound hearing loss worldwide. Although CIs effectively restore speech perception in quiet environments, sound localization remains challenging for bilateral CI users, particularly their ability to utilize interaural time differences (ITDs). The majority of clinical CI processors use a coding strategy that encodes ITD information only in the envelope of electrical pulse trains rather than their pulse timing, which may contribute to the poorer spatial hearing perception of CI users. We recently demonstrated in a behavioural study on early deafened, bilaterally CI‐implanted rats that pulse timing ITDs completely dominate ITD perception, whereas sensitivity to envelope ITDs is almost negligible in comparison. Building on this, we here investigated the neurophysiological sensitivity of the inferior colliculus (IC) to envelope and pulse timing ITDs at two different pulse rates (900 and 4500 pulses/s) and three different stimulation modulations (5, 20 and 100 Hz) in CI rats with different hearing experiences. Our results indicate that IC neurons exhibit far greater sensitivity to pulse timing ITD than envelope ITD independent of pulse rate, modulation rate or hearing experience. These findings suggest that to improve binaural hearing outcomes in bilateral CI users, clinical stimulation strategies should provide informative pulse timing ITDs. image Key points Current bilateral cochlear implants mostly provide time cues of arriving sound in the envelope of stimulation rather than in the timing of pulses. A behavioural study on cochlear implanted rats has shown that pulse timing dominates binaural hearing. Here we examined the neural sensitivity to independent changes in time cues presented on the envelope or pulse timing, respectively, in rats with bilateral cochlear implants and different hearing experiences. Auditory midbrain neurons were consistently more sensitive to changes in pulse timing rather than envelope, irrespective of stimulus pulse rate, modulation rate or an animal's hearing experience.

Internal states including stress and satiety, affect cue-induced feeding behaviors, yet the underlying neural mechanisms remain poorly understood. The nucleus of the solitary tract (NTS), a key hindbrain hub that integrates interoceptive and viscerosensory signals and projects to reward processing nuclei, is anatomically well-positioned to modulate cue-induced feeding behaviors in response to internal state changes. Using behavioral paradigms combined with chemogenetics and fibre photometry, this study investigated the hypothesis that NTS mediates the effects of stress and satiety on cue-induced feeding behaviors via A2 neurons and modulation of ventral tegmental area (VTA) dopamine signaling. We first showed that both foot shock stress and outcome specific satiety (i.e., sucrose prefeed) reduced cue-induced appetitive behavior. Inhibition of NTS neurons only attenuated the suppressive effect of foot shock stress, but not that of outcome specific satiety, indicating that NTS is required for stress-induced suppression of cue-induced appetitive behavior. Further investigation into the contributing neural phenotype revealed that stimulation of NTS A2 neurons reduced conditioned approach and suppressed cue-evoked VTA dopamine neural activity, without any effects on lateral hypothalamus (LH) neuron activity. Together, these findings suggest that NTS neurons mediate the effects of foot shock stress, but not outcome specific satiety, on cue-induced appetitive behavior, in part through activation of NTS A2 neurons and modulation of cue-evoked VTA dopamine neural activity. These results provide an NTS-mediated mechanism through which stress suppresses cue-induced feeding behavior.

Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum primarily via the ventral and intralaminar thalamus, respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.

Many neurological and psychiatric disorders stem from maladaptive conditioning and resist treatment. Tinnitus, as one example, is the distressing perception of sound in the absence of an external source. One of the network systems implicated in multiple disorders is the 'salience network', associated with positive/negative reward, habit formation, motivation, valuation and mood. However, it is not known whether directly modulating the 'salience network' at its anatomical and physiological core, in the ventral striatum, more specifically the nucleus accumbens, could be beneficial. Here we show that a novel treatment approach, targeting the salience network, can reduce tinnitus perception in a rat model. We found that bilateral rewarding stimulation of the nucleus accumbens, when paired with non-tinnitus tones, was most effective. A combined approach using rewarding accumbens stimulation and dysrewarding lateral habenula stimulation - paired with non-tinnitus and tinnitus tones, respectively - also suppressed tinnitus but caused negative effects. Our results demonstrate how the rewarding stimulation can recondition brain networks to effectively remove the salience of tinnitus frequencies. We anticipate that our unique reconditioning strategy has broader therapeutic applications for other brain disorders rooted in maladaptive learning.

Traumatic brain injuries (TBIs) are more than mere lesions and generate a persistent secondary pathology. This, combined with functional reorganization of circuits post-injury, may explain the increased risk for psychiatric disorders in patients with TBI. In the current studies, we demonstrate that frontal TBI changed the Pavlovian behavioral response to reinforcer-predicting cues and reduced the motivational value of cues. TBI also chronically impaired decision-making on a gambling-like task with reinforcer-paired cues. To investigate how these changes occur, we evaluated the nucleus accumbens (NAc) core. At a subacute time point (14 days), we confirmed reduced input to the NAc with optogenetics and evaluated electrophysiological and transcriptional changes. TBI increased neuronal excitability and the single nucleus RNA sequencing profile indicated a substantial stress and inflammatory response, but also high indicators of plasticity, particularly in D1- and D2-positive medium spiny neurons. To evaluate how these subacute changes transitioned to chronic NAc dysfunction, we measured immunohistochemical surrogates of activity post-mortem and recorded calcium activity from the NAc after TBI during Pavlovian conditioning. TBI reduced histological markers of activity and reduced cue-evoked calcium activity. Overall, these data indicate that substantial reorganization of the NAc occurs following frontal brain injury. A primary effect of this is to reduce the salience of environmental cues linked to outcomes. The inability to properly process outcomes could contribute to broader psychiatric symptoms after TBI, including impairments in decision-making, behavioral flexibility, and impulsivity but also presents a potential treatment target.

Flexible behavior requires decision-making that integrates both perceptual and mnemonic-related information. While the dorsal premotor cortex (PMd) is known to support perceptual decision-making, its contributions to decisions based on mnemonic information for motor planning remain underexplored. Here, we investigate local field potential (LFP) oscillations in the PMd of monkeys performing a transitive inference task requiring the formation and retrieval of mnemonic representations of an arbitrarily defined rank order among perceptual items. The difficulty of this operation depends on the distance of the items in the mnemonic representation. We tested the hypothesis that this symbolic distance (SD) systematically modulates PMd oscillatory activity in a frequency-specific manner during decisions that combine perceptual identification with mnemonic retrieval. Consistent with this hypothesis, PMd exhibited local and reliable SD-dependent changes across low (Theta, Alpha, Beta) and high-Gamma (h-Gamma) frequency bands, and related to behavioral performance. These findings provide evidence that the PMd integrates perceptual and mnemonic information through coordinated modulations of oscillatory activity, extending its role beyond perceptual mapping to support abstract, memory-guided decisions.

Interpersonal coordination is fundamental to social evolution. We investigate its phenomenology and neural underpinnings in humans and macaques, examining the behavioral adaptations required for mutual coordination during motor interactions and the extent to which the underlying brain mechanisms are shared across species. Using a common interpersonal coordination paradigm, we conducted functional magnetic resonance imaging (fMRI) in humans and intracranial local field potential (LFP) recordings in macaques. Despite between-species behavioral discrepancies, both monkeys and humans coordinate through adjustments that proved to be based on proactive adaptation of motor planning and execution. Evidence from fMRI and time-resolved decoding analysis of LFPs converged to show modulation of premotor brain activity associated with interpersonal coordination and its effectiveness. Moreover, a dynamic sequential coding emerged, whereby the action context is represented early during planning, and coordination features near movement onset. Our findings reveal an evolutionarily conserved cortical architecture across primates that supports cooperative motor behavior.