The Role of Striatum in Controlling Waiting during Reactive and Self-Timed Behaviors The ability to wait before responding is crucial for many cognitive functions, including reaction time (RT) tasks, where one must resist premature actions before the stimulus and respond quickly once it is presented. However, the brain regions governing waiting remain unclear. Using localized excitotoxic lesions, we investigated the roles of the motor cortex (MO) and sensorimotor dorsolateral striatum (DLS) in male rats performing a conditioned lever-release task with variable delays. Neural activity in both MO and DLS showed similar firing patterns during waiting and responding periods. However, only bilateral DLS lesions caused a sustained increase in premature (anticipatory) responses, whereas bilateral MO lesions primarily prolonged RTs. In a self-timing version of the task, where rats held a lever for a fixed delay before releasing it, DLS lesions caused a leftward shift in response timing, leading to persistently greater premature responses. These waiting deficits were accompanied by reduced motor vigor, such as slower reward-orienting locomotion. Our findings underscore the critical role of the sensorimotor striatum in regulating waiting behavior in timing-related tasks.
The laminar pattern of proprioceptive activation in human primary motor cortex The primary motor cortex (M1) is increasingly being recognized for its vital role in proprioceptive somatosensation. However, our current understanding of proprioceptive processing at the laminar scale is limited. Empirical findings in primates and rodents suggest a pronounced role of superficial cortical layers, but the involvement of deep layers has yet to be examined in humans. Submillimeter resolution functional magnetic resonance imaging (fMRI) has emerged in recent years, paving the way for studying layer-dependent activity in humans (laminar fMRI). In the present study, laminar fMRI was employed to investigate the influence of proprioceptive somatosensation on M1 deep layer activation using passive finger movements. Significant M1 deep layer activation was observed in response to proprioceptive stimulation across 10 healthy subjects using a vascular space occupancy (VASO)-sequence at 7 T. For further validation, two additional datasets were included which were obtained using a balanced steady-state free precession sequence with ultrahigh (0.3 mm) in-plane resolution, yielding converging results. These results were interpreted in the light of previous laminar fMRI studies and the active inference account of motor control. We propose that a considerable proportion of M1 deep layer activation is due to proprioceptive influence and that deep layers of M1 constitute a key component in proprioceptive circuits.
A general framework for characterizing optimal communication in brain networks Efficient communication in brain networks is foundational for cognitive function and behavior. However, how communication efficiency is defined depends on the assumed model of signaling dynamics, e.g., shortest path signaling, random walker navigation, broadcasting, and diffusive processes. Thus, a general and model-agnostic framework for characterizing optimal neural communication is needed. We address this challenge by assigning communication efficiency through a virtual multi-site lesioning regime combined with game theory, applied to large-scale models of human brain dynamics. Our framework quantifies the exact influence each node exerts over every other, generating optimal influence maps given the underlying model of neural dynamics. These descriptions reveal how communication patterns unfold if regions are set to maximize their influence over one another. Comparing these maps with a variety of brain communication models showed that optimal communication closely resembles a broadcasting regime in which regions leverage multiple parallel channels for information dissemination. Moreover, we found that the brain’s most influential regions are its rich-club, exploiting their topological vantage point by broadcasting across numerous pathways that enhance their reach even if the underlying connections are weak. Altogether, our work provides a rigorous and versatile framework for characterizing optimal brain communication, and uncovers the most influential brain regions, and the topological features underlying their influence.
Hippocampal perineuronal net degradation identifies prefrontal and striatal circuits involved in schizophrenia-like changes in marmosets In schizophrenia, anterior hippocampus (aHipp) overactivity is associated with orbitofrontal cortex (OFC) dysfunction, but the contribution to symptomatology is unknown. In rodents, degradation of the hippocampal perineuronal net (PNN) replicates this overactivity, but uncertainty over rodent/human prefrontal homology limits translation to humans. Here, we test the hypothesis that aHipp PNN degradation in a species with a human-like prefrontal cortex, the marmoset, alters aHipp-striatal and aHipp-OFC circuitry. Microdialysis and [18F]-fluoro-l-dihydroxyphenylalanine positron emission tomography identified increased dopamine synthesis in the associative striatum, but not the nucleus accumbens, as is seen in schizophrenia, and elevated dopamine and noradrenaline in the OFC. Behaviorally, activity was elevated in a marmoset version of the amphetamine-induced activity test, and impaired probabilistic discrimination learning was seen in an OFC/striatum-dependent task that computational modeling suggests was due to loss of goal-directed behavior. Together, these findings demonstrate that a loss of primate aHipp PNNs is sufficient to induce striatal and prefrontal dysfunction consistent with that observed in humans with schizophrenia.
Human sensorimotor cortex reactivates recent visuomotor experience during awake rest The re-emergence of task-related activation patterns during awake rest has been reported to play a role in memory consolidation and perceptual learning. This study aimed to test whether such reactivation occurs in the primary sensorimotor cortex following a visuomotor task. During functional magnetic resonance imaging (fMRI) scanning, 42 healthy participants (13 women and 29 men) learned visuomotor tracking, while a rotational perturbation was introduced between the cursor position and joystick angle. This visuomotor task block was interleaved with a control block, during which participants passively viewed a replay of their previously performed cursor movements. Half of the participants used their right hand, whereas the other half used their left hand to control the joystick. Resting-state scans were acquired before and after the visuomotor task sessions. A multivariate pattern classifier was trained to classify task and control blocks and was then tested on resting-state scans collected before and after the task session. Results revealed a significant increase in the number of volumes classified as “task” during post-task rest compared with pre-task rest, indicating re-emergence of task-related activity. Representational similarity analysis also showed a greater similarity to task-related patterns during the post-task rest period. Furthermore, this effect was specific to the left primary sensorimotor cortex contralateral to the hand used and significantly correlated with motor improvement following rest. Our findings reveal the reactivation of recent task-related experience in the primary sensorimotor cortex.
Mapping global brain reconfigurations following local targeted manipulations Understanding how localized brain interventions influence whole-brain dynamics is essential for deciphering neural function and designing therapeutic strategies. Using longitudinal functional MRI datasets collected from mice, we investigated the effects of focal interventions, such as thalamic lesions and chemogenetic silencing of cortical hubs. We found that these local manipulations disrupted the brain’s ability to sustain network-wide activity, leading to global functional connectivity (FC) reconfigurations. Personalized mouse brain simulations based on experimental data revealed that alterations in local excitability modulate firing rates and frequency content across distributed brain regions, driving these FC changes. Notably, the topography of the affected brain regions depended on the intervention site, serving as distinctive signatures of localized perturbations. These findings suggest that focal interventions produce consistent yet region-specific patterns of global FC reorganization, providing an explanation for the seemingly paradoxical observations of hypo- and hyperconnectivity reported in the literature. This framework offers mechanistic insights into the systemic effects of localized neural modulation and holds potential for refining clinical diagnostics in focal brain disorders and advancing personalized neuromodulation strategies.
Hippocampal output suppresses orbitofrontal cortex schema cell formation Both the orbitofrontal cortex (OFC) and the hippocampus (HC) are implicated in the formation of cognitive maps and their generalization into schemas. However, how these areas interact in supporting this function remains unclear, with some proposals supporting a serial model in which the OFC draws on task representations created by the HC to extract key behavioral features and others suggesting a parallel model in which both regions construct representations that highlight different types of information. In the present study, we tested between these two models by asking how schema correlates in rat OFC would be affected by inactivating the output of the HC, after learning and during transfer across problems. We found that the prevalence and content of schema correlates were unaffected by inactivating one major HC output area, the ventral subiculum, after learning, whereas inactivation during transfer accelerated their formation. These results favor the proposal that the OFC and HC operate in parallel to extract different features defining cognitive maps and schemas.
Anatomically resolved oscillatory bursts reveal dynamic motifs of thalamocortical activity during naturalistic stimulus viewing Natural vision requires circuit mechanisms which process complex spatiotemporal stimulus features in parallel. In the mammalian forebrain, one signature of circuit activation is fast oscillatory dynamics, reflected in the local field potential (LFP). Using data from the Allen Neuropixels Visual Coding project, we show that local visual features in naturalistic stimuli induce in mouse primary visual cortex (V1) retinotopically specific oscillations in various frequency bands and V1 layers. Specifically, layer 4 (L4) narrowband gamma was linked to luminance, low-gamma to optic flow, and L4/L5 epsilon oscillations to contrast. These feature-specific oscillations were associated with distinct translaminar spike-phase coupling patterns, which were conserved across a range of stimuli containing the relevant visual features, suggesting that they might constitute feature-specific circuit motifs. Our findings highlight visually induced fast oscillations as markers of dynamic circuit motifs, which may support differential and multiplexed coding of complex visual input and thalamocortical information propagation.
The Neural Oscillatory Basis of Perspective-Taking in Autistic and Non-Autistic Adolescents Using Magnetoencephalography Taking another’s perspective is a high-level mental skill underlying many aspects of social cognition. Perspective-taking is usually an embodied egocentric process whereby people mentally rotate themselves away from their physical location into the other’s orientation. This is accompanied by increased theta-band (3–7 Hz) brain oscillations within a widespread fronto-parietal cortical network including the temporoparietal junction. Individuals with autism spectrum conditions (ASC) have been reported to experience challenges with high-level perspective-taking, particularly when adopting embodied strategies. To investigate the potential neurophysiological basis of these autism-related individual differences, we used magnetoencephalography in combination with a well-replicated perspective-taking paradigm in a group of 18 autistic and 17 age-matched non-autistic adolescents. Findings revealed that increasing the angle between self and other perspective resulted in prolonged reaction times for the autistic group during perspective-taking. This was accompanied by reduced theta power across a wide network of regions typically active during social cognitive tasks. On the other hand, the autistic group showed greater alpha power decreases in visual cortex compared with the non-autistic group across all perspective-taking conditions. These divergent theta and alpha power effects, coupled with steeper response time slopes, suggest that autistic individuals may rely more on alternative cognitive strategies, such as mental object rotation, rather than an egocentric embodied approach. Finally, no group differences were found when participants were asked to track, rather than take, another’s viewpoint, suggesting that autism-related individual differences are specific to high-level perspective-taking.