In a groundbreaking study illuminating the neural mechanisms of motor timing, researchers have uncovered a dynamic cortico-basal ganglia network that integrates flexible timing signals critical for movement initiation. The anterior lateral motor cortex (ALM), a key corticobasal area, has long been implicated in motor planning, but its interaction with subcortical regions like the striatum has remained elusive. This latest work sheds light on how timing information is generated, maintained, and restored via network interactions, fundamentally advancing our understanding of neural integration underlying precise motor behavior.
Utilizing sophisticated electrophysiological techniques and optogenetic silencing methods in mice, the study probed the striatum’s role during periods of ALM inactivation. Remarkably, the striatum was found to retain crucial timing information even when its cortical input was largely suppressed. Although a majority of striatal neurons displayed decreased firing rates during ALM silencing, indicative of the ALM’s prominent excitatory drive, residual neuronal activity persisted. This residual activity preserved the rank order of neuronal firing and could predict the timing of specific motor outputs, such as licking behaviors, at the single-trial level.
The residual activity in the striatum during ALM silencing suggests that striatal circuits embody an intrinsic capacity to encode temporal information. Nevertheless, the characteristic ramping activity—gradual increase of neuronal firing rates associated with timing—was abolished during ALM inactivation. This finding implies that although the striatum sustains timing information, the ALM provides essential excitatory input necessary to drive ramp dynamics. The disruption of these ramping patterns underscores the indispensable role of cortical signals in modulating subcortical integrator states.
Based on these findings, the researchers proposed a sophisticated integrator model involving cortico-basal ganglia loops in which the striatum and potentially other intermediate subcortical structures—such as the substantia nigra reticulata and thalamus—function cooperatively as a ‘subcortical integrator.’ Within this framework, the ALM acts both as an input source and a receiver of timing signals, orchestrating the dynamics of the entire network. This bidirectional relationship ensures flexibility and stability in motor timing representations.
The model further differentiates the ALM inputs into two distinct components. First, there exists an ‘on-manifold’ input aligned precisely along the direction of temporal integration within the striatal state space. This input is temporally integrated by the subcortical network to generate scalable timing signals that match behavioral demands. This component likely corresponds to neuronal modes associated with prior trial history, effectively encoding past temporal context to influence ongoing timing computations.
Conversely, the second component consists of ‘off-manifold’ inputs that provide widespread excitatory drive, enhancing the overall activity level in the striatum without directly contributing to time representation. This amplification sustains the robustness of neural firing but is orthogonal to the integrative axis. Importantly, ALM silencing eradicates both components simultaneously, which halts temporal integration and attenuates striatal firing rates.
Intriguingly, when ALM silencing ceases, the network rapidly restores excitatory drive, allowing striatal activity to rebound to baseline. Simultaneously, the resumption of on-manifold inputs reactivates timing dynamics along normal trajectories. This dynamic recovery manifests as a parallel shift in neural activity patterns, demonstrating the system’s remarkable resilience and flexibility in maintaining motor timing precision despite transient disruptions.
These insights were bolstered by computational modeling that examined the nature of temporal integration within feedforward and recurrent network architectures. The study found that feedforward networks could reproduce both sequential and ramping activities observed experimentally. Moreover, modeling the ALM as both an input and follower within a subcortical integrator distinctly recapitulated the experimentally observed pauses in time representation following perturbations.
Notably, alternative network motifs failed to reproduce these key dynamics, emphasizing that the precise configuration of cortico-subcortical interactions is critical for flexible motor timing. This computational evidence corroborated the experimental findings, positioning the striatum and associated subcortical nuclei as integral components of a distributed timing integrator that relies heavily on cortical drive from the ALM.
The complexity of temporal integration mechanisms is underscored by the dual role of ALM inputs in shaping striatal activity—simultaneously encoding temporal progress and modulating excitability. This dual-input model suggests a sophisticated neural code where timing and excitatory state are dissociable yet intertwined within basal ganglia circuits. Such a framework allows for nuanced control of motor timing, allowing organisms to adapt flexibly to environmental and contextual demands.
Further experimental manipulations targeting striatal activity promise to elucidate the causative role of these subcortical circuits in timing behavior. The current findings strongly motivate future studies to probe how specific neuronal populations within the striatum contribute to integrative timing functions and how these may interact with cortical signals during learning and adaptative motor control.
This work provides compelling evidence that the cortico-basal ganglia loop is not merely a conduit for motor commands but a dynamic neural integrator implementing flexible timing computations essential for coordinated behavior. The delineation of on-manifold and off-manifold ALM inputs opens new avenues to dissect the neural code underlying motor timing and to understand disorders characterized by timing deficits.
In summary, these findings illuminate fundamental principles of temporal integration within brain circuits critical for motor timing. By demonstrating the dual role of ALM inputs and the striatum’s subcortical integrative function, the research lays a foundation for novel paradigms in studying motor control and its dysfunction. This knowledge has profound implications for neurodegenerative conditions and neuropsychiatric disorders where basal ganglia circuits are disrupted, paving the way for targeted therapeutic interventions.
Subject of Research: Neural mechanisms underlying flexible motor timing in cortico-basal ganglia circuits.
Article Title: Integrator dynamics in the cortico-basal ganglia loop for flexible motor timing.
Article References:
Yang, Z., Inagaki, M., Gerfen, C.R. et al. Integrator dynamics in the cortico-basal ganglia loop for flexible motor timing. Nature (2025). https://doi.org/10.1038/s41586-025-09778-2
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41586-025-09778-2
Keywords: Cortico-basal ganglia loop, motor timing, temporal integration, striatum, anterior lateral motor cortex (ALM), neural dynamics, feedforward networks, computational modeling, excitatory drive, timing representation, neural integrator, motor control.
