Transcranial focused ultrasound (tFUS) enables non-invasive access to deep brain structures with high spatial precision, but its mechanisms of action remain elusive and under active investigation. The leading hypothesis posits that tFUS exerts its neuromodulatory effects through direct activation of neurons, while others attribute effects to indirect activation of auditory pathways. Here, we investigated the neuromodulatory effects of tFUS on the dentato– thalamo–cortical (DTC) pathway by targeting either the lateral cerebellar nucleus (LCN) or auditory cortex (AUD) in anesthetized rats. Electroencephalography (EEG) recordings from bilateral motor cortices and the contralateral auditory cortex revealed that tFUS reliably evoked cortical potentials, whereas sham stimulation produced no responses. Both LCN and AUD stimulation activated the auditory cortex, suggesting auditory pathway involvements. However, only LCN stimulation elicited early and significant event-related potentials and gamma-band activity in the contralateral motor cortex, consistent with DTC pathway engagement. We propose that LCN-targeted stimulation engages the DTC pathway through modulation of neuronal excitability, while concurrent auditory inputs account for global cortical activation. These results are consistent with a hybrid mechanism in which tFUS modulates neuronal dynamics, converging both direct and indirect components depending on the stimulation site. Proposed framework reconciles competing views of tFUS as either a direct or indirect modulator and clarifies how ultrasound can differentially influence cortical circuits depending on the stimulation target.
Diagnosis in epilepsy depends on several distinct objectives—including interictal epileptiform discharge (IED) detection, source localisation of epileptiform activity, and seizure classification—each shaped by the underlying sensing technology. This review examines the opportunities that quantum magnetic sensing offers within this diagnostic framework, with particular emphasis on translational readiness and clinical potential. Seizure classification is included to situate the broader clinical context of epilepsy diagnostics, whereas the review of quantum sensing evidence is focused on IED detection and presurgical source localisation, the objectives for which such evidence currently exists. Magnetoencephalography (MEG) provides non-invasive source localisation that complements electroencephalography (EEG), and its clinical adoption is increasingly determined by advances in magnetic sensor technology. Optically pumped magnetometer (OPM)-based MEG represents the most clinically developed quantum sensing application, progressing from proof-of-concept in 2020 toward small-cohort clinical feasibility studies from 2022 onwards. By enabling on-scalp recordings at reduced sensor-to-brain distance, OPM-MEG improves signal amplitude and permits flexible sensor placement, with early evidence of benefit in paediatric populations and mesial temporal lobe epilepsy. However, current evidence derives from small, heterogeneous cohorts, and no prospective data yet link OPM-MEG to surgical outcomes. 4He-OPMs represent an early feasibility stage with IED detection comparable to superconducting quantum interference device (SQUID)-MEG in small case series; nitrogen-vacancy centres in diamond and silicon carbide divacancy magnetometry remain preclinical, constrained by a fundamental standoff-sensitivity trade-off. We conclude that OPM-MEG is best positioned as a complementary modality within established presurgical workflows, with prospective multicentre outcome studies representing the critical next step toward clinical translation.
Head direction (HD) cells in the anterodorsal thalamic nucleus form the brain’s internal compass, and are often modeled as a ring attractor maintaining azimuth coding by leveraging continuous visual and inertial sensory input. Here, we test how the common experimental preparation of head-fixed animals alters this code. Complete head-fixation that creates vestibular conflict disrupts both unit and population encoding of head direction, while selectively constraining head-on-body movements either in real or virtual reality uniquely impairs HD population activity. More specifically, attractor dynamics are altered in head-restrained male mice during periods of immobility, and a computational model recapitulates this effect by perturbing lateral connectivity among HD neurons. These dynamics recover several hundred milliseconds prior to locomotion onset, suggesting that an efference copy or prediction of a re-afferent signal is necessary to maintain HD network activity during head restraint. More generally, the results indicate that the HD network is a context- and state-dependent predictive estimator, stabilized by forthcoming self-motion signals. The classic ring-attractor models should be revised to integrate context-dependent dynamics with prospective motor signals, offering a more complete account of how the brain’s compass remains stable across both naturalistic and constrained conditions.