LFP publications

With practice, rapid early gains in performance are followed by a slower phase marked by kinematic refinement, automaticity and enhanced cortical and striatal interactions. While sleep is known to support early learning, its causal role in the slow phase of learning is not known. Here we recorded neuronal activity in primary motor cortex (M1) and the dorsolateral striatum (DLS) during long-term skill acquisition and interleaved sleep. Surprisingly, the slow phase of learning was marked by the emergence of a previously unrecognized 5–10 Hz oscillatory activity during NREM sleep that was coherent across M1 and DLS. This oscillation resulted in repeated joint reactivation of task-specific information in cortex and striatum. Strikingly, during later stages of training, such joint reactivation of task activity increased over the course of NREM sleep, suggesting that sleep-dependent processing strengthens cortico-striatal interactions. The strength of M1–DLS coherence was predictive of next-day performance gains and increased cortico-striatal coupling during task performance. Targeted closed-loop disruption of this oscillation during NREM sleep abolished performance gains, whereas switching to a dose-matched random stimulation paradigm enabled performance improvements in the same animals. Importantly, the same cortico-striatal 5–10 Hz rhythm was also found in sleeping non-human primates, where it was selectively enhanced following learning. Together, we identify, across species, a novel NREM sleep oscillation that is important for sleep-dependent performance gains which depend on cortico-striatal processing.

Neuromodulation is widely employed to enhance neural activity and restore impaired circuitry, yet current methods suffer from invasiveness, limited depth, or poor spatial resolution. Temporal interference stimulation (TIS) has emerged as a non-invasive approach to modulate deep brain regions via interference of high-frequency electric fields, achieving spatial selectivity. Despite its potential, the physiological effects remain unexplored. Here, we present a customized liquid metal-based neural interface to record electrophysiological responses to TIS across diverse neural tissues, from brain organoids to mouse brains. The softness of the interface minimizes invasiveness while ensuring stable access to deep neural regions. Electrophysiological analyses reveal TIS-induced dynamics in neurodevelopment and functional connectivity. Furthermore, we investigated latent neural dynamics, presenting population-level neural activity, to compare responses across models of differing complexity and maturity. By combining soft neural interfaces with multi-scale analyses, this study uncovers how neuromodulation shapes neural dynamics and supports the development of future therapeutic strategies.

Current disease-sensing devices primarily focus on distinguishing between healthy and diseased states, effective for diagnosis but limited in guiding optimal intervention timing for prevention. We developed a tripartite framework identifying pre-disease state in depression, a reversible phase preceding irreversible onset. Using complex systems theory, we analyzed early-warning signals emerging as biological systems approach critical transitions. Continuous monitoring of nine multimodal biomarkers—spanning electrophysiological, behavioral, and biological—enabled classification into normal, pre-disease, and disease states by quantitatively defining critical points. An artificial intelligence agent classified disease states with 95.2% accuracy using multimodal data, enabled by ultrasoft neural probes for stable, low-damage recordings. Therapeutic validation with a skin-attachable wireless vagus nerve stimulator integrating soft three-dimensional electrodes demonstrated superior efficacy during pre-disease states. Subjects treated during pre-disease showed faster recovery and greater therapeutic responses, while those treated after disease onset failed to achieve full recovery. This framework provides evidence-based rationale for early intervention.

In mammals, slow-wave sleep is characterized by synchronized neuronal activity that alternates between on and off periods. Slow-wave activity (SWA) and synchrony reflect sleep need, are correlated with synaptic strength in cortical circuits and promote synaptic downselection and memory consolidation. Here we assessed whether these core benefits of sleep can be obtained during waking. We locally induced alternating on/off periods during wakefulness using optogenetics in mice. This led to a local ipsilateral reduction in SWA and synchrony during subsequent sleep, and to reduced markers of synaptic strength. Moreover, bilateral induction of off periods over sensorimotor cortex during sleep deprivation restored memory consolidation. Thus, inducing on/off activity during wakefulness is sufficient to reduce local sleep need and fulfill core functions of sleep.

Magnetogenetic deep brain stimulation (MG‐DBS) represents a wireless neuromodulation that has demonstrated long‐lasting behavioral benefits in Parkinson's disease models. However, the circuit‐level mechanisms underlying these therapeutic effects have remained uncharacterized due to limitations of conventional neural interfaces. We present a bio‐integrable soft neural interface featuring ultrasoft liquid‐metal probes with bioresorbable stiffeners and customizable interconnects directly printed onto cranial surfaces to match individual skull anatomy and nanoparticle injection sites. This platform enables stable multi‐regional recordings from deep brain structures without chronic tissue damage. We systematically investigate MG‐DBS therapeutic mechanisms in a Parkinson's disease mouse model. Circuit‐level analysis reveals that MG‐DBS modulates pathological beta‐band oscillations and inter‐regional synchrony across the cortico‐basal ganglia‐thalamic circuit. Direct comparison with conventional electrical DBS demonstrates that MG‐DBS effects persisted approximately fifteen‐fold longer after stimulation cessation. Our electrophysiological recordings elucidate the mechanistic basis for this sustained therapeutic effect, providing unprecedented insights into magnetogenetic neuromodulation dynamics.

Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of vigilance. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). We report an acute induction of a dissociated state, characterised by prominent slow oscillations in the cortex and marked pupil dilation in behaviourally awake, moving animals. REM sleep was initially markedly suppressed, but was overcompensated in the subsequent 48 hours, while administration of 5-MeO-DMT immediately after sleep deprivation attenuated the subsequent rebound of sleep slow-wave activity. We argue that the occurrence of a dissociated state combining features of waking and sleep may fundamentally underpin the known and hypothesised effects of psychedelics — from dream-like hallucinations to reopening of the critical period for plasticity.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. We found that PVNs act like a volume knob in the mouse auditory cortex (ACtx), bi-directionally adjusting neural and perceptual sensitivity to sound level over a 20 dB range. PVN-based gain adjustments were "sticky," such that a single bout of PVN activation at 40 Hz-but not at 1 or 70 Hz-sustainably dampened ACtx sound responsiveness, enhanced feedforward inhibition, and behaviorally desensitized mice to loudness. We then developed a mouse model of adult-onset hyperacusis by demonstrating ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity following a restricted noise-induced cochlear lesion. We found that several minutes of 40-Hz PVN stimulation in noise-exposed mice sustainably dampened ACtx hyperactivity and restored normal loudness sensitivity for 1 week. These findings demonstrate that sensory disorders caused by permanent peripheral injuries can be reversed by patterned stimulation of cortical circuits that directly regulate perception.

Basal forebrain cholinergic neurons (BFCNs) densely innervate auditory cortex (ACtx), conveying signals linked to internal brain states and external sensory cues. Acetylcholine (ACh) is known to rapidly modulate cortical circuits through nicotinic ACh receptor (nAChR)-mediated activation of layer 1 inhibitory neurons (L1-INs). However, BFCN terminals are also abundant in deeper layers, where their functional impact has received less attention. Using multi-plex in situ labeling across cortical layers and cell types, we found that layer 6 pyramidal neurons (L6-PNs) are highly enriched in diverse transcripts for nAChR subunits and muscarinic ACh receptors (mAChRs). In vivo optogenetic activation of BFCN axons revealed persistent modulation of regular spiking units in L2-6 but a rapid phasic activation only in L6. In acute slices, optogenetic activation of BFCN axons elicited fast nAChR-mediated excitatory post-synaptic potentials in L6-PNs, comparable to responses in L1-INs, and slower mAChR-mediated inhibitory responses. These findings identify L1-INs and excitatory L6-PNs as two major hubs for BFCN modulation of cortical circuits. By recruiting distinct receptor mechanisms and circuit motifs in L1 and L6, BFCNs may engage parallel pathways of cholinergic control that couple fast, transient modulation with slower, sustained regulation to shape cortical perception and plasticity.

Speech production entails several processing steps that encode linguistic and articulatory structure, but whether these computations correspond to spatiotemporally discrete patterns of neural activity is unclear. To address this issue, we use electrocorticography to directly measure the brains of neurosurgical participants performing an interactive speech paradigm. We observe a broad range of cortical modulation profiles, and subsequent clustering analyses establish that responses comprised distinct classes associated with sensory perception, planning, motor execution, and task-related suppression. These activity classes are also localized to separate neural substrates, indicating their status as specialized networks. We then parse dynamics in the planning and motor networks using unsupervised dimensionality reduction, which reveals subnetworks that are sequentially active throughout preparation and articulation. These results therefore support and extend a localizationist model of speech production where cortical activity "flows" within and across discrete pathways during language use.

Physical exercise acutely improves hippocampus-dependent memory. Whereas animal studies have offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis of exercise-induced effects on hippocampal-cortical circuits remains unknown. Experimental evidence supports the idea that hippocampal sharp wave-ripples (SWR) play a critical role in learning and memory. Coupling between SWRs in the hippocampus and neocortex may reflect modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal-cortical ripple dynamics in the human brain. We performed intracranial recordings in epilepsy patients undergoing pre-surgical evaluation, during awake resting state, before and after an exercise session. Exercise increased ripple rate in the hippocampus. Exercise also enhanced the coupling and phase-synchrony between cortical ripples in the limbic and the default mode (DM) cortical networks and hippocampal SWRs. Further, a higher heart rate during exercise, reflecting exercise intensity, was related to a subsequent increase in resting state ripples across specific cortical networks, including the DM network. These results offer the first direct evidence that a single exercise session elicits changes in ripple events, a well-established neurophysiological marker of mnemonic processing. The characterisation and anatomical distribution of the described modulation points to hippocampal ripples as a potential mechanism by which exercise elicits its reported short-term effects in cognition.

The non-rapid-eye movement (NREM) sleep power spectrum is composed of rhythmic and arrhythmic components, respectively associated with brain rhythms and scale-free dynamics. Both components are hypothesized to represent distinct processes underlying sleep-dependent memory consolidation as well as other brain complex processes. Recent advancements in spectral parametrization techniques and the use of multifractal models have enabled new insights into these components and their connection to brain networks. Aging impacts NREM sleep oscillations, but no animal studies considered the impact of age on rhythmic and arrhythmic components. In this study, we assessed the effects of age on the power spectrum and its two components using local field potential recordings in mice. We recorded across the cerebral cortex and within the hippocampus—a central brain hub involved in NREM sleep-dependent cognitive processing. Ten younger (7.6 months) and eleven older (15.7 months) C57BL/6 J male and female mice were continuously recorded over a 24-hour period. We extracted the NREM sleep standard and rhythmic spectra, controlled for scale-free activity, and estimated multifractal arrhythmic properties during NREM sleep using the Wavelet Leader and Bootstrap based MultiFractal analysis toolbox. Older mice showed specific alterations in both components compared to younger animals: reduced rhythmic gamma power in the anterior cortex, greater regional differentiation of scaling exponents, and higher multifractal dispersion of the arrhythmic component in the hippocampus. These findings demonstrate that aging alters rhythmic and arrhythmic properties of NREM sleep in distinct brain regions, suggesting that both contribute to age-related changes in sleep-dependent cognition.

Primate societies rely on the production and interpretation of social signals, in particular those displayed by the face. Facial movements are controlled, according to the dominant neuropsychological schema, by two separate circuits, one originating in medial frontal cortex controlling emotional expressions, and a second one originating in lateral motor and premotor areas controlling voluntary facial movements. Despite this functional dichotomy, cortical anatomy suggests that medial and lateral areas are directly connected and may thus operate as a single network. Here, we test these contrasting hypotheses through structural and functional MRI (fMRI) guided electrical stimulation and simultaneous multichannel recordings from key facial motor areas in the macaque monkey brain. These areas include medial facial motor area M3 (located in the anterior cingulate cortex); two lateral face-related motor areas: M1 (primary motor) and PMv (ventrolateral premotor); and S1 (primary somatosensory cortex). Cortical responses evoked by intracortical stimulation revealed that medial and lateral areas can exert significant functional impact on each other. Simultaneous recordings of local field potentials in all facial motor areas further confirm that during facial expressions, medial and lateral facial motor areas significantly interact, primarily in the alpha and beta frequency ranges, whereas during voluntary chewing, coupling occurs at lower frequencies. These functional interactions varied across facial movement types. Thus, at the cortical level, the control of facial movements is not mediated through independent (medial/lateral) functional streams, but results from an interacting sensorimotor network.

Memory consolidation enables animals to draw on past experiences to guide future behavior. This process involves system- and synaptic-level changes and predominantly occurs during sleep. While hippocampal-cortical circuits are well studied in this context, the contributions of other systems, including dopaminergic circuits—key players in learning-related processes—remain poorly understood. Ventral tegmental area dopaminergic (VTA DA ) neurons are active during sleep and suggested to participate in memory consolidation processes; however, causal evidence for this is lacking. Using calcium-dependent fiber photometry, electrophysiology, and chemogenetic and optogenetic manipulations across learning paradigms, we explore the functions of VTA DA neuronal activity during sleep. We show that VTA DA activity during nonrapid eye movement sleep is experience dependent, is enhanced by motor skill and associative learning, facilitates motor skill memory consolidation, and exhibits a motor learning–dependent increase in temporal coordination with cortical spindle oscillations. Our findings uncover a previously unidentified function for VTA DA neurons in consolidating memories during sleep, advancing understanding of this central neuromodulator’s functions in regulating fundamental biological processes.

Objective. Infrared neural stimulation (INS) has emerged as a potent neuromodulation technology, offering safe and focal stimulation with superior spatial recruitment profiles compared to conventional electrical methods. However, the neural dynamics induced by INS stimulation remain poorly understood. Elucidating these dynamics will help develop new INS stimulation paradigms and advance its clinical application. Approach. In this study, we assessed the local network dynamics of INS entrainment in the auditory thalamocortical circuit using the chronically implanted rat model. Our approach focused on measuring INS energy-based local field potential (LFP) recruitment induced by focal thalamocortical stimulation. We further characterized linear and nonlinear oscillatory LFP activity in response to single-pulse and periodic INS and performed spectral decomposition to uncover specific LFP band entrainment to INS. Finally, we examined spike-field transformations across the thalamocortical synapse using spike-LFP coherence coupling measures. Main results. We found that INS significantly increases LFP amplitude as a log-linear function of INS energy per pulse, primarily entraining to LFP β and γ bands with synchrony extending to 200 Hz in some cases. A subset of neurons demonstrated nonlinear, chaotic oscillations linked to information transfer across cortical circuits. Finally, we utilized spike-field coherences to correlate spike coupling to LFP frequency band activity and suggest an energy-dependent model of network activation resulting from INS stimulation. Significance. We show that INS reliably drives robust network activity and can potently modulate cortical field potentials across a wide range of frequencies in a stimulus parameter-dependent manner. Based on these results, we propose design principles for developing full coverage, all-optical thalamocortical auditory neuroprostheses.

Context‐dependent sensory processing within the predictive coding framework relies on detecting mismatches between incoming stimuli and internal predictive models. Sensory deviants elicit prediction errors, seen as enhanced neural responses, that update these models and influence attention and behaviour. Although prediction errors have been widely observed across brain regions, the downstream processes remain poorly understood. In this study, we recorded electrocorticography in five urethane‐anaesthetised rats and identified cortical slow oscillations, characterised by spontaneous transitions between ‘Up’ and ‘Down’ states. Deviant stimuli in an auditory oddball paradigm evoked an initial positive prediction error, followed by a prolonged, all‐or‐nothing response which spread in a travelling wave across the cortex. Identified as putative evoked cortical Up states, these responses were not evoked by standards, omissions or a many‐standards control. Up states following deviants occurred more recently after a previous Up state when compared to spontaneous Up states. In preliminary data from an awake rat, long‐latency Up states were not present spontaneously or evoked. In a different rat, anaesthetic depth was key to spontaneous and evoked Up states, with more robust Up/Down states and more reliable triggering of Up states under deeper anaesthesia. These results suggest that sensory deviants may cause shifts in cortical state under anaesthesia, explaining the long‐latency mismatch response under anaesthesia and sleep.

As part of a deep brain stimulation (DBS) procedure, direct electrophysiological recordings from thalamic and basal ganglia circuits were obtained from a pediatric participant with secondary dystonia to examine the neural mechanisms of motor timing. The participant performed a two-phase repetitive timing task that began with synchronization to a series of externally presented auditory cues, followed by a continuation phase in which the participant maintained the movement rhythm without external guidance. Simultaneous recordings from stereoelectroencephalography (sEEG) leads implanted in the globus pallidus internus (GPi), subthalamic nucleus (STN), ventral oralis (Vo), centromedian nucleus (CM), and thalamic nuclei receiving projections from the cerebellum (ventral intermediate nucleus (VIM) and centrolateral nucleus (CL)) revealed behaviorally relevant neural dynamics. Local field potentials (LFPs) from recorded nuclei exhibited strong, time-locked responses during the synchronization phase, with reduced amplitudes during the continuation phase. Time-frequency analysis showed consistent power increases around the corresponding mean of the inter-response intervals (IRIs) in both behavioral output and neural signals, suggesting frequency-specific entrainment across circuits. These findings suggest of cerebellar-thalamic and basal ganglia contributions to temporal coordination.

Cerebral cortex and cerebellum are essential for sensorimotor control, but the dynamics of their interactions remain unclear. Here, we investigated which pathways prevail during preparation and execution of spontaneous whisker movements in mice. During preparation, neuronal activity of primary motor (M1) and somatosensory (S1) cortex precede that of cerebellar crus regions, with a lead that is consistent with relaying a copy of motor commands. After movement onset, the phase of the signal inverts, indicating a dominant vector signaling from cerebellum to cerebrum. At this stage, Purkinje cell activity correlates more with S1 than M1, generating a prediction of sensory consequences during motor actions. A computational cerebello-cortical model could replicate the changes in dynamics and directionality. Optogenetic manipulations of pons and thalamus confirm the modeled predictions on stage-dependent dynamics. Together our data point towards a swap in direction of information flow between cerebrum and cerebellum when motor preparation switches to execution.

Introduction Deep brain stimulation (DBS) is a neuromodulation method for treatment of various neurological disorders. Research on DBS has often focused on local inhibition or excitation effects, at the site of stimulation. However, it is well-known that DBS can lead to robust evoked potentials (EP) not only at the stimulation site, representing the local effect, but also in distant brain regions, representing the effects on distant targets. While the significance of these EPs for therapeutic outcomes is not known, it appears that the electrical effects of DBS have a partial modulatory impact on downstream targets. Nonetheless, it partly remains unclear through what mechanism DBS pulses travel to the distant targets or what portion of the pulses travel along the normal pathways from the stimulation site. The possible scenarios include orthodromic or antidromic pathways, accessory pathways, normally inhibited pathways, and direct electromagnetic activation of distant sites. We hypothesize that the pathways that transmit DBS pulses include the pathways that transmit intrinsic neural signals. Methods To test this, we performed a transfer function analysis on deep brain recordings from children with dystonia, during DBS-off condition and compared its impulse response with the transmission of signals from electrical stimulation during DBS-on condition. We compared impulse responses derived from intrinsic neural signals during voluntary movement (DBS-off) to evoked potentials (EPs) recorded during electrical stimulation (DBS-on), focusing on directional transmission (orthodromic vs. antidromic). Results DBS EPs were more accurately predicted by impulse responses corresponding to direct axonal activation rather than somatic relay. Significant correlations between intrinsic signal transfer functions and EPs, particularly in orthodromic directions ( p -value < 0.01) from pallidum to thalamus and subthalamic nucleus, support our hypothesis that DBS travels along physiological pathways. Discussion These results suggest that DBS engages existing motor pathways to reach distant targets, offering mechanistic insight into its network effects. This supports future approaches that could tailor treatment plans based on individual connectivity maps to improve clinical efficacy of DBS.

Identifying neural signatures of loss of consciousness is a major goal of neuroscience. The local/global auditory novelty paradigm has been useful in characterizing sensory processing across arousal states. Propofol suppresses responses to long‐term novelty (global deviance, GD) at subhypnotic doses; suppression of responses to short‐term novelty (local deviance, LD) outside auditory cortex may represent a biomarker of loss of consciousness. Dexmedetomidine is an alpha‐2 adrenergic agonist that induces sleep‐like sedation. This study examined whether the changes in auditory novelty processing observed with propofol, a GABA‐ergic agent, also occur with dexmedetomidine and during sleep. Intracranial recordings were obtained in neurosurgical patients undergoing monitoring for refractory epilepsy. Stimuli were vowel sequences incorporating LD and GD. Neural activity was recorded during wakefulness, administration of dexmedetomidine, and sleep and was examined as the averaged evoked potential (AEP) and high gamma (70–150 Hz) power. AEP responses were more broadly distributed than high gamma activity. Results previously observed with propofol were replicated with dexmedetomidine. Subhypnotic doses led to decreased LD effects and a precipitous decline in GD effects. Loss of responsiveness was associated with loss of LD effects outside the auditory cortex. Likewise, daytime sleep was associated with cessation of GD effects and confinement of LD effects to the auditory cortex. Results support the generalizability of changes in auditory novelty processing to dexmedetomidine and sleep. Preservation of LD effects in the auditory cortex indicates that the auditory cortex continues to monitor the environment following loss of responsiveness.

The mediodorsal thalamic nucleus (MD) forms neural circuits with various brain regions, including the prefrontal cortex (PFC), the reticular thalamic nucleus (TRN), and the midbrain reticular nucleus (MRN). However, the specific roles and underlying mechanisms in auditory information processing remain unclear. Here, we perform multi-channel electrophysiological recordings in awake mice to investigate the response patterns of the MD to auditory stimuli, as well as the regulatory effects of PFC, MRN, and TRN inputs. We identify two distinct types of sound-evoked responses. The Phasic-response features a transient burst firing to the stimulus with short latency, rapidly adapting to baseline and corresponding to the onset fluctuation of the local field potential. The Sustained-response is marked by prolonged firing with longer latency and is accompanied by persistent enhancement of oscillatory power following stimulus offset. The response patterns of MD neurons remain consistent across different types of auditory stimuli. Optogenetic inactivation of the MRN suppresses both response types in the MD. The Sustained-response is attenuated by PFC inactivation but enhanced by TRN inactivation, while the Phasic-response remains unaffected by inactivation of either the PFC or TRN. Our findings expand the understanding of the MD's role in sound information integration and auditory cognitive regulation.