LFP publications

The cortex generates diverse neural dynamics, ranging from broadband fluctuations to narrowband oscillations at specific frequencies. Here, we investigated whether broadband and oscillatory dynamics play different roles in the encoding and transmission of visual information. We used information-theoretical measures to dissociate neural signals sharing common information (i.e., redundancy) from signals encoding complementary information (i.e., synergy). We analyzed electrocorticography (ECoG) and local field potentials (LFP) in the visual cortex of human and non-human primates (macaque) to investigate the extent to which broadband signals (BB) and narrowband gamma (NBG) oscillations conveyed synergistic or redundant information about images. In both species, the information conveyed by BB signals was highly synergistic within and between visual areas. By contrast, the information carried by NBG was primarily redundant within and between the same visual areas. Finally, the information conveyed by BB signals emerged early after stimulus onset, while NBG sustained information at later time points. These results suggest a potential dual role of BB and NBG cortical dynamics in visual processing, with broadband dynamics supporting nonlinear pattern recognition and oscillations facilitating information maintenance across the cortex.

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.

Background Transcranial electrical stimulation (TES) has limited spatial focus and depth penetration, constraining its therapeutic efficacy. Intersectional Short-Pulse (ISP) stimulation was developed to overcome these limitations by delivering rapidly switching pulses that can be temporally integrated by neuronal membranes. Here, we aimed to establish the biophysical basis of ISP-induced temporal summation and to test whether this mechanism enables effective brain modulation in vivo. Methods We combined finite-element modeling, cadaver measurements ( n = 2 human cadavers), and biophysically realistic NEURON simulations to characterize the spatial and temporal properties of ISP-induced electric fields. In vivo whole-cell patch-clamp recordings were performed in the rat somatosensory cortex (female Wistar rat) to test the membrane-level integration of sequential electric field pulses. Functional efficacy was evaluated using closed-loop ISP stimulation in a hippocampal kindling model of temporal lobe epilepsy in male Long–Evans rats ( n = 11 animals, >500 induced seizures analyzed across conditions). Results Here we show that neurons integrate sequential ISP pulses in a non-vectorial, temporally accumulative manner, consistent with membrane-level charge integration rather than extracellular field superposition. ISP and conventional TES simulations produced similar instantaneous field magnitudes, but ISP stimulation resulted in more uniform neuronal excitability across brain depths. Closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 45% and 35% compared to SHAM stimulation and conventional TES, and significantly reduced motor seizure severity. Conclusions ISP stimulation provides a non-invasive neuromodulation approach that enhances deep brain engagement through rapid, temporally structured pulse sequences. These findings demonstrate effective seizure suppression in a rodent model and support the translational potential of ISP for disorders involving pathological neural dynamics.

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.

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.

Non-rapid eye movement (NREM) sleep is not uniform but characterized by brief intrusions of wake-like brain activity and increased muscle tonus known as micro-arousals or brief awakenings. Although micro-arousals are an inherent feature of human and animal sleep, knowledge about the neural correlates of micro-arousals is sparse. We here developed an algorithm for automatic detection of micro-arousals based on EMG activity and used it to analyse the associated laminar neural activity in the motor cortex in mice. Our analysis showed that short micro-arousals with a duration below 5 s were associated with decreased cortical firing, while longer micro-arousals with a duration of 5–10 s were associated with increased firing in a similar manner to transitions to wakefulness. Analysis of single-channel firing showed that some channels exhibited increased activity immediately prior to micro-arousals, while others exhibited decreased activity. Slow wave activity (SWA, 1–4 Hz) immediately after micro-arousals was tightly correlated with sleep pressure and even surpassed average SWA levels during NREM sleep in sleep deprived animals. This study provides new insights into the neural mechanisms associated with micro-arousals and identifies a new link between sleep architecture and sleep homeostasis.

The development of motor control in primary motor cortex (M1) requires both movements and neural activity. In rats, cortical motor control first appears around postnatal day (P) 25, prior to which movements are generated by subcortical motor nuclei such as the red nucleus (RN). While these subcortically generated movements are thought to provide the activity that guides the development of M1, the specific movements associated with M1 activity and their somatotopic and temporal precision remain unknown. Here, we performed acute electrophysiological recordings of neural activity in the forelimb region of M1 of P12–24 rats as they cycled between sleep and wake and compared M1 and RN activity in P24 rats. At every age, M1 neurons exhibited somatopically precise activity during REM sleep twitches, along with strong activity during wake movements. From P12 to P24, the proportion of neurons exhibiting twitch-related activity decreased, twitch-related activity became more temporally refined, and a larger fraction of spikes occurred before movement onset. At P24, M1 showed less premovement activity than RN. Further, in contrast to the non-selective activity seen in M1, some RN neurons showed movement-selective activity patterns during wake, firing only during particular wake movements. These findings reveal that movement-related activity in M1 is somatotopically precise by P12 and temporally precise by P24. But M1 still lacks the strong premovement activity and selectivity characteristic of RN, suggesting that at P24, subcortical outputs remain the main drivers of M1’s movement-related activity.

Male bushcrickets produce complex species-specific songs to attract mating partners. Since the neuronal processing underlying song-pattern detection is not fully understood, we analysed extracellularly recorded song-induced spike responses and local field potentials across the first stage of auditory processing in the prothoracic ganglion of Mecopoda elongata. We analysed the influence of the temporal structure and of any change in amplitude of spiking and local field potentials. We presented the complete chirp and compared the neuronal response pattern with those responses evoked individually by each pulse of the chirp. Our data revealed: (i) the complete chirp leads to a transient summation in local field potentials over the time course of the chirp, and (ii) significantly fewer action potentials occur during the chirp presentation than to the individually presented pulses. Our data provide insights into the question of how an acoustical signal can be used to extract those features from sensory information that are important for auditory behaviour, such as chorus formation, species recognition, or phonotaxis.

The unique gyral patterns of the human brain demand patient‐specific neural interfaces to achieve precise neuromodulation, mitigate adverse tissue responses, and optimize therapeutic efficacy and safety. One‐size‐fits‐all, conventional rigid electrocorticography (ECoG) electrodes, standardized for mass production through lithographic techniques, exhibit limited conformability to the brain's heterogeneous cortical topography. This mechanical mismatch results in poor electrode‐tissue contact, signal loss, and foreign body responses. To address these limitations, we present an integrated novel platform, synergizing MRI‐based anatomical mapping, finite element analysis (FEA)—optimized mechanical design, and direct ink writing (DIW) 3D printing to fabricate electrodes customized to individual gyral patterns. The resulting honeycomb‐inspired printable gel electrode (HiPGE) employs a bioinspired honeycomb architecture with ultra‐soft hydrogels, engineered to match the bending stiffness of brain tissue (0.1–10 kPa) while maintaining cost‐efficiency and long‐term durability. This mechanical congruence ensures exceptional cortical conformability and adaptive interfacing, circumventing the geometric and material limitations of traditional rigid electrodes. By combining patient‐specific design with scalable fabrication, our platform establishes a transformative framework for neural interface engineering, enhancing precision, biocompatibility, and functional performance in neuromodulation therapies and neuroprosthetic applications.

Reconstructing speech from neural recordings is crucial for understanding human speech coding and developing brain-computer interfaces (BCIs). However, existing methods trade off acoustic richness (pitch, prosody) for linguistic intelligibility (words, phonemes). To overcome this limitation, we propose a dual-path framework to concurrently decode acoustic and linguistic representations. The acoustic pathway uses a long-short term memory (LSTM) decoder and a high-fidelity generative adversarial network (HiFi-GAN) to reconstruct spectrotemporal features. The linguistic pathway employs a transformer adaptor and text-to-speech (TTS) generator for word tokens. These two pathways merge via voice cloning to combine both acoustic and linguistic validity. Using only 20 min of electrocorticography (ECoG) data per human subject, our approach achieves highly intelligible synthesized speech (mean opinion score = 4.0/5.0, word error rate = 18.9%). Our dual-path framework reconstructs natural and intelligible speech from ECoG, resolving the acoustic-linguistic trade-off.

Background: In Parkinson's disease, motor network electrophysiology frequently exhibits excessive beta oscillations. The cornerstone of therapeutic efficacy lies in the ability to modulate these pathological oscillations. Transcranial alternating current stimulation (tACS), a non-invasive method that applies oscillating electric fields to modulate ongoing brain activity, offers a promising approach. Objective: The objective of the manuscript is to investigate the dose-dependent effects of tACS on motor network cortical neurons in a Parkinson's disease model. Methods: We recorded neuronal spike activity in the motor cortex in parkinsonian non-human primates during tACS to determine how stimulation-induced electric fields affect spike timing. Results: Strong electric fields entrained neural activity at the stimulation frequency but altered the preferred spiking phase. Conversely, weak fields disrupted beta-band synchronization by modulating spike timing and phase preference. Frequency-matched stimulation significantly enhanced entrainment when aligned with endogenous oscillatory activity. Conclusion: Thus, with appropriately chosen stimulation parameters, tACS exhibits significant potential for controlling and modulating pathological oscillatory patterns that are characteristic of many neurological disorders.

Harmonicity is a property of complex sounds such as vocalizations or music, but it remains unclear how harmonicity is processed in the auditory cortex (ACtx). Subregions of ACtx are thought to process harmonic stimuli differently. Selective responses to sound features in ACtx emerge hierarchically from primary ACtx (A1) L4 and secondary ACtx (A2) layer (L)2/3, which is believed to be the most responsive to harmonic sounds. Since harmonic stacks can range from 2 to >10 components, being more similar to naturalistic vocalizations, harmonic sensitivity might also arise hierarchically across layers and areas. We studied responses to harmonic stacks of 2–10 frequencies across A1 L4, A1 L2/3, and A2 L2/3 in adult male and female mice using in vivo two-photon microscopy. We found harmonic-sensitive neurons (HNs) responding only to harmonic stacks but not to individual frequencies in all areas at similar proportions. HNs showed highly nonlinear spectral integration of harmonic frequencies that decreased as the harmonic stacks became more complex. Specifically, onset-biased HNs showed greater nonlinearity than offset-biased HNs only in A1 L4. Moreover, HNs in A1 L4 exhibited higher signal correlation than A2 L2/3. Sound-responsive neurons in A1 L4 have the weakest noise correlation compared with A1 L2/3 and A2 L2/3. Together, harmonic sensitivity is not a unique feature of A2 L2/3 but is already established in A1 L4, where neurons robustly encode harmonic sounds through sparse connections.

Habituation is a crucial sensory filtering mechanism whose dysregulation can lead to a continuously intense world in disorders with hypersensitivity. Although habituation is often termed the simplest form of learning, its circuit mechanisms remain elusive. Conventional peripheral explanations fail to fully account for long-term habituation in complex sensory environments, leading to theories proposing top-down regulation. Here we evaluated two competing top-down mechanistic explanations for habituation in mice (growth in predictive filtering and waning of novelty-driven amplification) and identified an unexpected role for the orbitofrontal cortex (OFC) in predictive filtering. After daily sound exposure, neural habituation in the primary auditory cortex (A1) was reversed by inactivating the OFC. Top-down projections from the OFC, but not other frontal areas, carried predictive signals that grew with daily sound experience and suppressed A1 via somatostatin-expressing inhibitory neurons. Thus, prediction signals from the OFC cancel out anticipated stimuli by generating their 'negative images' in sensory cortices.

Theta oscillations - rhythmic patterns of synchronous activity within discrete brain regions - are known to support memory, navigation, and behavioral coordination, and are sensitive to pharmacological manipulation. Acute ethanol (EtOH) exposure has been shown to alter theta oscillations, but its effects on transient theta bursts and cross-regional coordination during naturalistic behavior remain unclear. We recorded local field potentials (LFPs) from the medial septum (MS), hippocampal Cornu Ammonis 1 (CA1), and medial prefrontal cortex (mPFC) in freely foraging mice following intraperitoneal injection of EtOH (1.5 g/kg) or saline. We analyzed spectral power, theta burst dynamics, phase, and lag timing. Burst features from CA1 were used to train a machine learning classifier to predict session condition. EtOH impaired locomotion and reduced goal-directed behaviors, particularly early in the session. In CA1, theta power shifted toward lower frequencies and lagged coherence declined. EtOH increased the frequency but reduced the duration of theta bursts in CA1, and in MS, only burst count increased. EtOH enhanced the temporal alignment of MS-CA1 burst pairs. Phase-locking between CA1 and MS during coupled bursts remained present but showed altered structure. Our classifier achieved robust performance using burst features such as skew and entropy, and reliably distinguished treatment conditions. EtOH modulates septohippocampal dynamics by altering the timing and structure of theta bursts. These results suggest that burst-level features are sensitive markers of EtOH's circuit-level effects during naturalistic behavior.

The entorhinal-hippocampal system constitutes a pivotal neural circuit in the central nervous system. It is critically involved in processing spatial learning and memory. However, the specific neural interactions between entorhinal inputs and intra-hippocampal subcircuits that underlie spatial coding remain elusive. To address this gap, we integrated multimodal approaches including in vivo calcium imaging, dual-color optogenetic manipulation, chemogenetic intervention, electrophysiological recordings, immunohistochemistry, and Morris water maze (MWM) behavior to dissect how entorhinal-hippocampal afferents modulate hippocampal computations. Intriguingly, CA1-projecting CA3 neurons exhibited pronounced hyperactivity during early spatial learning, with activity gradually declining after sustained task performance. Chemogenetic inactivation of medial entorhinal-hippocampal afferents attenuated both neural responses of CA1-projecting CA3 neurons and the performance of spatial learning, hinting that medial entorhinal cortex (MEC) inputs to the hippocampus are essential for animals to execute spatial tasks precisely. By implementing dual-light theta-burst stimulation to co-activate ChrimsonR-expressing CA3-CA1 afferents and Chronos-expressing MEC-CA1 terminals, we observed robust heterosynaptic long-term potentiation in the dorsal CA1 region in vitro brain slice. This neuroplasticity was mediated synergistically by activating both NMDA receptors and voltage-gated calcium channels. Our findings establish that entorhinohippocampal afferents exert multilevel regulatory control over hippocampal function, thereby advancing mechanistic understanding of memory-related neurological pathologies.

The flexibility of human vocal production is well studied, but the direct role of the auditory system in regulating vocalizations in rodents remains largely unexplored. We show that during vocalizations, a fraction of rat auditory cortex neurons shows pre-call activity and different patterns of responses during calls and playback of calls. Additionally, we classified five auditory cortical vocalization responses: pre-call activated, onset activated, onset suppressed, ramping activated and ramping suppressed neurons. Intriguingly, onset suppressed cells can predict vocalization duration and occurrence. Injecting the auditory cortex with muscimol (GABA_A receptor agonist) prolonged vocalizations, while injecting the auditory cortex with gabazine (GABA_A receptor antagonist) shortened them. Similar reductions in call duration were observed during external white-noise stimulation of the auditory cortex and/or other auditory brain structures, resembling the effects of gabazine. Together, neuronal recordings, pharmacological interference and noise induced vocal modifications indicate direct modulation of vocal productions by the rat auditory cortex.

Reduction in neuronal firing from wake to sleep, i.e., sleep firing rate homeostasis (sFRH), is essential for restorative sleep. Sleep dysfunction is common in Parkinson's disease (PD), but sFRH has not been investigated. Here, using a within-subject design in the nonhuman primate model of PD, we report that thalamocortical sFRH is disrupted in parkinsonism. These findings can inform therapeutic approaches tailored to normalize sFRH and reestablish restorative sleep in PD.

Background With age, even mild acoustic injuries can accumulate - ultimately leading to a characteristic clinical picture of age-related hearing loss with the risk of cognitive decline. Age-related hearing loss is currently attributed to the loss of a most vulnerable auditory fiber type contributing to hearing in background noise. Here, we investigated the potential of a new drug, a more stable chemical variant of Dendrogenin B (DX243) that is predicted to display a protective function on neurite outgrowth, rather than on cell survival. Methodology In the rat animal model, DX243 was tested on hearing thresholds, cortical local field potentials (LFP), auditory steady-state responses (ASSR), auditory brainstem responses (ABR), growth function of notched-noise stimuli, inner hair cell (IHC) ribbon numbers, and multi-click pulse responses (MCP) before and after auditory trauma (AT). Results No auditory evoked LFP response changes were seen in the prefrontal cortex, visual cortex, or hippocampus. In contrast, a permanent decline of auditory evoked LFP amplitudes in the auditory cortex (AC) was measured 2 weeks after AT. Daily injection of DX243 for 2 weeks prevented the AT-induced decline in LFP activity, a protective effect that continued for 6 weeks following the final injection. Through a protective effect of DX243 on a trauma-induced decline of LFP in response to amplitude-modulated tones >80 Hz, a subcortical origin of the drug-effect was suggested. DX243 showed no effect on hearing sensitivity and did not affect subcortical processing of sound features that depend on phase-locking at the stimulus onset (e.g., near-threshold ASSR responses, close-to-threshold ABR growth functions, or spontaneous cortical LFP responses). However, with the same dose-response dependency as shown for cortical LFP effects, DX243 significantly protected from AT-induced decreases in ABR growth functions for loud sound stimuli and in background noise, protected from AT-induced loss of IHC ribbons and AT-induced decline of fast ABRs with decreasing time intervals. Conclusion These findings suggest DX243 as a novel neuroprotective drug, that specifically protects auditory fibers contributing to the coding of the temporal envelope and detection of tones in masking noise, tasks of our auditory senses, both of which, if they fail, lead to age-related speech-in-noise comprehension deficits.

Excessive daytime sleepiness, i.e., the inability to sustain wakefulness during the day, is a common Parkinson's disease (PD) non-motor symptom. Elevated cortico-basal ganglia beta oscillatory power (8-35 Hz) is a pathophysiological signature of PD motor signs. The relationship between beta oscillatory power and daytime sleepiness, however, remains unclear. Here, we examined the relationship between beta power and daytime vigilance in parkinsonian nonhuman primates. We administered dopaminergic medication to alter cortico-basal ganglia beta power and measured its effect on daytime vigilance. The beta power from motor cortex (MC) and subthalamic nucleus (STN), and wake quantity were derived in the following conditions: OFF-medication, ON-medication, and decay of medication effect. STN low-beta (8-20 Hz) power negatively correlated with wake quantity, suggesting that elevated STN low-beta power could disrupt sustenance of wakefulness. The cortical low-beta power did not correlate with wakefulness. Interestingly, STN and MC high-beta (21-35 Hz) power positively correlated with wake quantity. Our data provide evidence for an association between beta power and daytime vigilance in parkinsonism in addition to its known relationship with PD motor signs. These findings could inform targeted treatments to promote wakefulness in PD by selectively suppressing (e.g., low-beta) and/or amplifying (e.g., high-beta) cortico-basal ganglia beta oscillatory power.