LFP publications

Obective. Bipolar re-referencing (BPRR), in which one electrode’s signal is subtracted from a neighboring electrode to produce a differential signal, can improve signal readability and refine localization for intracranial electroencephalography. There is wide variation in manufactured electrode array spacing, yet how BPRR affects specific frequencies at precise inter-electrode distances has not been systematically evaluated. Approach. Intracranial recordings with uniquely large numbers of electrodes were obtained for sixteen patients with drug-resistant epilepsy. We evaluated combinations of high-density subdural grid, depth, and strip electrodes ( n = 3,664, 742, and 336) with manufactured linear inter-electrode distances of 4, 5, and 10 mm, respectively. BPRR was performed using all possible electrode pairs ( n = 445 305 grid, 16 004 depth, 3278 strip) spanning distances from 2–60 mm. Multi-taper power spectra were generated separately for grid, depth, and strip contacts. Distances were consolidated across patients and anatomical areas for generalizability, and distance-related influences on task-related brain activity and quantitative interictal epileptiform discharge localization were evaluated. Main results. We identified 8 mm as a consistent reversal point for BPRR, below which low-frequency signals (<30 Hz) had consistently decreased power, and higher frequencies had increased power. Larger distances increased all broadband (2–200 Hz) signals. Task-related increases in superior temporal gyrus 50–200 Hz activity were consistently enhanced across 4–40 mm bipolar distances. There were non-significant difference trends between 4 and 8 mm re-referencing on epileptiform discharge detection. Significance. BPRR distance imposed specific transition points for distance and frequency (roughly 8 mm and ∼30 Hz, respectively) that produced differential effects on measurements of signal power. The consistency across brain regions and electrode types (depth, subdural) suggests these influences are physical brain bio-signal properties, potentially related to spatial wavelength of periodic oscillations in lower frequencies in contrast to more aperiodic activity in higher frequencies. A distance-frequency relation map is provided to help optimize neural signal biomarker quality for intracranial applications by guiding strategic re-referencing distance selection.

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.

Persistent maladaptive drug-context associations are a key component of relapse vulnerability and pose a major obstacle in treating opioid use disorder. Although the dorsal hippocampus (dHPC) is critical for contextual memory formation, the synaptic mechanisms by which opioids alter hippocampal circuits to sustain these associations remain unclear. We previously found that repeated context-paired morphine exposure impairs dHPC long-term potentiation (LTP) through enhanced activity of small-conductance calcium-activated potassium (SK2) channels. Here, we investigated the role of SK2 channels in morphine-context associative learning and memory by combining in vivo electrophysiology, molecular analyses, and behavioral pharmacology with the morphine-conditioned place preference (MorCPP) paradigm in male mice. Manipulation of SK2 channels with either SK2 blocker Lei-Dab7 or activator NS309 before MorCPP post-test dose-dependently reduced MorCPP preference, despite no changes observed in SK2 mRNA or protein expression following MorCPP post-test. Interestingly, SK2 blockade during conditioning instead facilitated morphine-context memory formation, suggesting a distinct SK2 role in drug-context memory acquisition versus retrieval. Electrophysiology data suggest that modulation of dHPC neuronal activity by SK2 channels could be a potential mechanism underlying these observations. Our findings demonstrate that dHPC SK2 channels regulate morphine-context memory formation and retrieval, identifying them as a candidate for mitigating context-driven drug behaviors.

The thalamocortical pathways exhibit neuroplasticity not only during the critical period but also in adulthood. In this study, we investigated how cholecystokinin (CCK) modulates age-dependent thalamocortical plasticity. Our findings demonstrated that CCK is expressed in thalamocortical neurons and that high-frequency stimulation (HFS) of the thalamocortical pathway triggers the release of CCK in auditory cortex (ACx), as detected by a CCK sensor. HFS of the medial geniculate body (MGB) induced thalamocortical long-term potentiation (LTP) in wild-type young adult mice. However, knockdown of CCK expression in MGB neurons or blockade of the CCK-B receptor (CCKBR) in the ACx abolished HFS-induced LTP. Interestingly, this LTP could not be elicited in juvenile (3-week-old) or aged mice (over 18-month-old) due to distinct mechanisms: the absence of CCKBR in juveniles and the inability to release CCK in aged mice. Notably, exogenous administration of CCK into the ACx rescued LTP in aged mice and significantly improved frequency discrimination. These findings highlight the potential of CCK as a therapeutic intervention for ameliorating neuroplasticity deficits associated with thalamocortical connectivity.

During wake, sound‐evoked and spontaneous neural activity of the auditory cortex evolves in distinct subspaces, whereas anesthesia disrupts sound responses and merges these spaces. To evaluate if similar modifications of sound representation geometry explain sensory disconnection during sleep, large neural populations of the mouse auditory cortex are followed across slow‐wave sleep and wakefulness. It is observed that sleep dampens sound responses but preserves the geometry of sound representations such that they remain separate from spontaneous activity. Moreover, response dampening is strongly coordinated across neurons and varied throughout sleep, spanning from fully preserved response patterns to population response failures on a fraction of sound presentations. These failures rarely occurred in wakefulness and are more common during high spindle‐band activity. Therefore, in sleep, the auditory system preserves sound feature selectivity up to the cortex for detailed acoustic surveillance but concurrently implements an intermittent gating mechanism leading to local sensory disconnections.

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.

Impulsivity is a core pathological feature of various psychiatric disorders including obsessive‐compulsive disorder, attention‐deficit/hyperactivity disorder, and schizophrenia, which is conceptualized as dysregulated motivational and inhibitory processes. However, the underlying neural mechanism is poorly known. Using an olfactory cued Go/No‐Go task, this work finds increased false alarm rate, shortened licking onset latency, elevated licking frequency and reduced inter‐trial consistency in mice treated by the NMDAR antagonist (MK‐801). Fiber optic recordings reveal MK‐801 enhanced cue‐evoked neuronal responses in the olfactory bulb (OB), orbitofrontal cortex (OFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), while reducing reward‐predictive cue selectivity and increasing NAc dopamine release. Additionally, in vivo electrophysiological recordings demonstrate that theta oscillation power in the NAc and its coherence with OB, OFC, and VTA are also amplified. MK‐801 treatment enhances the correlation between firing rates of NAc neurons and cue, decreases the association with reward, strengthens the correlation with licking and increases the probability of firing peak preceding lick onset. Furthermore, this work confirms that the application of the trace amine‐associated receptor 1 agonist SEP‐363856 could correct the abnormal responses of NAc neurons and behavioral deficits. These findings elucidate the neural basis of impulsivity and support the potential therapeutic effect of SEP.

Human decision-making involves model-free and model-based reinforcement learning (RL) strategies, largely implemented by prefrontal-striatal circuits. Combining human brain imaging with neural network modelling in a probabilistic reversal learning task, we identify a unique role for the mediodorsal thalamus (MD) in arbitrating between RL strategies. While both dorsal PFC and the striatum support rule switching, the former does so when subjects predominantly adopt model-based strategy, and the latter model-free. The lateral and medial subdivisions of MD likewise engage these modes, each with distinct PFC connectivity. Notably, prefrontal transthalamic processing increases during the shift from stable rule use to model-based updating, with model-free updates at intermediate levels. Our CogLinks model shows that model-free strategies emerge when prefrontal-thalamic mechanisms for context inference fail, resulting in a slower overwriting of prefrontal strategy representations - a phenomenon we empirically validate with fMRI decoding analysis. These findings reveal how prefrontal transthalamic pathways implement flexible RL-based cognition.

Hydrogels have emerged as promising materials for anti‐fibrotic neural interfaces due to their mechanical and chemical similarity to biological tissue. However, their use in multimodal platforms remains limited, owing to fabrication challenges in microstructuring multiple functional hydrogels into compact architectures. Here, a hydrogel thermal drawing process (HG‐TDP) is presented that enables the co‐fabrication of multiple thermoplastically deformable hydrogels into a single, compact, and multifunctional fiber. By optimizing key process parameters, all‐hydrogel neural interfaces are developed that minimize gliosis through tissue‐like mechanical compliance and enable post‐implantation anti‐inflammatory drug delivery via the hydrogel‐based matrix. These fibers feature the compact integration of diverse hydrogel components, including a step‐index optical waveguide, an electrically conductive hydrogel electrode, and a hydrogel‐based microfluidic channel within a unified fiber structure. This integration enables multimodal neural interfacing, as demonstrated by high‐quality neural signal recording, optogenetic stimulation, and localized chemical modulation of neural circuits. This work offers a scalable route toward compact, fully hydrogel‐based neural interfaces that combine multimodal functionality with tissue‐friendly, anti‐fibrotic properties.

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.

Although clinical and experimental evidence highlight the role of the thalamus in voluntary movement production, the involvement of the thalamus in complex motor tasks such as speech production remains to be elucidated. The present study examined neural activity within the bilateral thalamus in 13 participants (seven females) with essential tremor undergoing awake deep brain stimulation implantation surgery, using three speech tasks of varied complexity [vowel vocalization, a diadochokinetic task (DDK), and sentence repetition]. Low-frequency neural activity (delta/theta band) activity was significantly increased during sentence and DDK compared with vowel vocalization in the bilateral motor thalamus and, to a lesser extent, increased for sentence repetition compared with DDK. Moreover, there was prominent prespeech beta band activity, with a greater decrease in the power of beta activity for sentence compared with DDK and vowel vocalization. The greater low-frequency activity in more complex speech tasks may reflect the allocation of additional cognitive resources to monitor the execution of speech motor plans through cortico–thalamo–cortical pathways in a temporally precise manner. The greater decrease in the power of beta activity prior to the onset of sentence repetition may imply greater involvement of the bilateral thalamus in the planning of complex speech tasks. These findings provide new insights into the role of the bilateral thalamus in speech production and may have clinical implications for neurological disorders that affect speech production.

Introduction The posterior tail of the striatum receives dense inputs from sensory regions of cortex and thalamus, as well as midbrain dopaminergic innervation, providing a neural substrate for associative sensory learning. Previously, we have demonstrated that developmental hearing loss is associated with aberrant physiological states in striatal medium spiny neurons (MSNs). Methods Here we directly investigated auditory associative learning impairments in the striatum of adult Mongolian gerbils that underwent transient developmental hearing loss or sham hearing loss during the critical period of auditory development. We used electrophysiology to reveal significant changes to neuronal population responses in vivo and intrinsic and synaptic properties to medium spiny neurons in vitro as animals learned an appetitive “Go/No-Go” auditory discrimination task. For in vivo experiments a 64-channel electrode was implanted in the auditory region of the posterior tail of the striatum and neuronal recordings were carried out as animals learned the task. For in vitro experiments, corticostriatal slice preparations were made from animals on each day of training. Results In naïve animals from both groups there was limited to no phase locking to either auditory stimulus in vivo , and long term depression resulted from theta burst stimulation in vitro . Furthermore, intrinsic and synaptic properties in normal hearing animals were unaffected; however, the hearing loss group continued to show lowered synaptic inhibition, synaptic hyperexcitation, and suppressed intrinsic excitability in the hearing loss group. Starting around day 3–4 in both groups, the emergence of striatal medium spiny neuron phase locking to the auditory conditioning stimuli was observed in vivo . This occurred contemporaneous to an increased probability of theta burst induced LTP during MSN whole cell recording in vitro , and acquisition of the task as the correct rejection response significantly increased in the behaving animals. During the acquisition phase MSNs in the normal hearing group showed a significant decrease in synaptic inhibition and increase in synaptic excitation with no change to intrinsic excitability, while the MSNs in the hearing loss group showed a significant increase in synaptic inhibition, reduction of synaptic hyper excitability, and compensatory changes to intrinsic excitability that supported normal action potential generation. In both groups, synaptic properties were resolved to similar level of E/I balance that could be part of a conserved learning state. Discussion These changes to the intrinsic and synaptic properties likely support LTP induction in vivo and the strengthening of synapses between auditory inputs and MSNs that facilitate neuronal phase locking. These findings have significant implications for our understanding of striatal resilience to sensory impairments in early life, in addition to establishing a granular understanding of the striatal circuit changes that support reward driven stimulus–response learning.

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment for dystonia, yet the neurophysiological mechanisms underlying frequency-dependent effects remain poorly understood. In this study, we investigate how different GPi-DBS frequencies modulate evoked potential (EP) characteristics within the basal ganglia-thalamo-cortical network in pediatric dystonia patients. We evaluated how increasing stimulation frequency alters EP morphology, focusing on peak-to-peak amplitude (PPa), peak-to-peak duration (PPd), and time to peak (TP). This analysis was motivated by clinical observations that higher DBS frequencies often produce distinct therapeutic effects, suggesting underlying differences in how neural circuits respond to varying stimulation rates. We analyzed intracranial electrophysiological recordings from 13 pediatric and young adult dystonia patients undergoing staged DBS implantation. EPs were recorded from the GPi and subthalamic nucleus (STN) of basal ganglia, and ventral oralis (VO) nucleus of the thalamus during unilateral GPi stimulation at 55, 85, 185, and 250 Hz. EP detection and characterization were performed using an automated algorithm, and group-level analyses were conducted using linear mixed effects models to assess frequency-dependent changes across regions. Increasing stimulation frequency significantly decreased PPa and increased PPd and TP, with a clear threshold effect: 55 Hz and 85 Hz produced similar responses, while 185 Hz and 250 Hz elicited significantly greater changes. These frequency-dependent effects were most pronounced in GPi recordings, followed by STN and VO, suggesting that local circuit dynamics are more sensitive to frequency modulation. Our findings highlight the distinct neurophysiological effects of DBS frequency on EP characteristics, emphasizing the need for personalized DBS programming. The pronounced frequency-dependent modulation observed in GPi suggests that optimal stimulation parameters should be tailored to the target region rather than applying uniform settings across patients. Future studies should investigate the clinical relevance of these EP dynamics and explore their potential as biomarkers for DBS optimization in dystonia.

Aging disrupts brain network integration and is a significant risk factor for cognitive decline and neurological diseases, yet the circuit-level mechanisms underlying these changes remain unclear. Most previous studies have utilized cross-sectional or acute approaches, limiting insights into the longitudinal dynamics of the neural network. In this study, we chronically recorded laminar electrophysiological activity in both the primary visual cortex (V1) and hippocampal CA1 region of young (2-month-old) and aged (13-month-old) mice over 16 weeks. This approach allowed us to directly assess how aging modulates functional connectivity within hierarchically connected cortical and hippocampal circuits. We found that single-unit spiking activity and the signal-to-noise ratio were largely preserved in aged versus young mice, suggesting intact neuronal firing properties. However, aged mice showed global reductions in local field potential (LFP) power and a selective decrease in coherence across delta, alpha-beta, and gamma frequency bands within and between cortical layers and V1-CA1 pathways, while phase amplitude coupling remained unaffected. Interestingly, population level excitatory activity in CA1 was increased in aged animals. These findings indicate that aging selectively impairs network-level synchrony and temporal coordination in specific frequency bands and regions, with minimal loss of single-neuron function. Our results highlight the necessity of longitudinal, multi-region measurements to uncover the multi-scale vulnerabilities of the aging brain. Understanding the depth- and region-dependent circuit changes will guide strategies to preserve cortical-hippocampal communication and cognitive function in aging, as well as enhance neural interface technologies for older populations. NEW & NOTEWORTHY Aging non-uniformly degrades cortico-hippocampal networks, leading to region- and frequency-specific breakdowns in coordinated activity. While single-neuron activity remains preserved, disruptions in frequency-selective synchrony (delta and alpha-beta) were observed in aged mice, indicating impaired V1-CA1 communication as a marker of aging rather than neuronal degeneration. By separating single-neuron activity and large-scale dynamics, we reveal that aging alters communication between sensory and memory systems, underscoring the need for longitudinal approaches to capture age-related impairments in laminar connectivity.

Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation reflect the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice (both male and female) expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway in awake, head-fixed mice, we presented ramp-and-hold light at different intensities while recording neural activity in the primary somatosensory barrel cortex (S1) and the ventral posteromedial nucleus (VPm) of the thalamus using silicon probes. We found that the activation of S1 L6CT neurons induces high-frequency LFP oscillations in S1 that are modulated in frequency, but not in amplitude, across light intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the temporal evolution of firing rate in S1 and VPm. While most S1 neurons were steadily suppressed, VPm and S1 layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to facilitated within 500 ms, suggesting differential recruitment of the intracortical versus cortico-thalamo-cortical pathways. Finally, we found that LFP frequency selectively correlates with VPm firing rate. Taken together, our data suggests that L6CT neurons sculpt the frequency of S1 LFP oscillations through cortico-thalamo-cortical circuits, linking the recurrent interactions mediated by L6CT neurons to the high gamma oscillations observed across physiological and pathological conditions.

Behavioral outcomes are rarely certain, requiring subjects to discriminate between available choices by using feedback to guide future decisions. Probabilistic reversal learning (PRL) tasks test subjects’ ability to learn and flexibly adapt to changes in reward contingencies. Cortico-striatal circuitry has been broadly implicated in flexible decision-making—though what role these circuits play remains complicated. In this study we leveraged the fast temporal dynamics of local field potentials to precisely identify the role that cortico-striatal networks play during PRL reward feedback. We measured widespread (32-CH) local field potential activity of male Long–Evans rats during a PRL task wherein a target response delivered reward on 80% of trials while a non-target response delivered reward on 20% of trials. When subjects learned those reward probabilities, contingencies were reversed. We found that reward-evoked oscillations at beta (15–30 Hz) and high gamma (>70 Hz) frequencies marked positive reward valence and reflected probability of reward. Activity and connectivity at beta frequencies between orbitofrontal cortex, anterior insula, medial prefrontal cortex, and ventral striatum during expected rewards were correlated with behavioral performance and specific aspects of value/exploitative behavior as defined by a reinforcement learning computational model. Finally, we found that modulating beta activity in orbitofrontal cortex with optogenetic (20 Hz) stimulation promoted maladaptive behavior when stimulation was provided during non-target responses, consistent with our data and computational model predictions. Reward-evoked beta oscillations may reflect a crucial component underlying reward learning, and erroneous elevations in this physiological signal may contribute to maladaptive task performance and behavioral disruptions.

Objectives Demonstrate proof‐of‐concept that superficial vibro‐tactile stimulation (VTS) of the larynx can serve as a non‐invasive neuromodulation method to reduce voice symptoms in people with abductor‐type laryngeal dystonia (ABLD) and record the underlying neural response to VTS of the somatosensory‐motor cortex. Methods Using a wearable collar with embedded vibrators, 11 people with ABLD received VTS for 24 min. To assess voice effects, they vocalized vowels and spoke standardized test sentences and words. Cortical activity was recorded using 64‐channel EEG. S moothed cepstral peak prominence , cumulative word and sentence duration were derived from voice recordings as objective markers of speech quality next to perceived speech effort as a subjective marker. Results In response to VTS, 64% of participants rated their improvement in voice quality as noticeable to very noticeable. Analysis of objective voice measures indicated a reduction in voice symptoms in up to 45% of participants immediately after and/or 20 min past the cessation of VTS. The cortical response to VTS application was a reduced event‐related spectral power in theta, alpha, and beta bands over left and right somatosensory‐motor cortical areas that was most prominent over the left premotor cortex in 7/11 participants. Conclusion Applying laryngeal VTS proved to be feasible and safe. VTS can induce acute short‐term reductions in voice symptoms, which is important given the limited therapeutic options for ABLD. The electrocortical correlate of VTS was an event‐related desynchronization of neuronal firing patterns over bilateral somatosensory‐motor cortex. Level of Evidence 4.

Glutamatergic neuronal activity promotes proliferation of both oligodendrocyte precursor cells (OPCs) and gliomas, including diffuse midline glioma (DMG). However, the role of neuromodulatory brainstem neurons projecting to midline structures where DMGs arise remains unexplored. Here, we demonstrate that midbrain cholinergic neuronal activity modulates OPC and DMG proliferation in a circuit-dependent manner. Optogenetic stimulation of the cholinergic pedunculopontine nucleus (PPN) promotes glioma growth in pons, while stimulation of the laterodorsal tegmentum nucleus (LDT) drives proliferation in thalamus. DMG-bearing mice exhibit higher acetylcholine release and increased cholinergic neuronal activity over the disease course. In co-culture, cholinergic neurons enhance DMG proliferation, and acetylcholine directly acts on DMG cells. Single-cell RNA sequencing revealed high CHRM1 and CHRM3 expression in primary DMG samples. Pharmacological or genetic blockade of M1/M3 receptors abolished cholinergic activity-driven DMG proliferation. Taken together, these findings demonstrate that midbrain cholinergic long-range projections promote activity-dependent DMG growth, mirroring a parallel proliferative effect on healthy OPCs.

Fragile X Syndrome (FXS) is a leading genetic cause of autism spectrum disorders (ASD)- associated behaviors, including sensory processing deficits. Sensory sensitivity and temporal processing deficits in the auditory domain will affect development of language and cognitive functions. The mouse model for FXS, Fmr1 KO, has shown remarkably similar auditory processing phenotypes to patients with FXS. In vitro cortical slice recordings show layer-specific differences in Fmr1 KO mouse local circuits, but it is unclear how these differences translate to changes in sensory processing. In this study, we used a depth multielectrode to record in vivo spikes and local field potentials across layers of the auditory cortex in Fmr1 KO and wildtype mice (WT), converting the latter to current source density (CSD) profiles for improved spatial resolution analysis. We observed reduced CSD sink amplitudes and inter-trial phase coherence, and an increase in trial-to-trial variability for temporally modulated stimuli in the KO mice. Results indicated a differential cortical layer pattern of activity in KO mice, with higher baseline gamma power in superficial and deep layers and higher resting delta and theta power in granular layers. Significantly elevated inter-trial variability was observed for CSD and spikes in KO mice. Auditory steady state responses to clicks or gaps at 40 Hz showed considerable trial-to-trial variability in a layer-specific manner in KO mice. Neural generators in the Fmr1 KO mouse auditory cortex failed to detect short gaps in noise, indicating severe temporal processing deficits. Altogether, this study indicates layer-specific cortical mechanisms of sensory hypersensitivity and temporal processing deficits in FXS.

The insular cortex is involved in a wide range of auditory functions in the mammalian brain. We studied the organization and basic response properties of auditory neurons in the insular cortex and adjacent areas by recording responses to sound stimuli in anesthetized female rats. Auditory neurons were present in an insulo-parietal auditory field that spans the boundary between the posterior insula, particularly in the granular insular cortex, and the ventral part of the adjacent nonprimary somatosensory fields. Confirming previous reports, neurons in this field had narrow tuning and were preferentially tuned to relatively low frequencies (<16 kHz). Intriguingly, auditory units in this field displayed shorter minimal latencies than units in the primary auditory cortex, as well as weaker sensitivity to deviance. These results establish the existence of a rapid auditory information stream with distinct properties through the insulo-parietal cortex that may parallel the pathway through the primary and anterior auditory fields.