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Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains unclear. Here, we used optogenetics-assisted circuit mapping to identify how multiple top-down inputs from higher-order cortical and thalamic areas engage V1 excitatory and inhibitory neurons. Top-down inputs overlap in superficial layers yet segregate in deep layers. Inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) converge on L6 Pyrs, whereas ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) inputs are processed in parallel in Pyr-type-specific subnetworks (Pyr ←ORBvl and Pyr ←LP ) and drive mutual inhibition between them via local interneurons. Our study deepens understanding of the top-down modulation mechanisms of visual processing and establishes that V2M and ACA inputs in L6 employ integrated processing distinct from the parallel processing of LP and ORBvl inputs in L5., (© 2024. The Author(s).)

Competing Interests: The authors declare no competing financial interests.

Consciousness can be conceptualized as varying along at least two dimensions: the global state of consciousness and the content of conscious experience. Here, we highlight the cellular and systems-level contributions of the thalamus to conscious state and then argue for thalamic contributions to conscious content, including the integrated, segregated, and continuous nature of our experience. We underscore vital, yet distinct roles for core- and matrix-type thalamic neurons. Through reciprocal interactions with deep-layer cortical neurons, matrix neurons support wakefulness and determine perceptual thresholds, whereas the cortical interactions of core neurons maintain content and enable perceptual constancy. We further propose that conscious integration, segregation, and continuity depend on the convergent nature of corticothalamic projections enabling dimensionality reduction, a thalamic reticular nucleus-mediated divisive normalization-like process, and sustained coherent activity in thalamocortical loops, respectively. Overall, we conclude that the thalamus plays a central topological role in brain structures controlling conscious experience., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver's biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST; N  = 234 humans, 137 female). We demonstrate that a sequence of simulated external thalamocortical and corticocortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in the effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The processing of sensory information, even at early stages, is influenced by the internal state of the animal. Internal states, such as arousal, are often characterized by relating neural activity to a single "level" of arousal, defined by a behavioral indicator such as pupil size. In this study, we expand the understanding of arousal-related modulations in sensory systems by uncovering multiple timescales of pupil dynamics and their relationship to neural activity. Specifically, we observed a robust coupling between spiking activity in the mouse dorsolateral geniculate nucleus (dLGN) of the thalamus and pupil dynamics across timescales spanning a few seconds to several minutes. Throughout all these timescales, 2 distinct spiking modes-individual tonic spikes and tightly clustered bursts of spikes-preferred opposite phases of pupil dynamics. This multi-scale coupling reveals modulations distinct from those captured by pupil size per se, locomotion, and eye movements. Furthermore, coupling persisted even during viewing of a naturalistic movie, where it contributed to differences in the encoding of visual information. We conclude that dLGN spiking activity is under the simultaneous influence of multiple arousal-related processes associated with pupil dynamics occurring over a broad range of timescales., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Crombie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Study Objectives: Sleep supports systems memory consolidation through the precise temporal coordination of specific oscillatory events during slow-wave sleep, i.e. the neocortical slow oscillations (SOs), thalamic spindles, and hippocampal ripples. Beneficial effects of sleep on memory are also observed in infants, although the contributing regions, especially hippocampus and frontal cortex, are immature. Here, we examined in rats the development of these oscillatory events and their coupling during early life., Methods: EEG and hippocampal local field potentials were recorded during sleep in male rats at postnatal days (PD)26 and 32, roughly corresponding to early (1-2 years) and late (9-10 years) human childhood, and in a group of adult rats (14-18 weeks, corresponding to ~22-29 years in humans)., Results: SO and spindle amplitudes generally increased from PD26 to PD32. In parallel, frontocortical EEG spindles increased in density and frequency, while changes in hippocampal ripples remained nonsignificant. The proportion of SOs co-occurring with spindles also increased from PD26 to PD32. Whereas parietal cortical spindles were phase-locked to the depolarizing SO-upstate already at PD26, over frontal cortex SO-spindle phase-locking emerged not until PD32. Co-occurrence of hippocampal ripples with spindles was higher during childhood than in adult rats, but significant phase-locking of ripples to the excitable spindle troughs was observed only in adult rats., Conclusions: Results indicate a protracted development of synchronized thalamocortical processing specifically in frontocortical networks (i.e. frontal SO-spindle coupling). However, synchronization within thalamocortical networks generally precedes synchronization of thalamocortical with hippocampal processing as reflected by the delayed occurrence of spindle-ripple phase-coupling., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective . Our goal is to decode firing patterns of single neurons in the left ventralis intermediate nucleus (Vim) of the thalamus, related to speech production, perception, and imagery. For realistic speech brain-machine interfaces (BMIs), we aim to characterize the amount of thalamic neurons necessary for high accuracy decoding. Approach . We intraoperatively recorded single neuron activity in the left Vim of eight neurosurgical patients undergoing implantation of deep brain stimulator or RF lesioning during production, perception and imagery of the five monophthongal vowel sounds. We utilized the Spade decoder, a machine learning algorithm that dynamically learns specific features of firing patterns and is based on sparse decomposition of the high dimensional feature space. Main results . Spade outperformed all algorithms compared with, for all three aspects of speech: production, perception and imagery, and obtained accuracies of 100%, 96%, and 92%, respectively (chance level: 20%) based on pooling together neurons across all patients. The accuracy was logarithmic in the amount of neurons for all three aspects of speech. Regardless of the amount of units employed, production gained highest accuracies, whereas perception and imagery equated with each other. Significance . Our research renders single neuron activity in the left Vim a promising source of inputs to BMIs for restoration of speech faculties for locked-in patients or patients with anarthria or dysarthria to allow them to communicate again. Our characterization of how many neurons are necessary to achieve a certain decoding accuracy is of utmost importance for planning BMI implantation., (Creative Commons Attribution license.)

The superior colliculus receives powerful synaptic inputs from corticotectal neurons in the visual cortex. The function of these corticotectal neurons remains largely unknown due to a limited understanding of their response properties and connectivity. Here, we use antidromic methods to identify corticotectal neurons in awake male and female rabbits, and measure their axonal conduction times, thalamic inputs and receptive field properties. All corticotectal neurons responded to sinusoidal drifting gratings with a nonlinear (nonsinusoidal) increase in mean firing rate but showed pronounced differences in their ON-OFF receptive field structures that we classified into three groups, Cx, S2, and S1. Cx receptive fields had highly overlapping ON and OFF subfields as classical complex cells, S2 had largely separated ON and OFF subfields as classical simple cells, and S1 had a single ON or OFF subfield. Thus, all corticotectal neurons are homogeneous in their nonlinear spatial summation but very heterogeneous in their spatial integration of ON and OFF inputs. The Cx type had the fastest conducting axons, the highest spontaneous activity, and the strongest and fastest visual responses. The S2 type had the highest orientation selectivity, and the S1 type had the slowest conducting axons. Moreover, our cross-correlation analyses found that a subpopulation of corticotectal neurons with very fast conducting axons and high spontaneous firing rates (largely "Cx" type) receives monosynaptic input from retinotopically aligned thalamic neurons. This previously unrecognized fast-conducting thalamic-mediated corticotectal pathway may provide specialized information to superior colliculus and prime recipient neurons for subsequent corticotectal or retinal synaptic input., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Objective. Beta triggered closed-loop deep brain stimulation (DBS) shows great potential for improving the efficacy while reducing side effect for Parkinson's disease. However, there remain great challenges due to the dynamics and stochasticity of neural activities. In this study, we aimed to tune the amplitude of beta oscillations with different time scales taking into account influence of inherent variations in the basal ganglia-thalamus-cortical circuit. Approach . A dynamic basal ganglia-thalamus-cortical mean-field model was established to emulate the medication rhythm. Then, a dynamic target model was designed to embody the multi-timescale dynamic of beta power with milliseconds, seconds and minutes. Moreover, we proposed a closed-loop DBS strategy based on a proportional-integral-differential (PID) controller with the dynamic control target. In addition, the bounds of stimulation amplitude increments and different parameters of the dynamic target were considered to meet the clinical constraints. The performance of the proposed closed-loop strategy, including beta power modulation accuracy, mean stimulation amplitude, and stimulation variation were calculated to determine the PID parameters and evaluate neuromodulation performance in the computational dynamic mean-field model. Main results . The Results show that the dynamic basal ganglia-thalamus-cortical mean-field model simulated the medication rhythm with the fasted and the slowest rate. The dynamic control target reflected the temporal variation in beta power from milliseconds to minutes. With the proposed closed-loop strategy, the beta power tracked the dynamic target with a smoother stimulation sequence compared with closed-loop DBS with the constant target. Furthermore, the beta power could be modulated to track the control target under different long-term targets, modulation strengths, and bounds of the stimulation increment. Significance . This work provides a new method of closed-loop DBS for multi-timescale beta power modulation with clinical constraints., (© 2024 IOP Publishing Ltd.)

Information flow in brain networks is reflected in local field potentials that have both periodic and aperiodic components. The 1/fχ aperiodic component of the power spectra tracks arousal and correlates with other physiological and pathophysiological states. Here we explored the aperiodic activity in the human thalamus and basal ganglia in relation to simultaneously recorded cortical activity. We elaborated on the parameterization of the aperiodic component implemented by specparam (formerly known as FOOOF) to avoid parameter unidentifiability and to obtain independent and more easily interpretable parameters. This allowed us to seamlessly fit spectra with and without an aperiodic knee, a parameter that captures a change in the slope of the aperiodic component. We found that the cortical aperiodic exponent χ, which reflects the decay of the aperiodic component with frequency, is correlated with Parkinson's disease symptom severity. Interestingly, no aperiodic knee was detected from the thalamus, the pallidum, or the subthalamic nucleus, which exhibited an aperiodic exponent significantly lower than in cortex. These differences were replicated in epilepsy patients undergoing intracranial monitoring that included thalamic recordings. The consistently lower aperiodic exponent and lack of an aperiodic knee from all subcortical recordings may reflect cytoarchitectonic and/or functional differences., Significance Statement: The aperiodic component of local field potentials can be modeled to produce useful and reproducible indices of neural activity. Here we refined a widely used phenomenological model for extracting aperiodic parameters (namely the exponent, offset and knee), with which we fit cortical, basal ganglia, and thalamic intracranial local field potentials, recorded from unique cohorts of movement disorders and epilepsy patients. We found that the aperiodic exponent in motor cortex is higher in Parkinson's disease patients with more severe motor symptoms, suggesting that aperiodic features may have potential as electrophysiological biomarkers for movement disorders symptoms. Remarkably, we found conspicuous differences in the aperiodic parameters of basal ganglia and thalamic signals compared to those from neocortex., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The thalamic reuniens (Re) and rhomboid (Rh) nuclei are bidirectionally connected with the medial prefrontal cortex (mPFC) and the hippocampus (Hip). Fiber-sparing N-methyl-D-aspartate lesions of the ReRh disrupt cognitive functions, including persistence of certain memories. Because such lesions irremediably damage neurons interconnecting the ReRh with the mPFC and the Hip, it is impossible to know if one or both pathways contribute to memory persistence. Addressing such an issue requires selective, pathway-restricted and direction-specific disconnections., New Method: A recent method associates a retrograde adeno-associated virus (AAV) expressing Cre recombinase with an anterograde AAV expressing a Cre-dependent caspase, making such disconnection feasible by caspase-triggered apoptosis when both constructs meet intracellularly. We injected an AAVrg-Cre-GFP into the ReRh and an AAV5-taCasp into the mPFC. As expected, part of mPFC neurons died, but massive neurotoxicity of the AAVrg-Cre-GFP was found in ReRh, contrasting with normal density of DAPI staining. Other stainings demonstrated increasing density of reactive astrocytes and microglia in the neurodegeneration site., Comparison With Existing Methods: Reducing the viral titer (by a 4-fold dilution) and injection volume (to half) attenuated toxicity substantially, still with evidence for partial disconnection between mPFC and ReRh., Conclusions: There is an imperative need to verify potential collateral damage inherent in this type of approach, which is likely to distort interpretation of experimental data. Therefore, controls allowing to distinguish collateral phenotypic effects from those linked to the desired disconnection is essential. It is also crucial to know for how long neurons expressing the Cre-GFP protein remain operational post-infection., Competing Interests: Declaration of Competing Interest none. Conflict of interest The authors have no conflict of interest to declare. Declaration of Generative (AI) and AI-assisted technologies in the Writing Process. No such technologies have been used in the writing process., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Word finding difficulty is a frequent complaint in older age and disease states, but treatment options are lacking for such verbal retrieval deficits. Better understanding of the neurophysiological and neuroanatomical basis of verbal retrieval function may inform effective interventions. In this article, we review the current evidence of a neural retrieval circuit central to verbal production, including words and semantic memory, that involves the pre-supplementary motor area (pre-SMA), striatum (particularly caudate nucleus), and thalamus. We aim to offer a modified neural circuit framework expanded upon a memory retrieval model proposed in 2013 by Hart et al., as evidence from electrophysiological, functional brain imaging, and noninvasive electrical brain stimulation studies have provided additional pieces of information that converge on a shared neural circuit for retrieval of memory and words. We propose that both the left inferior frontal gyrus and fronto-polar regions should be included in the expanded circuit. All these regions have their respective functional roles during verbal retrieval, such as selection and inhibition during search, initiation and termination of search, maintenance of co-activation across cortical regions, as well as final activation of the retrieved information. We will also highlight the structural connectivity from and to the pre-SMA (e.g., frontal aslant tract and fronto-striatal tract) that facilitates communication between the regions within this circuit. Finally, we will discuss how this circuit and its correlated activity may be affected by disease states and how this circuit may serve as a novel target engagement for neuromodulatory treatment of verbal retrieval deficits., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: While the exploration of serotonergic psychedelics as psychiatric medicines deepens, so does the pressure to better understand how these compounds act on the brain., Methods: We used a double-blind, placebo-controlled, crossover design and administered lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), and d-amphetamine in 25 healthy participants. By using spectral dynamic causal modeling, we mapped substance-induced changes in effective connectivity between the thalamus and different cortex types (unimodal vs. transmodal) derived from a previous study with resting-state functional magnetic resonance imaging data. Due to the distinct pharmacological modes of action of the 3 substances, we were able to investigate specific effects mainly driven by different neurotransmitter systems on thalamocortical and corticothalamic interactions., Results: Compared with placebo, all 3 substances increased the effective connectivity from the thalamus to specific unimodal cortices, whereas the influence of these cortices on the thalamus was reduced. These results indicate increased bottom-up and decreased top-down information flow between the thalamus and some unimodal cortices. However, for the amphetamines, we found the opposite effects when examining the effective connectivity with transmodal cortices, including parts of the salience network. Intriguingly, LSD increased the effective connectivity from the thalamus to both unimodal and transmodal cortices, indicating a breach in the hierarchical organization of ongoing brain activity., Conclusions: The results advance our knowledge about the action of psychedelics on the brain and refine current models aiming to explain the underlying neurobiological processes., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The cerebellum has the reputation of being a primitive part of the brain that mostly is involved in motor coordination and motor control. Older lesion studies and more recent electrophysiological studies have, however, indicated that it is involved in temporal perception and temporal expectation building. An outstanding question is whether this temporal expectation building cerebellar activity has functional relevance. In this study, we collected magnetoencephalographic data from 30 healthy participants performing a detection task on at-threshold stimulation that was presented at the end of a sequence of temporally regular or irregular above-threshold stimulation. We found that behavioral detection rates depended on the degree of irregularity in the sequence preceding it. We also found cerebellar responses evoked by above-threshold and at-threshold stimulation. The evoked responses to at-threshold stimulation differed significantly, depending on whether it was preceded by a regular or an irregular sequence. Finally, we found that detection performance across participants correlated significantly with the differences in cerebellar evoked responses to the at-threshold stimulation, demonstrating the functional relevance of cerebellar activity in sensory expectation building. We furthermore found evidence of thalamic involvement, as indicated by responses in the beta band (14-30 Hz) and by significant modulations of cerebello-thalamic connectivity by the regularity of the sequence and the kind of stimulation terminating the sequence. These results provide evidence that the temporal expectation building mechanism of the cerebellum, what we and others have called an internal clock, shows functional relevance by regulating behavior and performance in sensory action that requires acting and integrating evidence over precise timescales., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Andersen and Dalal.)

The feedback projections from cortical layer 6 (L6CT) to the sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventral posteromedial nucleus of the thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons' firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions., (© 2024. The Author(s).)

Thalamocortical loops have a central role in cognition and motor control, but precisely how they contribute to these processes is unclear. Recent studies showing evidence of plasticity in thalamocortical synapses indicate a role for the thalamus in shaping cortical dynamics through learning. Since signals undergo a compression from the cortex to the thalamus, we hypothesized that the computational role of the thalamus depends critically on the structure of corticothalamic connectivity. To test this, we identified the optimal corticothalamic structure that promotes biologically plausible learning in thalamocortical synapses. We found that corticothalamic projections specialized to communicate an efference copy of the cortical output benefit motor control, while communicating the modes of highest variance is optimal for working memory tasks. We analyzed neural recordings from mice performing grasping and delayed discrimination tasks and found corticothalamic communication consistent with these predictions. These results suggest that the thalamus orchestrates cortical dynamics in a functionally precise manner through structured connectivity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system., (© 2024. The Author(s).)

Spindle-shaped waves of oscillations emerge in EEG scalp recordings during human and rodent non-REM sleep. The association of these 10-16 Hz oscillations with events during prior wakefulness suggests a role in memory consolidation. Human and rodent depth electrodes in the brain record strong spindles throughout the cortex and hippocampus, with possible origins in the thalamus. However, the source and targets of the spindle oscillations from the hippocampus are unclear. Here, we employed an in vitro reconstruction of four subregions of the hippocampal formation with separate microfluidic tunnels for single axon communication between subregions assembled on top of a microelectrode array. We recorded spontaneous 400-1000 ms long spindle waves at 10-16 Hz in single axons passing between subregions as well as from individual neurons in those subregions. Spindles were nested within slow waves. The highest amplitudes and most frequent occurrence suggest origins in CA3 neurons that send feed-forward axons into CA1 and feedback axons into DG. Spindles had 50-70% slower conduction velocities than spikes and were not phase-locked to spikes suggesting that spindle mechanisms are independent of action potentials. Therefore, consolidation of declarative-cognitive memories in the hippocampus may be separate from the more easily accessible consolidation of memories related to thalamic motor function., (© 2024. The Author(s).)

Local Field Potential (LFP), despite its name, often reflects remote activity. Depending on the orientation and synchrony of their sources, both oscillations and more complex waves may passively spread in brain tissue over long distances and be falsely interpreted as local activity at such distant recording sites. Here we show that the whisker-evoked potentials in the thalamic nuclei are of local origin up to around 6 ms post stimulus, but the later (7-15 ms) wave is overshadowed by a negative component reaching from cortex. This component can be analytically removed and local thalamic LFP can be recovered reliably using Current Source Density analysis. We used model-based kernel CSD (kCSD) method which allowed us to study the contribution of local and distant currents to LFP from rat thalamic nuclei and barrel cortex recorded with multiple, non-linear and non-regular multichannel probes. Importantly, we verified that concurrent recordings from the cortex are not essential for reliable thalamic CSD estimation. The proposed framework can be used to analyze LFP from other brain areas and has consequences for general LFP interpretation and analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Średniawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Deep brain stimulation (DBS) is an effective treatment for movement disorders, including Parkinson disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei-including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr), and ventral intermediate nucleus (Vim)-across different DBS frequencies., Materials and Methods: Both synthetic and experimental data were used in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work, and the experimental data were provided using single-unit microelectrode recordings (MERs) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr, and Vim-across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies., Results: Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies., Conclusions: The result of our model fitting was in agreement with experimental single-unit MER data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS and to potentially optimize stimulation parameters based on their actual effects on neuronal activity., Competing Interests: Conflict of Interest Suneil K. Kalia reports consulting fees from Boston Scientific, Medtronic, and Abbott. Andres M. Lozano reports consulting fees from Abbott, Boston Scientific, Medtronic, and Insightec. The remaining authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiology, and radiology to summarize the current state-of-the-art in DBS for ET. We explore the role of the thalamus in motor function and describe how differences in parcellations and nomenclature have shaped our understanding of the neuroanatomical substrates associated with optimal outcomes. Subsequently, we discuss how seminal studies have propagated the ventral intermediate nucleus (Vim)-centric view of DBS effects and shaped the ongoing debate over thalamic DBS versus stimulation in the posterior subthalamic area (PSA) in ET. We then describe probabilistic- and network-mapping studies instrumental in identifying the local and network substrates subserving tremor control, which suggest that the PSA is the optimal DBS target for tremor suppression in ET. Taken together, DBS offers promising outcomes for ET, with the PSA emerging as a better target for suppression of tremor symptoms. While advanced imaging techniques have substantially improved the identification of anatomical targets within this region, uncertainties persist regarding the distinct anatomical substrates involved in optimal tremor control. Inconsistent subdivisions and nomenclature of motor areas and other subdivisions in the thalamus further obfuscate the interpretation of stimulation results. While loss of benefit and habituation to DBS remain challenging in some patients, refined DBS techniques and closed-loop paradigms may eventually overcome these limitations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guenther Deuschl reports a relationship with Boston Scientific Corp that includes: consulting or advisory. Guenther Deuschl reports a relationship with Cavion that includes: consulting or advisory. Guenther Deuschl reports a relationship with Functional Neuromodulation that includes: consulting or advisory. Guenther Deuschl reports a relationship with Thieme Medical Publishers that includes: consulting or advisory. Andreas Horn reports a relationship with German Research Foundation that includes: funding grants. Andreas Horn reports a relationship with Deutsches Zentrum für Luft-und Raumfahrt that includes: funding grants., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Swallowing is a sophisticated process involving the precise and timely coordination of the central and peripheral nervous systems, along with the musculatures of the oral cavity, pharynx, and airway. The role of the infratentorial neural structure, including the swallowing central pattern generator and cranial nerve nuclei, has been described in greater detail compared with both the cortical and subcortical neural structures. Nonetheless, accumulated data from analysis of swallowing performance in patients with different neurological diseases and conditions, along with results from neurophysiological studies of normal swallowing have gradually enhanced understanding of the role of cortical and subcortical neural structures in swallowing, potentially leading to the development of treatment modalities for patients suffering from dysphagia. This review article summarizes findings about the role of both cortical and subcortical neural structures in swallowing based on results from neurophysiological studies and studies of various neurological diseases. In sum, cortical regions are mainly in charge of initiation and coordination of swallowing after receiving afferent information, while subcortical structures including basal ganglia and thalamus are responsible for movement control and regulation during swallowing through the cortico-basal ganglia-thalamo-cortical loop. This article also presents how cortical and subcortical neural structures interact with each other to generate the swallowing response. In addition, we provided the updated evidence about the clinical applications and efficacy of neuromodulation techniques, including both non-invasive brain stimulation and deep brain stimulation on dysphagia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation in tremor patients. Despite its therapeutic importance, its oscillatory coupling to cortical areas has rarely been investigated in humans., Objectives: The objective of this study was to identify the cortical areas coupled to the VIM in patients with essential tremor., Methods: We combined resting-state magnetoencephalography with local field potential recordings from the VIM of 19 essential tremor patients. Whole-brain maps of VIM-cortex coherence in several frequency bands were constructed using beamforming and compared with corresponding maps of subthalamic nucleus (STN) coherence based on data from 19 patients with Parkinson's disease. In addition, we computed spectral Granger causality., Results: The topographies of VIM-cortex and STN-cortex coherence were very similar overall but differed quantitatively. Both nuclei were coupled to the ipsilateral sensorimotor cortex in the high-beta band; to the sensorimotor cortex, brainstem, and cerebellum in the low-beta band; and to the temporal cortex, brainstem, and cerebellum in the alpha band. High-beta coherence to sensorimotor cortex was stronger for the STN (P = 0.014), whereas low-beta coherence to the brainstem was stronger for the VIM (P = 0.017). Although the STN was driven by cortical activity in the high-beta band, the VIM led the sensorimotor cortex in the alpha band., Conclusions: Thalamo-cortical coupling is spatially and spectrally organized. The overall similar topographies of VIM-cortex and STN-cortex coherence suggest that functional connections are not necessarily unique to one subcortical structure but might reflect larger frequency-specific networks involving VIM and STN to a different degree. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: A hallmark of migraine is photophobia. In mice, photophobia‐like behavior is induced by calcitonin gene‐related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. Design: We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and acute CGRP injections in wild‐type mice. Since the light/dark assay has historically been used to investigate anxiety‐like responses in animals, we measured anxiety in a light‐independent open field assay and asked if stimulation of a brain region, the periaqueductal gray, that induces anxiety would yield similar results to posterior thalamic stimulation. The hippocampus was used as an anatomical control to ensure that light‐aversive behaviors could not be induced by the stimulation of any brain region. Results: Optogenetic activation of neuronal cell bodies in the posterior thalamic nuclei elicited light aversion in both bright and dim light without an anxiety‐like response in an open field assay. Injection of CGRP into the posterior thalamic region triggered similar light‐aversive behavior without anxiety. In contrast to the posterior thalamic nuclei, optogenetic stimulation of dorsal periaqueductal gray cell bodies caused both light aversion and an anxiety‐like response, while CGRP injection had no effect. In the dorsal hippocampus, neither optical stimulation nor CGRP injection affected light aversion or open field behaviors. Conclusion: Stimulation of posterior thalamic nuclei is able to initiate light‐aversive signals in mice that may be modulated by CGRP to cause photophobia in migraine. [ABSTRACT FROM AUTHOR]

Objectives Numerous studies show benefits of mid- and late-life activity on neurocognitive health. Yet, few studies have examined how engagement in enriching activities during childhood, when the brain is most plastic, may confer long-term neurocognitive benefits that may be especially important to individuals raised in low-income settings. We examined associations between enriching early-life activities (EELAs) and hippocampal and amygdala volumes in a sample of predominantly African-American, community-dwelling older adults. We further assessed whether these associations were independent of current activity engagement. Methods Ninety participants from the baseline Brain Health Substudy of the Baltimore Experience Corps Trial (mean age: 67.4) completed retrospective activity inventories and an magnetic resonance imaging scan. Volumes were segmented using FreeSurfer. Results Each additional EELA was associated with a 2.3% (66.6 mm3) greater amygdala volume after adjusting for covariates. For men, each additional EELA was associated with a 4.1% (278.9 mm3) greater hippocampal volume. Associations were specific to these regions when compared with the thalamus, used as a control region. Discussion Enriching lifestyle activities during an important window of childhood brain development may be a modifiable factor that impacts lifelong brain reserve, and results highlight the importance of providing access to such activities in historically underserved populations. [ABSTRACT FROM AUTHOR]

Objectives: Tourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements.Methods: The data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants.Results: Recordings collected from the CM thalamic nucleus revealed a low-frequency power (3-10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements.Conclusion: We conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach. [ABSTRACT FROM AUTHOR]

Objective: The thalamus plays a major role in regulating arousal, consciousness, and activity. Distinct vascular distribution of the thalamus causes different syndromic presentations of thalamic nuclei infarctions. During the evaluation of acute thalamic infarction, it is important to determine the thalamic vascular zone that is affected. This study aimed to assess the topography of acute isolated unilateral thalamic infarction on diffusionweighted imaging, and to investigate the distribution of classic and variant type thalamic infarctions. Methods: The imaging database of the 336 consecutive patients with acute thalamic infarction admitted to the radiology department between January 2015 and February 2020 were retrospectively reviewed. Specifically, patients with acute isolated unilateral thalamic infarction were included. The most affected thalamic territory, variant/classical territory rates, and the comparison of age and gender were evaluated. Results: A total of 141 patients (classic territory group: 104, variant territory group: 37) were reviewed. The ratio of affected classic territory to variant territory was 2.8. Affected classic territories were inferolateral (n=68), anterior (n=25), paramedian (n=11), and posterior (n=0). Affected variant territories were posterolateral (n=18), central (n=13), and anteromedian (n=6). Comparing the patients in both groups, age, sex, and side were similar, p=0.435, p=0.71, and p=0.85, respectively. Relevant arteries did not have stenosis in 96.2% of patients, and no significant difference was observed between both groups, p=0.631. Conclusion: In isolated acute unilateral thalamic ischemia, the ratio of the affected variant to the classic territory was approximately 1/3. Therefore, during the radiologic evaluation of acute thalamic ischemia, a variant thalamic territory should be considered in the presence of infarction that does not fit the classic territory, in order to avoid clinical-radiological discrepancies. [ABSTRACT FROM AUTHOR]

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels. [ABSTRACT FROM AUTHOR]

Introduction: Executive dysfunction is common in dementia with Lewy bodies (DLB). The pulvinar nucleus plays a role in executive control and synchronizes with cortical regions in the salience network that are vulnerable to Lewy pathology. Objective: We investigated the pulvinar subregions in patients with mild DLB and their associations with executive function. Methods: The sample consisted of 38 DLB patients and 38 age- and sex-matched normal controls. We evaluated cognitive function using the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. We obtained four pulvinar nuclei using preprocessed T1-weighted magnetic resonance images. We compared volumes and textures of the DLB patients and the normal controls for each nucleus. We used a linear regression to determine the association of textures and neuropsychological test scores. Results: The DLB patients showed comparable volumes to the normal controls in all pulvinar nuclei. However, the DLB patients showed different texture of the left medial pulvinar (PuM) from the normal controls. The entropy, contrast, and cluster shade were lower but autocorrelation of left PuM was higher in the DLB patients compared to the normal controls. These texture features of the left PuM were associated with the set-shifting performance measured by the Trail Making Test. Conclusions: In DLB, the left PuM may be altered from early stage, which may contribute to the development of executive dysfunction. [ABSTRACT FROM AUTHOR]

Direct imaging of neuronal activity (DIANA) by functional magnetic resonance imaging (fMRI) could be a revolutionary approach for advancing systems neuroscience research. To independently replicate this observation, we performed fMRI experiments in anesthetized mice. The blood oxygenation level-dependent (BOLD) response to whisker stimulation was reliably detected in the primary barrel cortex before and after DIANA experiments; however, no DIANA-like fMRI peak was observed in individual animals' data with the 50 to 300 trials. Extensively averaged data involving 1050 trials in six mice showed a flat baseline and no detectable neuronal activity-like fMRI peak. However, spurious, nonreplicable peaks were found when using a small number of trials, and artifactual peaks were detected when some outlier-like trials were excluded. Further, no detectable DIANA peak was observed in the BOLD-responding thalamus from the selected trials with the neuronal activity-like reference function in the barrel cortex. Thus, we were unable to replicate the previously reported results without data preselection.

The nature of spinal output pathways that convey nociceptive information to the brain has been the subject of controversy. Here, we provide anatomical, molecular, and functional characterizations of two distinct anterolateral pathways: one, ascending in the lateral spinal cord, triggers nociceptive behaviors, and the other one, ascending in the ventral spinal cord, when inhibited, leads to sensorimotor deficits. Moreover, the lateral pathway consists of at least two subtypes. The first is a contralateral pathway that extends to the periaqueductal gray (PAG) and thalamus; the second is a bilateral pathway that projects to the bilateral parabrachial nucleus (PBN). Finally, we present evidence showing that activation of the contralateral pathway is sufficient for defensive behaviors such as running and freezing, whereas the bilateral pathway is sufficient for attending behaviors such as licking and guarding. This work offers insight into the complex organizational logic of the anterolateral system in the mouse., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information., (© 2024. The Author(s).)

Executive control, the ability to organize thoughts and action plans in real time, is a defining feature of higher cognition. Classical theories have emphasized cortical contributions to this process, but recent studies have reinvigorated interest in the role of the thalamus. Although it is well established that local thalamic damage diminishes cognitive capacity, such observations have been difficult to inform functional models. Recent progress in experimental techniques is beginning to enrich our understanding of the anatomical, physiological, and computational substrates underlying thalamic engagement in executive control. In this review, we discuss this progress and particularly focus on the mediodorsal thalamus, which regulates the activity within and across frontal cortical areas. We end with a synthesis that highlights frontal thalamocortical interactions in cognitive computations and discusses its functional implications in normal and pathological conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Multisensory integration is necessary for the animal to survive in the real world. While conventional methods have been extensively used to investigate the multisensory integration process in various brain areas, its long-range interactions remain less explored. In this study, our goal was to investigate interactions between visual and somatosensory networks on a whole-brain scale using 15.2-T BOLD fMRI. We compared unimodal to bimodal BOLD fMRI responses and dissected potential cross-modal pathways with silencing of primary visual cortex (V1) by optogenetic stimulation of local GABAergic neurons. Our data showed that the influence of visual stimulus on whisker activity is higher than the influence of whisker stimulus on visual activity. Optogenetic silencing of V1 revealed that visual information is conveyed to whisker processing via both V1 and non-V1 pathways. The first-order ventral posteromedial thalamic nucleus (VPM) was functionally affected by non-V1 sources, while the higher-order posterior medial thalamic nucleus (POm) was predominantly modulated by V1 but not non-V1 inputs. The primary somatosensory barrel field (S1BF) was influenced by both V1 and non-V1 inputs. These observations provide valuable insights for into the integration of whisker and visual sensory information., (© 2024. The Author(s).)

First-order thalamic nuclei receive feedforward signals from peripheral receptors and relay these signals to primary sensory cortex. Primary sensory cortex, in turn, provides reciprocal feedback to first-order thalamus. Because the vast majority of sensory thalamocortical inputs target primary sensory cortex, their complementary corticothalamic neurons are assumed to be similarly restricted to primary sensory cortex. We upend this assumption by characterizing morphologically diverse neurons in multiple mid-level visual cortical areas of the primate ( Macaca mulatta ) brain that provide direct feedback to the primary visual thalamus, the dorsal lateral geniculate nucleus (LGN). Although the majority of geniculocortical neurons project to primary visual cortex (V1), a minority, located mainly in the koniocellular LGN layers, provide direct input to extrastriate visual cortex. These "V1-bypassing" projections may be implicated in blindsight. We hypothesized that geniculocortical inputs directly targeting extrastriate cortex should be complemented by reciprocal corticogeniculate circuits. Using virus-mediated circuit tracing, we discovered corticogeniculate neurons throughout three mid-level extrastriate areas: MT, MST, and V4. Quantitative morphological analyses revealed nonuniform distributions of unique cell types across areas. Many extrastriate corticogeniculate neurons had spiny stellate morphology, suggesting possible targeting of koniocellular LGN layers. Importantly though, multiple morphological types were observed across areas. Such morphological diversity could suggest parallel streams of V1-bypassing corticogeniculate feedback at multiple stages of the visual processing hierarchy. Furthermore, the presence of corticogeniculate neurons across visual cortex necessitates a reevaluation of the LGN as a hub for visual information rather than a simple relay., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Adusei et al.)

Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals., Competing Interests: Competing interests statement:The authors declare no competing interest.

Failure in behavioral suppression is a key feature in substance use disorders, potentially leading to compulsive drug seeking and relapse. In this issue of Neuron, Paniccia et al. 1 elucidated a heroin-damaged paraventricular nucleus of the thalamus (PVT)-accumbal circuit and how recovery of PVT function could prevent heroin relapse., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The deepest layer of the cortex (layer 6b [L6b]) contains relatively few neurons, but it is the only cortical layer responsive to the potent wake-promoting neuropeptide orexin/hypocretin. Can these few neurons significantly influence brain state? Here, we show that L6b-photoactivation causes a surprisingly robust enhancement of attention-associated high-gamma oscillations and population spiking while abolishing slow waves in sleep-deprived mice. To explain this powerful impact on brain state, we investigated L6b's synaptic output using optogenetics, electrophysiology, and monoCaTChR ex vivo. We found powerful output in the higher-order thalamus and apical dendrites of L5 pyramidal neurons, via L1a and L5a, as well as in superior colliculus and L6 interneurons. L6b subpopulations with distinct morphologies and short- and long-term plasticities project to these diverse targets. The L1a-targeting subpopulation triggered powerful NMDA-receptor-dependent spikes that elicited burst firing in L5. We conclude that orexin/hypocretin-activated cortical neurons form a multifaceted, fine-tuned circuit for the sustained control of the higher-order thalamocortical system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) of the thalamus can effectively reduce tics in severely affected patients with Tourette syndrome (TS). Its effect on cortical oscillatory activity is currently unknown., Objective: We assessed whether DBS modulates beta activity at fronto-central electrodes. We explored concurrent EEG sources and probabilistic stimulation maps., Methods: Resting state EEG of TS patients treated with thalamic DBS was recorded in repeated DBS-on and DBS-off states. A mixed linear model was employed for statistical evaluation. EEG sources were estimated with eLORETA. Thalamic probabilistic stimulation maps were obtained by assigning beta power difference scores (DBS-on minus DBS-off) to stimulation sites., Results: We observed increased beta power in DBS-on compared to DBS-off states. Modulation of cortical beta activity was localized to the midcingulate cortex. Beta modulation was more pronounced when stimulating the thalamus posteriorly, peaking in the ventral posterior nucleus., Conclusion: Thalamic DBS in TS patients modulates beta frequency oscillations presumably important for sensorimotor function and relevant to TS pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The influence of novelty on feeding behavior is significant and can override both homeostatic and hedonic drives due to the uncertainty of potential danger. Previous work found that novel food hypophagia is enhanced in a novel environment and that males habituate faster than females. The current study's aim was to identify the neural substrates of separate effects of food and context novelty. Adult male and female rats were tested for consumption of a novel or familiar food in either a familiar or in a novel context. Test-induced Fos expression was measured in the amygdalar, thalamic, striatal, and prefrontal cortex regions that are important for appetitive responding, contextual processing, and reward motivation. Food and context novelty induced strikingly different activation patterns. Novel context induced Fos robustly in almost every region analyzed, including the central (CEA) and basolateral complex nuclei of the amygdala, the thalamic paraventricular (PVT) and reuniens nuclei, the nucleus accumbens (ACB), the medial prefrontal cortex prelimbic and infralimbic areas, and the dorsal agranular insular cortex (AI). Novel food induced Fos in a few select regions: the CEA, anterior basomedial nucleus of the amygdala, anterior PVT, and posterior AI. There were also sex differences in activation patterns. The capsular and lateral CEA had greater activation for male groups and the anterior PVT, ACB ventral core and shell had greater activation for female groups. These activation patterns and correlations between regions, suggest that distinct functional circuitries control feeding behavior when food is novel and when eating occurs in a novel environment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sustained visual attention allows us to process and react to unpredictable, behaviorally relevant sensory input. Sustained attention engages communication between the higher-order visual thalamus and its connected cortical regions. However, it remains unclear whether there is a causal relationship between oscillatory circuit dynamics and attentional behavior in these thalamo-cortical circuits. By using rhythmic optogenetic stimulation in the ferret, we provide causal evidence that higher-order visual thalamus coordinates thalamo-cortical and cortico-cortical functional connectivity during sustained attention via spike-field phase locking. Increasing theta but not alpha power in the thalamus improved accuracy and reduced omission rates in a sustained attention task. Further, the enhancement of effective connectivity by stimulation was correlated with improved behavioral performance. Our work demonstrates a potential circuit-level causal mechanism for how the higher-order visual thalamus modulates cortical communication through rhythmic synchronization during sustained attention., Competing Interests: Declaration of interests F.F. is the lead inventor of intellectual property filed on the topics of noninvasive brain stimulation by the University of North Carolina. F.F. serves as a paid consultant to Electromedical Products International. The work presented here is completely unrelated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness., (© 2024. The Author(s).)

Sleep spindles are major oscillatory components of Non-Rapid Eye Movement (NREM) sleep, reflecting hyperpolarization-rebound sequences of thalamocortical neurons. Reports suggest a link between sleep spindles and several forms of high-frequency oscillations which are considered as expressions of pathological off-line neural plasticity in the central nervous system. Here we investigated the relationship between thalamic sleep spindles and ripples in the anterior and mediodorsal nuclei (ANT and MD) of epilepsy patients. Whole-night LFP from the ANT and MD were co-registered with scalp EEG/polysomnography by using externalized leads in 15 epilepsy patients undergoing a Deep Brain Stimulation protocol. Slow (~12 Hz) and fast (~14 Hz) sleep spindles were present in the human ANT and MD and roughly, 20% of them were associated with ripples. Ripple-associated thalamic sleep spindles were characterized by longer duration and exceeded pure spindles in terms of spindle power as indicated by time-frequency analysis. Furthermore, ripple amplitude was modulated by the phase of sleep spindles within both thalamic nuclei. No signs of pathological processes were correlated with measures of ripple and spindle association, furthermore, the density of ripple-associated sleep spindles in the ANT showed a positive correlation with verbal comprehension. Our findings indicate the involvement of the human thalamus in coalescent spindle-ripple oscillations of NREM sleep., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Behavior relies on activity in structured neural circuits that are distributed across the brain, but most experiments probe neurons in a single area at a time. Using multiple Neuropixels probes, we recorded from multi-regional loops connected to the anterior lateral motor cortex (ALM), a circuit node mediating memory-guided directional licking. Neurons encoding sensory stimuli, choices, and actions were distributed across the brain. However, choice coding was concentrated in the ALM and subcortical areas receiving input from the ALM in an ALM-dependent manner. Diverse orofacial movements were encoded in the hindbrain; midbrain; and, to a lesser extent, forebrain. Choice signals were first detected in the ALM and the midbrain, followed by the thalamus and other brain areas. At movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The pulvinar nucleus of the thalamus is a crucial component of the visual system and plays significant roles in sensory processing and cognitive integration. The pulvinar's extensive connectivity with cortical regions allows for bidirectional communication, contributing to the integration of sensory information across the visual hierarchy. Recent findings underscore the pulvinar's involvement in attentional modulation, feature binding, and predictive coding. In this review, we highlight recent advances in clarifying the pulvinar's circuitry and function. We discuss the contributions of the pulvinar to signal modulation across the global cortical network and place these findings within theoretical frameworks of cortical processing, particularly the global neuronal workspace (GNW) theory and predictive coding., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)