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Brain Stimulation 2024
Letter of response to "concerns about efficacy of deep brain stimulation (DBS) in centromedian-parafascicular thalamic complex for rapid onset dystonia-parkinsonism (DYT12-ATP1A3)".
Topics: Deep Brain Stimulation; Humans; Dystonic Disorders; Parkinsonian Disorders; Intralaminar Thalamic Nuclei
PubMed: 38685262
DOI: 10.1016/j.brs.2024.02.015 -
Brain Stimulation 2024
Topics: Deep Brain Stimulation; Humans; Dystonic Disorders; Intralaminar Thalamic Nuclei; Parkinsonian Disorders; Sodium-Potassium-Exchanging ATPase
PubMed: 38685261
DOI: 10.1016/j.brs.2024.02.008 -
Cell Reports May 2024The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the...
The sensory cortex receives synaptic inputs from both first-order and higher-order thalamic nuclei. First-order inputs relay simple stimulus properties from the periphery, whereas higher-order inputs relay more complex response properties, provide contextual feedback, and modulate plasticity. Here, we reveal that a cortical neuron's higher-order input is determined by the type of progenitor from which it is derived during embryonic development. Within layer 4 (L4) of the mouse primary somatosensory cortex, neurons derived from intermediate progenitors receive stronger higher-order thalamic input and exhibit greater higher-order sensory responses. These effects result from differences in dendritic morphology and levels of the transcription factor Lhx2, which are specified by the L4 neuron's progenitor type. When this mechanism is disrupted, cortical circuits exhibit altered higher-order responses and sensory-evoked plasticity. Therefore, by following distinct trajectories, progenitor types generate diversity in thalamocortical circuitry and may provide a general mechanism for differentially routing information through the cortex.
Topics: Animals; Mice; Thalamus; Transcription Factors; Somatosensory Cortex; LIM-Homeodomain Proteins; Neurons; Neuronal Plasticity; Mice, Inbred C57BL
PubMed: 38678557
DOI: 10.1016/j.celrep.2024.114157 -
International Journal of Molecular... Apr 2024Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months....
Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.
Topics: Animals; Ketamine; Microglia; Rats, Sprague-Dawley; Rats; Male; Synapses; Head Injuries, Closed; Axons; Disease Models, Animal; Geniculate Bodies; Brain Concussion; Disks Large Homolog 4 Protein; Synapsins; Neuroprotective Agents
PubMed: 38673871
DOI: 10.3390/ijms25084287 -
Brain Sciences Apr 2024The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human... (Review)
Review
The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human primates. However, studies aiming to harmonize the definition of the cortical layers and borders of V1 across rodents and primates are very limited. This article attempts to identify and harmonize the molecular markers and connectional patterns that can consistently link corresponding cortical layers of V1 and borders across mammalian species and ages. V1 in primates has at least two additional and unique layers (L3b2 and L3c) and two sublayers of layer 4 (L4a and L4b) compared to rodent V1. In all species examined, layers 4 and 3b of V1 receive strong inputs from the (dorsal) lateral geniculate nucleus, and V1 is mostly surrounded by the secondary visual cortex except for one location where V1 directly abuts area prostriata. The borders of primate V1 can also be clearly identified at mid-gestational ages using gene markers. In rodents, a novel posteromedial extension of V1 is identified, which expresses V1 marker genes and receives strong inputs from the lateral geniculate nucleus. This V1 extension was labeled as the posterior retrosplenial cortex and medial secondary visual cortex in the literature and brain atlases. Layer 6 of the rodent and primate V1 originates corticothalamic projections to the lateral geniculate, lateral dorsal, and reticular thalamic nuclei and the lateroposterior-pulvinar complex with topographic organization. Finally, the direct geniculo-extrastriate (particularly the strong geniculo-prostriata) projections are probably major contributors to blindsight after V1 lesions. Taken together, compared to rodents, primates, and humans, V1 has at least two unique middle layers, while other layers are comparable across species and display conserved molecular markers and similar connections with the visual thalamus with only subtle differences.
PubMed: 38672021
DOI: 10.3390/brainsci14040372 -
Somatotopy of the sensory thalamus: inputs from directional deep brain stimulation in pain patients.Annals of Clinical and Translational... Apr 2024The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using...
OBJECTIVE
The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using directional VP deep brain stimulation (DBS) in patients treated for chronic neuropathic pain.
METHODS
Six patients with central (four) or peripheral (two) neuropathic pain were treated by VP DBS using directional leads in a prospective study (clinicaltrials.gov NCT03399942). Lead-DBS toolbox was used for leads localization, visualization, and modeling of the volume of tissue activated (VTA). Stimulation was delivered in each direction, 1 month after surgery and correlated to the location of stimulation-induced paresthesias. The somatotopy was modeled by correlating the respective locations of paresthesias and VTAs. We recorded 48 distinct paresthesia maps corresponding to 48 VTAs (including 36 related to directional stimulation).
RESULTS
We observed that, in each patient, respective body representations of the trunk, upper limb, lower limb, and head were closely located around the lead. These representations differed across patients, did not follow a common organization and were not concordant with the previously described somatotopic organization of the sensory thalamus.
INTERPRETATION
Thalamic reorganization has been reported in chronic pain patients compared to non-pain patients operated for movement disorders in previous studies using intraoperative recordings and micro-stimulation. Using a different methodology, namely 3D representation of the VTA by the directional postoperative stimulation through a stationary electrode, our study brings additional arguments in favor of a reorganization of the VP thalamic somatotopy in patients suffering from chronic neuropathic pain of central or peripheral origin.
PubMed: 38668642
DOI: 10.1002/acn3.52067 -
Nature Communications Apr 2024The 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...
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.
Topics: Animals; Wakefulness; Somatosensory Cortex; Mice; Thalamus; Optogenetics; Vibrissae; Neurons; Male; Neural Pathways; Ventral Thalamic Nuclei; Action Potentials; Female; Mice, Inbred C57BL
PubMed: 38664415
DOI: 10.1038/s41467-024-47863-8 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2024The high-order cognitive and executive functions are necessary for an individual to survive. The densely bidirectional innervations between the medial prefrontal cortex...
The high-order cognitive and executive functions are necessary for an individual to survive. The densely bidirectional innervations between the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) play a vital role in regulating high-order functions. Pyramidal neurons in mPFC have been classified into several subclasses according to their morphological and electrophysiological properties, but the properties of the input-specific pyramidal neurons in mPFC remain poorly understood. The present study aimed to profile the morphological and electrophysiological properties of mPFC pyramidal neurons innervated by MD. In the past, the studies for characterizing the morphological and electrophysiological properties of neurons mainly relied on the electrophysiological recording of a large number of neurons and their morphologic reconstructions. But, it is a low efficient method for characterizing the circuit-specific neurons. The present study combined the advantages of traditional morphological and electrophysiological methods with machine learning to address the shortcomings of the past method, to establish a classification model for the morphological and electrophysiological properties of mPFC pyramidal neurons, and to achieve more accurate and efficient identification of the properties from a small size sample of neurons. We labeled MD-innervated pyramidal neurons of mPFC using the trans-synaptic neural circuitry tracing method and obtained their morphological properties using whole-cell patch-clamp recording and morphologic reconstructions. The results showed that the classification model established in the present study could predict the electrophysiological properties of MD-innervated pyramidal neurons based on their morphology. MD-innervated pyramidal neurons exhibit larger basal dendritic length but lower apical dendrite complexity compared to non-MD-innervated neurons in the mPFC. The morphological characteristics of the two subtypes (ET-1 and ET-2) of mPFC pyramidal neurons innervated by MD are different, with the apical dendrites of ET-1 neurons being longer and more complex than those of ET-2 neurons. These results suggest that the electrophysiological properties of MD- innervated pyramidal neurons within mPFC correlate with their morphological properties, indicating that the different roles of these two subclasses in local circuits within PFC, as well as in PFC-cortical/subcortical brain region circuits.
Topics: Pyramidal Cells; Prefrontal Cortex; Animals; Rats; Mediodorsal Thalamic Nucleus; Male; Electrophysiological Phenomena; Neural Pathways; Machine Learning; Rats, Sprague-Dawley; Patch-Clamp Techniques
PubMed: 38658373
DOI: No ID Found -
Frontiers in Network Physiology 2024Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson's disease (PD)...
Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson's disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists' expertise and patients' experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients' symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity. In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim-DBS are linked to symptomatic changes in EMG signals. By using a proportional-integral-derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim-DBS so that the power of EMG reaches a desired control target. We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.
PubMed: 38650608
DOI: 10.3389/fnetp.2024.1356653 -
Brain Communications 2024The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding...
The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.
PubMed: 38638150
DOI: 10.1093/braincomms/fcae117