Thalamocortical Circuits Research Articles

Characterization and closed-loop control of infrared thalamocortical stimulation produces spatially constrained single-unit responses.

Deep brain stimulation (DBS) is a powerful tool for the treatment of circuitopathy-related neurological and psychiatric diseases and disorders such as Parkinson's disease and obsessive-compulsive disorder, as well as a critical research tool for perturbing neural circuits and exploring neuroprostheses. Electrically mediated DBS, however, is limited by the spread of stimulus currents into tissue unrelated to disease course and treatment, potentially causing undesirable patient side effects. In this work, we utilize infrared neural stimulation (INS), an optical neuromodulation technique that uses near to midinfrared light to drive graded excitatory and inhibitory responses in nerves and neurons, to facilitate an optical and spatially constrained DBS paradigm. INS has been shown to provide spatially constrained responses in cortical neurons and, unlike other optical techniques, does not require genetic modification of the neural target. We show that INS produces graded, biophysically relevant single-unit responses with robust information transfer in rat thalamocortical circuits. Importantly, we show that cortical spread of activation from thalamic INS produces more spatially constrained response profiles than conventional electrical stimulation. Owing to observed spatial precision of INS, we used deep reinforcement learning (RL) for closed-loop control of thalamocortical circuits, creating real-time representations of stimulus-response dynamics while driving cortical neurons to precise firing patterns. Our data suggest that INS can serve as a targeted and dynamic stimulation paradigm for both open and closed-loop DBS.

Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review.

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical-cortical interactions in arousal, few have explored the relationship between subcortical-cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression.

Spike-spindle coupling during sleep and its mechanism explanation in childhood focal epilepsy.

Childhood focal epilepsy (CFE) is a serious neurological disorder characterized by epileptic seizures arising from a focal or multi-focal zone of the brain in clinics. During non-rapid eye movement (NREM) sleep stage, epileptiform discharges become frequent, and sleep spindles are generated through local interaction between thalamic neurons for CFE patients. Recent research has shown that epileptiform spikes significantly induce spindle oscillations within 1s (say, spike-spindle coupling) during NREM sleep in focal epilepsy, which might damage cognitive function of epilepsy patients. However, the temporal interaction mechanism between spikes and spindles is lack of understanding. In this paper, we first develop a new thalamocortical model of CFE (CFE-TCM) by integrating M-type potassium current, persistent sodium current and NMDAR current into Costa model, where the three types of currents are important for modulating the excitability of thalamocortical system. Then we demonstrate in simulations that: (1) the temporal spike-spindle coupling oscillatory patterns do exist in real CFE-EEGs recorded in clinics; (2) the constructed model CFE-TCM has a capacity of generating spike-spindle coupling discharges, and the corresponding statistical results are consistent with those obtained from real EEGs; (3) the spike-spindle coupling discharges are mediated by the strength of long-range thalamus-cortex connections where the excitable projection from thalamocortical neuron in thalamus to pyramidal neuron in cortex takes a great role. The obtained results reveal that pathological spike-spindle coupling may be a potential marker of thalamocortical circuit dysfunction, which will provide a possible treatment strategy for disease progression and cognition impairment in focal epilepsy.

Blindness affects the developmental trajectory of the sleeping brain

Sleep plays a crucial role in brain development, sensory information processing, and consolidation. Sleep spindles are markers of these mechanisms as they mirror the activity of the thalamocortical circuits. Spindles can be subdivided into two groups, slow (10–13 Hz) and fast (13–16 Hz), which are each associated with different functions. Specifically, fast spindles oscillate in the high-sigma band and are associated with sensorimotor processing, which is affected by visual deprivation. However, how blindness influences spindle development has not yet been investigated. We recorded nap video-EEG of 50 blind/severely visually impaired (BSI) and 64 sighted children aged 5 months to 6 years old. We considered aspects of both macro- and micro-structural spindles. The BSI children lacked the evolution of developmental spindles within the central area. Specifically, young BSI children presented low central high-sigma and high-beta (25–30 Hz) event-related spectral perturbation and showed no signs of maturational decrease. High-sigma and high-beta activity in the BSI group correlated with clinical indices predicting perceptual and motor disorders. Our findings suggest that fast spindles are pivotal biomarkers for identifying an early developmental deviation in BSI children. These findings are critical for initial therapeutic intervention.

Sleep Spindle Alterations in Children With Migraine

BackgroundThe modulation of thalamocortical activity is the most important site of several levels of interference between sleep spindles and migraine. Thalamocortical circuits are responsible for the electrophysiological phenomenon of sleep spindles. Spindle alterations may be used as a beneficial marker in the diagnosis and follow-up of children with migraine. We aimed to formulate the hypothesis that there is a shared mechanism that underlies migraine and sleep spindle activity. MethodsWe analyzed the amplitude, frequency, duration, density, and activity of sleep spindles in non-rapid eye movement stage 2 sleep in patients with migraine without aura when compared with healthy control subjects. ResultsThe amplitudes of average, slow, and fast sleep spindles were higher in children with migraine without aura (P = 0.020, 0.013, and 0.033, respectively). The frequency of fast spindles was lower in children with migraines without aura when compared with the control group (P = 0.03). Although not statistically significant, the fast sleep spindle duration in the migraine group was shorter (P = 0.055). Multivariate analysis revealed an increased risk of migraine associated with increased mean spindle amplitude and decreased fast spindle frequency and duration. ConclusionsOur data suggest that spindle alterations may correlate with the vulnerability to develop migraine and may be used as a model for future research about the association between the thalamocortical networks and migraine.

Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model.

Impaired extinction of fear memory is one of the most common symptoms in post-traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD-ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle-based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD-related impaired extinction of fear memory and provide therapeutic insights into Kv3.2-targeted RNA therapy for PTSD.

Basic Science and Pathogenesis - Part 2.

Traumatic Brain Injury (TBI) is a known risk factor for developing a neurodegenerative disease later in life, including Alzheimer's Disease (AD) and other forms of tauopathy such as chronic traumatic encephalopathy (CTE) and frontal-temporal dementia (FTD). Although several studies highlight the relationship between the severity and frequency of a TBI and the development of these tauopathies, the mechanism behind this association remains unknown. Proper meningeal lymphatic function is required for clearance of waste products and protein aggregates such as amyloid beta and tau from the brain parenchyma. While post-TBI inflammation is beneficial for clearing debris and promoting tissue repair, prolonged glial activation and decreased meningeal lymphatic drainage have been linked to worsened cognitive function. A mild TBI (mTBI) was delivered to three-month-old young adult mice overexpressing P301S mutant human tau (PS19) through the skull on the right inferior temporal lobe of the brain. Sham and TBI injured mice were tested on behavioral tests at 5 months of age. At 7 months of age, brains were examined for tau pathology and neuroinflammation using confocal microscopy. Four months after mTBI, the brains of TBI PS19 mice exhibit increased levels of microglia and astrocytes, and increased P-S202/T-205-Tau in the cortex and thalamus of the ipsilateral hemisphere compared to the contralateral side and to Sham PS19 controls. These findings correlate with our behavior study showing increased hyperactivity, risk-taking behavior, and impaired short term working memory. PS19 TBI mice also present larger ventricles than their uninjured controls suggesting a potential loss of white matter in the cortex and/or hippocampus. P-S202/T-205-Tau orginated from the cortex near the injury site can aggregate and promote the formation of more toxic tau that spreads to deeper regions of the cortex and in the thalamus primarily through the thalamocortical circuit. Also, microglia and astrocyte activation and production of inflammatory mediators has been associated with synapse pruning and engulfment of damaged neurons expressing 'eat me signals' leading to neurodegeneration.

Functional ultrasound imaging of stroke in awake rats

Anesthesia is a major confounding factor in preclinical stroke research as stroke rarely occurs in sedated patients. Moreover, anesthesia affects both brain functions and the stroke outcome acting as neurotoxic or protective agents. So far, no approaches were well suited to induce stroke while imaging hemodynamics along with simultaneous large-scale recording of brain functions in awake animals. For this reason, the first critical hours following the stroke insult and associated functional alteration remain poorly understood. Here, we present a strategy to investigate both stroke hemodynamics and stroke-induced functional alterations without the confounding effect of anesthesia, i.e., under awake condition. Functional ultrasound (fUS) imaging was used to continuously monitor variations in cerebral blood volume (CBV) in +65 brain regions/hemispheres for up to 3 hr after stroke onset. The focal cortical ischemia was induced using a chemo-thrombotic agent suited for permanent middle cerebral artery occlusion in awake rats and followed by ipsi- and contralesional whiskers stimulation to investigate on the dynamic of the thalamocortical functions. Early (0–3 hr) and delayed (day 5) fUS recording enabled to characterize the features of the ischemia (location, CBV loss), spreading depolarizations (occurrence, amplitude) and functional alteration of the somatosensory thalamocortical circuits. Post-stroke thalamocortical functions were affected at both early and later time points (0–3 hr and 5 days) after stroke. Overall, our procedure facilitates early, continuous, and chronic assessments of hemodynamics and cerebral functions. When integrated with stroke studies or other pathological analyses, this approach seeks to enhance our comprehension of physiopathologies towards the development of pertinent therapeutic interventions.

Functional ultrasound imaging of stroke in awake rats.

Anesthesia is a major confounding factor in preclinical stroke research as stroke rarely occurs in sedated patients. Moreover, anesthesia affects both brain functions and the stroke outcome acting as neurotoxic or protective agents. So far, no approaches were well suited to induce stroke while imaging hemodynamics along with simultaneous large-scale recording of brain functions in awake animals. For this reason, the first critical hours following the stroke insult and associated functional alteration remain poorly understood. Here, we present a strategy to investigate both stroke hemodynamics and stroke-induced functional alterations without the confounding effect of anesthesia, i.e., under awake condition. Functional ultrasound (fUS) imaging was used to continuously monitor variations in cerebral blood volume (CBV) in +65 brain regions/hemispheres for up to 3 hr after stroke onset. The focal cortical ischemia was induced using a chemo-thrombotic agent suited for permanent middle cerebral artery occlusion in awake rats and followed by ipsi- and contralesional whiskers stimulation to investigate on the dynamic of the thalamocortical functions. Early (0-3 hr) and delayed (day 5) fUS recording enabled to characterize the features of the ischemia (location, CBV loss), spreading depolarizations (occurrence, amplitude) and functional alteration of the somatosensory thalamocortical circuits. Post-stroke thalamocortical functions were affected at both early and later time points (0-3 hr and 5 days) after stroke. Overall, our procedure facilitates early, continuous, and chronic assessments of hemodynamics and cerebral functions. When integrated with stroke studies or other pathological analyses, this approach seeks to enhance our comprehension of physiopathologies towards the development of pertinent therapeutic interventions.

A fixel-based analysis of white matter reductions early detects Parkinson disease with mild cognitive impairment

BackgroundWhite matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC). MethodsSeventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed. ResultsPatients with PD-MCI were significantly older (p = 0.044), had a higher male-to-female ratio (p = 0.006) and total Unified Parkinson's Disease Rating Scale score (p = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients. ConclusionsPD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

We developed a detailed model of macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator and NetPyNE tool. The A1 model simulates a cortical column with over 12,000 neurons and 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, and connectivity across six cortical layers. It is reciprocally connected to the MGB thalamus, which includes interneurons and core and matrix-layer-specific projections to A1. The model simulates multiscale measures, including physiological firing rates, local field potentials (LFPs), current source densities (CSDs), and electroencephalography (EEG) signals. Laminar CSD patterns, during spontaneous activity and in response to broadband noise stimulus trains, mirror experimental findings. Physiological oscillations emerge spontaneously across frequency bands comparable to those recorded invivo. We elucidate population-specific contributions to observed oscillation events and relate them to firing and presynaptic input patterns. The model offers a quantitative theoretical framework to integrate and interpret experimental data and predict its underlying cellular and circuit mechanisms.

Thalamo-cortical circuits associated with trait- and state-repetitive negative thinking in major depressive disorder

BackgroundRepetitive negative thinking (RNT), often referred to as rumination in the mood disorders literature, is a symptom dimension associated with poor prognosis and suicide in major depressive disorder (MDD). Given the transdiagnostic nature of RNT, this study aimed to evaluate the hypothesis that neurobiological substrates of RNT in MDD may share the brain mechanisms underlying obsessions, particularly those involving cortico-striatal-thalamic-cortical (CSTC) circuits. MethodsThirty-nine individuals with MDD underwent RNT induction during fMRI. Trait-RNT was measured by the Ruminative Response Scale (RRS) and state-RNT was measured by a visual analogue scale. We employed a connectome-wide association analysis examining the association between RNT intensity with striatal and thalamic connectivity. ResultsA greater RRS score was associated with hyperconnectivity of the right mediodorsal thalamus with prefrontal cortex, including lateral orbitofrontal cortex, along with Wernicke's area and posterior default mode network nodes (t = 4.66–6.70). A greater state-RNT score was associated with hyperconnectivity of the right laterodorsal thalamus with bilateral primary sensory and motor cortices, supplementary motor area, and Broca's area (t = 4.51–6.57). Unexpectedly, there were no significant findings related to the striatum. ConclusionsThe present results suggest RNT in MDD is subserved by abnormal connectivity between right thalamic nuclei and cortical regions involved in both visceral and higher order cognitive processing. Emerging deep-brain neuromodulation methods may be useful to establish causal relationships between dysfunction of right thalamic-cortical circuits and RNT in MDD.

Altered dynamic functional connectivity of the thalamus subregions in patients with schizophrenia

BackgroundPrevious neuroimaging studies indicated that patients with schizophrenia showed impaired thalamus and thalamo-cortical circuits. However, the dynamic functional connectivity (dFC) patterns of the thalamus remain unclear. In this study, we explored the dFC of the thalamus in SZ patients and whether clinical features are correlated with altered dFC. MethodsForty-three patients with schizophrenia and 31 healthy controls underwent 3.0 T rs-fMRI.Based on the human Brainnetome atlas, the thalamus is divided into 8 subregions. Subsequently, we performed flexible least squares method to calculate the dFC of each thalamus subregions. ResultsCompared with healthy controls, patients with schizophrenia exhibited increased dFC between the thalamus and cerebellar, visual-related cortex, sensorimotor-related cortex, and frontal lobe. In addition, we found that the dFC of the thalamus and the right fusiform gyrus was negatively associated with age of onset. ConclusionsOur findings demonstrated that the dFC of specific thalamus sub-regions is altered in patients with schizophrenia. Our results further suggested the dysconnectivity of thalamus plays an important role in the pathophysiology of schizophrenia.

Gating small conductance calcium-activated potassium channels in the thalamic reticular nucleus.

Small conductance calcium-activated potassium (SK) channels are well-known regulators of neuronal excitability. In the thalamic hub, SK2 channels act as pacemakers of thalamic reticular neurons, which play a key role in the thalamocortical circuit. Several disease-linked genes are highly enriched in these neurons, including genes known to be associated with schizophrenia and attentional disorders, which could affect neuronal firing. The present study assessed the effect of pharmacological modulation of SK channels in the firing pattern and intrinsic properties of thalamic reticular neurons by performing whole cell patch clamp recordings in brain slices. Two SK positive allosteric modulators and one negative allosteric modulator were used: CyPPA, NS309, and NS8593, respectively. By acting on the burst afterhyperpolarization (AHP), negative modulation of SK channels resulted in increased action potential (AP) firing, increased burst duration, and decreased intervals between bursts. Conversely, both CyPPA and NS309 increased the afterburst AHP, prolonging the interburst interval, which additionally resulted in reduced AP firing in the case of NS309. Alterations in SK channel activity would be expected to alter functioning of thalamocortical circuits. Targeting SK channels could be promising in treating disorders involving thalamic reticular dysfunction such as psychiatric and neurodevelopmental disorders.

Thermosensory thalamus: parallel processing across model organisms.

The thalamus acts as an interface between the periphery and the cortex, with nearly every sensory modality processing information in the thalamocortical circuit. Despite well-established thalamic nuclei for visual, auditory, and tactile modalities, the key thalamic nuclei responsible for innocuous thermosensation remains under debate. Thermosensory information is first transduced by thermoreceptors located in the skin and then processed in the spinal cord. Temperature information is then transmitted to the brain through multiple spinal projection pathways including the spinothalamic tract and the spinoparabrachial tract. While there are fundamental studies of thermal transduction via thermosensitive channels in primary sensory afferents, thermal representation in the spinal projection neurons, and encoding of temperature in the primary cortical targets, comparatively little is known about the intermediate stage of processing in the thalamus. Multiple thalamic nuclei have been implicated in thermal encoding, each with a corresponding cortical target, but without a consensus on the role of each pathway. Here, we review a combination of anatomy, physiology, and behavioral studies across multiple animal models to characterize the thalamic representation of temperature in two proposed thermosensory information streams.

Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations.

Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30-50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides an ex vivo method for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson's Disease patients.

Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined. We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery. Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization. Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.

Inhibitory Gating of Thalamocortical Inputs onto Rat Gustatory Insular Cortex.

In primary gustatory cortex (GC), a subregion of the insular cortex, neurons show anticipatory activity, encode taste identity and palatability, and their activity is related to decision-making. Inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc), dramatically reduces GC taste responses, consistent with the hypothesis that VPMpc-GC projections carry taste information. Recordings in awake rodents reported that taste-responsive neurons can be found across GC, without segregated spatial mapping, raising the possibility that projections from the taste thalamus may activate GC broadly. In addition, we have shown that cortical inhibition modulates the integration of thalamic and limbic inputs, revealing a potential role for GABA transmission in gating sensory information to GC. Despite this wealth of information at the system level, the synaptic organization of the VPMpc-GC circuit has not been investigated. Here, we used optogenetic activation of VPMpc afferents to GC in acute slice preparations from rats of both sexes to investigate the synaptic properties and organization of VPMpc afferents in GC and their modulation by cortical inhibition. We hypothesized that VPMpc-GC synapses are distributed across GC, but show laminar- and cell-specific properties, conferring computationally flexibility to how taste information is processed. We also found that VPMpc-GC synaptic responses are strongly modulated by the activity regimen of VPMpc afferents, as well as by cortical inhibition activating GABAA and GABAB receptors onto VPMpc terminals. These results provide a novel insight into the complex features of thalamocortical circuits for taste processing.SIGNIFICANCE STATEMENT We report that the input from the primary taste thalamus to the primary gustatory cortex (GC) shows distinct properties compared with primary thalamocortical synapses onto other sensory areas. Ventral posteromedial thalamic nucleus afferents in GC make synapses with excitatory neurons distributed across all cortical layers and display frequency-dependent short-term plasticity to repetitive stimulation; thus, they do not fit the classic distinction between drivers and modulators typical of other sensory thalamocortical circuits. Thalamocortical activation of GC is gated by cortical inhibition, providing local corticothalamic feedback via presynaptic ionotropic and metabotropic GABA receptors. The connectivity and inhibitory control of thalamocortical synapses in GC highlight unique features of the thalamocortical circuit for taste.

A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation.

For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.

Measurement of thalamus and cortical damages in hypoxic ischemic encephalopathy

BackgroundThe thalamic gray-white matter ratios (GWRs) on CT and quantitative suppression ratios (SRs) of background activities on EEG may reflect damages in the thalamus and cerebral hemispheres in patients with hypoxic-ischemic encephalopathy (HIE). MethodsThe inclusion criteria were (1) cardiac arrest patients over the age of 20 years from March 2010 to March 2020, and (2) patients who had both EEG and brain CT within 7 days after cardiac arrest. The thalamic GWRs were semi-quantitatively measured by using the region of interest (ROI). SRs of background were analyzed with the installed software (Persyst® v13) in EEG machine. Results175 patients were included among 686 patients with HIE and the thalamic GWRs of 168 patients were successfully measured. 155 patients (89 %) showed poor outcomes. The poor outcome group revealed not only higher SRs, but also lower thalamic GWRs. The thalamic GWRs showed a negative correlation to the SRs (ρ (rho) = −0.36, p < 0.0001 for right side, ρ (rho) = −0.31, p < 0.0001 for left side). The good outcome group showed neither beyond the cut-off values of thalamic GWRs nor SRs [40 % (59/148) VS 0 % (0/20) in right side, p = 0.0005 %, and 28 % (42/148) VS 0 % (0/20) in left side, p = 0.0061]. ConclusionThe thalamic GWRs and SRs may reflect the damage in the thalamus and cerebral hemispheres in patients with HIE. Insults in the thalamocortical circuit (TCC) or the thalamus might be responsible for the poor outcome.