Thalamic Level Research Articles

Altered brain perfusion and oxygen levels relate to sleepiness and attention in post-COVID syndrome.

Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS). Using resting-state functional magnetic resonance imaging, we investigated brain perfusion and oxygen level estimates in 47 patients (44.4 ± 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants. Group differences were calculated using two-sample t-tests. Multivariable linear regression was used for associations of each regional perfusion and oxygen level measure with cognition and sleepiness measures. Exploratory hazard ratios were calculated for each brain metric with clinical measures. Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%). We found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-FDR) = 0.038) and cortical grey matter (p-FDR = 0.015). Brain perfusion did not differ between patients and healthy participants. However, delayed patient caudate nucleus perfusion was associated with better executive function (p-FDR = 0.008). Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034). Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019). Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017). Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function. These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.

Reduced Thalamic γ-Aminobutyric Acid (GABA) in Painless but Not Painful Diabetic Peripheral Neuropathy.

Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with Painless- and Painful-diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including GABA (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a Magnetic Resonance Spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterised cohort of participants with Painless- and Painful-DPN. Participants with DPN (Painful- and Painless combined) had a significantly lower GABA:H2O ratio compared to those without DPN (Healthy volunteers [HV] and diabetes without DPN [No-DPN]). Participants with Painless-DPN had the lowest GABA:H2O ratio, which reached significance compared with HV and No-DPN, but not Painful-DPN. There was no difference in GABA:H2O in Painful-DPN compared with all other groups. A significant correlation with GABA:H2O and neuropathy severity was also seen. This study demonstrates that lower levels of thalamic GABA in participants with Painless-DPN may reflect neuroplasticity due to reduced afferent pain impulses. Whereas partially preserved levels of GABA in Painful-DPN may indicate that central GABAergic pathways are involved in the mechanisms of neuropathic pain in diabetes.

Vulnerability of Thalamic Nuclei at CSF Interface During the Entire Course of Multiple Sclerosis.

Thalamic atrophy can be used as a proxy for neurodegeneration in multiple sclerosis (MS). Some data point toward thalamic nuclei that could be affected more than others. However, the dynamic of their changes during MS evolution and the mechanisms driving their differential alterations are still uncertain. We paired a large cohort of 1,123 patients with MS with the same number of healthy controls, all scanned with conventional 3D-T1 MRI. To highlight the main atrophic regions at the thalamic nuclei level, we validated a segmentation strategy consisting of deep learning-based synthesis of sequences, which were used for automatic multiatlas segmentation. Then, through a lifespan-based approach, we could model the dynamics of the 4 main thalamic nuclei groups. All analyses converged toward a higher rate of atrophy for the posterior and medial groups compared with the anterior and lateral groups. We also demonstrated that focal MS white matter lesions were associated with atrophy of groups of nuclei when specifically located within the associated thalamocortical projections. The volumes of the most affected posterior group, but also of the anterior group, were better associated with clinical disability than the volume of the whole thalamus. These findings point toward the thalamic nuclei adjacent to the third ventricle as more susceptible to neurodegeneration during the entire course of MS through potentiation of disconnection effects by regional factors. Because this information can be obtained even from standard T1-weighted MRI, this paves the way toward such an approach for future monitoring of patients with MS.

Reduced sleep quality defines a subtype of obsessive-compulsive disorder with lower Glx levels in the resting thalamus and worse response inhibition

BackgroundThe aim of this study was to investigate the differences between resting and active thalamic neurometabolite levels and inhibitory function in obsessive compulsive disorder (OCD) patients with poor sleep quality (PSQ was defined as Pittsburgh Sleep Quality Index >5 and sleep efficiency ≤85%) compared to OCD patients with good sleep quality (GSQ) and healthy controls (HCs), as well as the relationship of these indices to obsessive compulsive symptoms. MethodsFunctional magnetic resonance spectroscopy (fMRS) was used to measure resting and active thalamic neurometabolite levels in 72 subjects (20 HCs and 38 OCD patients included in study analysis). Response inhibition function was measured by the Go-Nogo task before and during MRS recording. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The symptoms of OCD, anxiety and depression were evaluated using relevant clinical scales. ResultsOCD patients exhibited significantly reduced Glx/Cr levels in the resting thalamus. The levels of resting thalamic Glu/Cr and Glx/Cr in OCD patients with PSQ were significantly lowest. OCD patients had significantly lower correct rates on Go tasks, higher error rates on Nogo tasks, and longer error average response times (EART) to the Nogo task. OCD patients with PSQ demonstrated the highest Nogo task error rate and the longest EART to Nogo task. Furthermore, PSQI scores exhibited negative correlations with Glu/Cr and Glx/Cr in the resting thalamus. ConclusionOCD patients with PSQ demonstrated reduced levels of thalamic resting Glx and more pronounced response inhibitory function impairment. Aberrant neurometabolite levels in critical brain regions, coupled with heightened response inhibition function deficits, may be a neurobiological basis for the PSQ that OCD patients generally exhibit.

Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI.

Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Tocotrienol supplementations ameliorate oxidative stress in thalamus of rats exposed to low-to-moderate doses of ethanol

Background: Functional deterioration of thalamic structures has been reported in many occasions of ethanol-induced neurodegeneration. Neuroprotective role of Tocotrienol (T3) is well established along with its antioxidant property. Interaction of oral T3 supplementation modalities with the thalamic oxidative stress parameters were studied in low-to-moderate doses of ethanol (Et) exposures. Materials and Methods: Four phase of experiments were carried out with nil (Et-0) and three doses of Et exposures (Et-I, Et-II and Et-III) for 4 weeks. In each phase, 4 groups of Wistar rats were maintained with sham supplementation (NT3), prior supplementation (PT3), simultaneous supplementation (ST3) and total supplementation (TT3) with T3 for 6 weeks. Thalamic levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were estimated. Results: Two-way ANOVA demonstrated that all the thalamic GSH and LPO were significantly influenced by the modalities of T3 supplementation. However, low-to-moderate doses of Et exposures contributed significantly in alterations of only LPO level of thalamus. Conclusion: Out of the tested modalities, best protection in terms of oxidative stress was observed when prior and simultaneous supplementation modalities were combined (TT3).

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington’s Disease

BackgroundHuntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored.MethodsWe used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models.ResultsHere, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes.ConclusionsIn conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.

Deep Learning-Based Versus Iterative Image Reconstruction for Unenhanced Brain CT: A Quantitative Comparison of Image Quality.

This exploratory retrospective study aims to quantitatively compare the image quality of unenhanced brain computed tomography (CT) reconstructed with an iterative (AIDR-3D) and a deep learning-based (AiCE) reconstruction algorithm. After a preliminary phantom study, AIDR-3D and AiCE reconstructions (0.5 mm thickness) of 100 consecutive brain CTs acquired in the emergency setting on the same 320-detector row CT scanner were retrospectively analyzed, calculating image noise reduction attributable to the AiCE algorithm, artifact indexes in the posterior cranial fossa, and contrast-to-noise ratios (CNRs) at the cortical and thalamic levels. In the phantom study, the spatial resolution of the two datasets proved to be comparable; conversely, AIDR-3D reconstructions showed a broader noise pattern. In the human study, median image noise was lower with AiCE compared to AIDR-3D (4.7 vs. 5.3, p < 0.001, median 19.6% noise reduction), whereas AIDR-3D yielded a lower artifact index than AiCE (7.5 vs. 8.4, p < 0.001). AiCE also showed higher median CNRs at the cortical (2.5 vs. 1.8, p < 0.001) and thalamic levels (2.8 vs. 1.7, p < 0.001). These results highlight how image quality improvements granted by deep learning-based (AiCE) and iterative (AIDR-3D) image reconstruction algorithms vary according to different brain areas.

The Known Biology of Neuropathic Pain and Its Relevance to Pain Management.

Patients with neuropathic pain are heterogeneous in pathophysiology, etiology, and clinical presentation. Signs and symptoms are determined by the nature of the injury and factors such as genetics, sex, prior injury, age, culture, and environment. Basic science has provided general information about pain etiology by studying the consequences of peripheral injury in rodent models. This is associated with the release of inflammatory cytokines, chemokines, and growth factors that sensitize sensory nerve endings, alter gene expression, promote post-translational modification of proteins, and alter ion channel function. This leads to spontaneous activity in primary afferent neurons that is crucial for the onset and persistence of pain and the release of secondary mediators such as colony-stimulating factor 1 from primary afferent terminals. These promote the release of tertiary mediators such as brain-derived neurotrophic factor and interleukin-1β from microglia and astrocytes. Tertiary mediators facilitate the transmission of nociceptive information at the spinal, thalamic, and cortical levels. For the most part, these findings have failed to identify new therapeutic approaches. More recent basic science has better mirrored the clinical situation by addressing the pathophysiology associated with specific types of injury, refinement of methodology, and attention to various contributory factors such as sex. Improved quantification of sensory profiles in each patient and their distribution into defined clusters may improve translation between basic science and clinical practice. If such quantification can be traced back to cellular and molecular aspects of pathophysiology, this may lead to personalized medicine approaches that dictate a rational therapeutic approach for each individual.

Study of high-altitude cerebral edema using multimodal imaging.

To analyze the brain imaging features of high-altitude cerebral edema (HACE) using computed tomography (CT) and multi-sequence magnetic resonance imaging (MRI) and to explore its injury characteristics. We selected 30 patients with HACE diagnosed between January 2012 to August 2022 as the experimental group and 60 patients with dizziness on traveling from the plain to the plateau or from lower altitude to higher altitude in a short period of time as the control group. We collected general clinical data from the experimental group and classified it according to clinical symptoms. In both groups, we then performed a head CT and multi-sequence MRI (T1WI, T2WI, FLAIR, and DWI). Among them, nine patients with HACE were also scanned using susceptibility-weighted imaging (SWI). Finally, we analyzed the images. According to clinical symptoms, we divided the 30 cases of HACE into 12 mild cases and 18 severe cases. There was no significant difference in sex, age, leukocyte, neutrophil, or glucose content between mild and severe HACE. The sensitivity and specificity of the MRI diagnosis were 100 and 100%, respectively, while the sensitivity and specificity of the CT diagnosis were 23.3 and 100%, respectively. The distribution range of deep and juxtacortical white matter edema was significantly larger in severe HACE than in mild HACE (p < 0.001). The corpus callosum edema distribution range in severe HACE was significantly larger than that in mild HACE (p = 0.001). The ADC value of the splenium of the corpus callosum was significantly lower in severe HACE than in mild HACE (p = 0.049). In mild and severe HACE, the signal intensity of the DWI sequence was significantly higher than that of conventional MRI sequences (T1WI, T2WI, FLAIR) (p = 0.008, p = 0.025, respectively). In severe HACE, seven cases showed bilateral corticospinal tract edema at the thalamic level, and SWI showed cerebral microbleeds (CMBs) in five cases, especially in the corpus callosum. MRI has more advantages than CT in the evaluation of HACE, especially in the DWI sequence. The white matter injury of severe HACE is more severe and extensive, especially in the corpus callosum, and some CMBs and corticospinal tract edema may also appear.

Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex

Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks.

Ventral posteromedial nucleus of the thalamus as a neuroanatomical target for the anticephalalgic action of valproic acid and metamizole

Introduction. Valproic acid and metamizole are widely used in the treatment of primary headaches. However, despite the drugs’ proven clinical efficacy, the neurophysiological mechanisms underlying their therapeutic action are poorly understood. The ventral posteromedial nucleus of the thalamus (VPM) serves as the highest suprasegmental relay center for transmitting ascending nociceptive information from the cranial structures to the cerebral cortex and is considered as a potential neuroanatomical target for anticephalalgic drugs.The objective of the study was to evaluate the action of valproate and metamizole on the excitability of the VPM thalamic neurons.Methods and materials. In acute controlled experiments on anesthetized rats (n=31), we studied the action of cumulative dosing (three fixed dose injections every 30 minutes) of intravenously administered valproate (n=8, 100 mg/kg x 3) or metamizole (n=16,150 mg/kg · 3) on extracellularly recorded background and dura mater electrical stimulation-evoked activities of the convergent VPM neurons. Results. In all experiments, intravenous valproate significantly inhibited both background activity of the VPM neurons and their responses to dural electrostimulation. Metamizole had a similar action in more than half of the cases, whereas 44 % of the examined thalamic cells (7 out of 16) did not react to its infusion.Conclusion. One of the main neurophysiological mechanisms underlying anticephalalgic action of valproic acid and metamizole may be inhibition of the nociceptive transmission at the thalamic level due to the drugs-induced suppression of the meningeal-sensitive VPM neurons excitability.

Add-On MEmaNtine to Dopamine Antagonism to Improve Negative Symptoms at First Psychosis- the AMEND Trial Protocol.

BackgroundAntipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis.AimsThis investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine.Materials and EquipmentAntipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment.Outcome MeasuresThe primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes.Anticipated ResultsWe hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning.PerspectivesBy combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04789915].

Thalamic Neurometabolite Alterations in Chronic Low Back Pain: A Common Phenomenon across Musculoskeletal Pain Conditions?

A previous study by our group showed that knee osteoarthritis (KOA) patients demonstrate alterations in the thalamic levels of several metabolites, as measured by 1H-magnetic resonance spectroscopy: i.e., higher myo-inositol (mIns), lower N-acetylaspartate (NAA) and lower Choline (Cho), when compared to healthy controls. We sought to replicate these results in a different musculoskeletal pain condition, chronic low back pain (cLBP), and explore whether these metabolites would resolve clinical subtypes of cLBP. Twenty-nine cLBP patients (twenty-two with axial low back pain, cLBPAX, and seven with radicular low back pain, cLBPRAD), and twenty healthy controls were scanned using a conventional PRESS sequence (TE=30ms; TR=1.7s; voxel size=15 × 15 × 15mm) with voxel placement in the left thalamus. Using water-normalized levels, cLBP patients demonstrated higher mIns (p<0.01), lower NAA (p<0.001) and lower Cho (p<0.05) than healthy controls, replicating our prior KOA results in this cLBP cohort. Additionally, NAA was reduced in cLBPAX when compared to cLBPRAD (p<0.05), whereas differences found in Cho and mIns were not statistically significant (p<0.20 and p<0.15, respectively). While pain severity scores were not correlated with metabolite levels, the degree of nociplastic pain, as measured by score on the American College of Rheumatology Fibromyalgia Survey, negatively correlated with NAA. These results suggest that thalamic metabolite changes may be common across spatially different musculoskeletal chronic pain conditions for mIns, a marker of glial dysfunction, NAA, a marker of neuronal integrity, and Cho, a membrane turnover marker. Additionally, the differences between cLBP subtypes suggest that neuronal integrity may have a role to play in the pathophysiology of nociplastic pain. Grant support from 1-R01-NS094306-01A1 (MLL); 1-R01-NS09593701A1 (MLL).

FV 1 Segregating the prefrontal cortex by means of deep brain stimulation

Introduction: Neurocircuits are involved in the motor, cognitive, and affective dysfunctions of multiple brain disorders. Functional segregation into these domains has been widely defined on a fronto- cortical basis. However, despite considerable interaction, these functional domains remain partitioned to some extent at (sub)thalamic levels (1). To map the functional organization of the the frontal cortex (FC), we employ optimal connectivity profiles from successful deep brain stimulation (DBS) electrodes to the same target, which receives input from the entire FC, in four different disorders. Specifically, we identify cortical projection sites that, on a group level, associate with maximal improvements following subthalamic nucleus (STN) DBS in dystonia (DYT), Parkinson's disease (PD), Tourette syndrome (TS) or obsessive-compulsive disorder (OCD). Patients and Methods: Using Lead-DBS (2), stimulation volumes were estimated for six patient cohorts from six centers, each implanted with DBS to the STN for treatment of either DYT (N = 62), PD (N = 51), TS (N = 14), or OCD (N = 19). Via DBS Network Mapping (3) we derived disease-specific structural connections between cortex and STN from a normative connectome (4) that relate to optimal clinical outcomes. Results: Functional organization in the STN and FC was reflected along a caudo-rostral gradient (Fig. 1). Beneficial DBS networks for DYT predominantly projected to the primary motor cortex, while in PD, electrode connectivity to pre- and supplementary motor areas, in TS to the dorsomedial preFC, and in OCD to ventromedial, dorsal anterior cingulate and dorsolateral preFC emerged. Conclusion: Our findings demonstrate the usefulness of DBS to investigate the organizational gradient of frontal network (dys)function. As such, they bear both interest for cognitive neurosciences as well as clinical-translational value for circuit-guided DBS.

Striatal Injury Induces Overall Brain Alteration at the Pallial, Thalamic, and Cerebellar Levels.

Simple SummaryMagnetic resonance imaging showed that striatal injury leads to structural changes within several brain areas. Here, we specify these changes via gene expression of synaptic plasticity markers, neuronal markers, assessing the number of newborn cells as well as cell densities. We found that the injury resulted in long-lasting modifications involving plasticity and neural protection mechanisms in areas directly as well as indirectly connected with the damaged striatum, including the cerebellum.The striatal region Area X plays an important role during song learning, sequencing, and variability in songbirds. A previous study revealed that neurotoxic damage within Area X results in micro and macrostructural changes across the entire brain, including the downstream dorsal thalamus and both the upstream pallial nucleus HVC (proper name) and the deep cerebellar nuclei (DCN). Here, we specify these changes on cellular and gene expression levels. We found decreased cell density in the thalamic and cerebellar areas and HVC, but it was not related to neuronal loss. On the contrary, perineuronal nets (PNNs) in HVC increased for up to 2 months post-lesion, suggesting their protecting role. The synaptic plasticity marker Forkhead box protein P2 (FoxP2) showed a bi-phasic increase at 8 days and 3 months post-lesion, indicating a massive synaptic rebuilding. The later increase in HVC was associated with the increased number of new neurons. These data suggest that the damage in the striatal vocal nucleus induces cellular and gene expression alterations in both the efferent and afferent destinations. These changes may be long-lasting and involve plasticity and neural protection mechanisms in the areas directly connected to the injury site and also to distant areas, such as the cerebellum.

MAFLD progression contributes to altered thalamus metabolism and brain structure

Metabolic associated fatty liver disease (MAFLD), commonly known as non-alcoholic fatty liver disease, represents a continuum of events characterized by excessive hepatic fat accumulation which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and in some severe cases hepatocellular carcinoma. MAFLD might be considered as a multisystem disease that affects not only the liver but involves wider implications, relating to several organs and systems, the brain included. The present study aims to investigate changes associated with MAFLD-induced alteration of thalamic metabolism in vivo. DIAMOND (Diet-induced animal model of non-alcoholic fatty liver disease) mice were fed a chow diet and tap water (NC NW) or fat Western Diet (WD SW) for up to 28 weeks. At the baseline and weeks 4, 8, 20, 28 the thalamic neurochemical profile and total cerebral brain volume were evaluated longitudinally in both diet groups using 1H-MRS. To confirm the disease progression, at each time point, a subgroup of animals was sacrificed, the livers excised and placed in formalin. Liver histology was assessed and reviewed by an expert liver pathologist. MAFLD development significantly increases the thalamic levels of total N-acetylaspartate, total creatine, total choline, and taurine. Furthermore, in the WD SW group a reduction in total cerebral brain volume has been observed (p < 0.05 vs NC NW). Our results suggest that thalamic energy metabolism is affected by MAFLD progression. This metabolic imbalance, that is quantifiable by 1H-MRS in vivo, might cause structural damage to brain cells and dysfunctions of neurotransmitter release.

Neural processing: Cracking the code to extract relevant social information

How does the brain decode sensory features from social signals? A new study in electric fish provides an elegant model where mixed selectivity coding and corollary discharges at the thalamic level can guide decision making in social behavior.

TUALANG HONEY MODULATED NOCICEPTIVE RESPONSES IN THE THALAMUS OF REM SLEEP DEPRIVATION RAT MODEL

Sleep deprivation has been shown to alter pain responses in humans and animals. The present study investigated whether the administration of Tualang honey in the rapid eye movement (REM) sleep deprivation rat model would modulate nociceptive responses with associated changes in the thalamus. Forty-eight Sprague Dawley male rats were randomised into four groups (n=12 for each group): control group (FMC), REM sleep deprivation (REMsd), REM sleep deprivation pretreated with Tualang Honey for 1 month (REMsdH) and tank control (TC). Following sleep deprivation for 72 hours, a formalin test was conducted and pain behaviour was recorded and analysed. The rats were sacrificed, and the brains were removed for histological examination and assessment of N-methyl-D-aspartate receptor (NMDA R2) level in the thalamus. REMsdH group showed a significantly lower level of pain behaviour score and NMDA R2 compared to the REMsd group (p&lt;0.05). In addition, REMsdH also demonstrated a significantly higher number of Nissl stained neurons in comparison with the REMsd group (p&lt;0.05). Furthermore, dark neurons, suggestive of neuronal damage, were observed in the REMsd group. In conclusion, administration of Tualang honey before REM sleep deprivation modulated nociceptive responses and prevent changes in thalamic neurons and NMDA R2 level.

Reward disturbances in antipsychotic-naïve patients with first-episode psychosis and their association to glutamate levels.

Aberrant anticipation of motivational salient events and processing of outcome evaluation in striatal and prefrontal regions have been suggested to underlie psychosis. Altered glutamate levels have likewise been linked to schizophrenia. Glutamatergic abnormalities may affect the processing of motivational salience and outcome evaluation. It remains unresolved, whether glutamatergic dysfunction is associated with the coding of motivational salience and outcome evaluation in antipsychotic-naïve patients with first-episode psychosis. Fifty-one antipsychotic-naïve patients with first-episode psychosis (22 ± 5.2 years, female/male: 31/20) and 52 healthy controls (HC) matched on age, sex, and parental education underwent functional magnetic resonance imaging and magnetic resonance spectroscopy (3T) in one session. Brain responses to motivational salience and negative outcome evaluation (NOE) were examined using a monetary incentive delay task. Glutamate levels were estimated in the left thalamus and anterior cingulate cortex using LCModel. Patients displayed a positive signal change to NOE in the caudate (p = 0.001) and dorsolateral prefrontal cortex (DLPFC; p = 0.003) compared to HC. No group difference was observed in motivational salience or in levels of glutamate. There was a different association between NOE signal in the caudate and DLPFC and thalamic glutamate levels in patients and HC due to a negative correlation in patients (caudate: p = 0.004, DLPFC: p = 0.005) that was not seen in HC. Our findings confirm prior findings of abnormal outcome evaluation as a part of the pathophysiology of schizophrenia. The results also suggest a possible link between thalamic glutamate and NOE signaling in patients with first-episode psychosis.