Intrinsic disruption of white matter microarchitecture in major depressive disorder: A voxel-based meta analysis of diffusion tensor imaging.

BACKGROUND: Major depressive disorder (MDD) is a prevalent and disabling mood disorder, thought to be linked with brain white matter (WM) alterations. Prior diffusion tensor imaging (DTI) studies have reported inconsistent changes in fractional anisotropy (FA) across different brain regions in MDD patients. However, none of these studies utilized raw t-map data for WM meta-analysis in MDD. Our study aims to address this gap by conducting a whole-brain-based meta-analysis of FA in MDD using Seed-based d mapping via permutation of subject images (SDM-PSI), combining reported peak coordinates and raw statistical parametric maps. OBJECTIVES: Following PRISMA guidelines, we performed a systematic search and meta-analysis to compare FA in MDD patients with healthy controls (HC). Our goal was to identify WM abnormalities in MDD, using SDM, which could shed light on the disorder's pathogenesis. RESULTS: The meta-analysis included 39 studies with 3696 participants (2094 with MDD, 1602HC). It revealed that MDD patients, in comparison to HC, have lower FA in the corpus callosum (CC) and anterior thalamic projections (ATP). Subgroup analyses indicated that the CC is a more stable pathogenic factor in MDD. Meta-regression analyses showed no linear correlation between the mean age, percentage of female patients, duration of depression, and FA abnormalities. This suggests that WM impairments in interhemispheric connections and anterior thalamocortical circuits are significant in the pathogenesis of MDD.

Synaptic plasticity in human thalamocortical assembloids.

Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA sequencing revealed that >80% of cells in thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.

Microsurgical anatomy and approaches to thalamic gliomas. Part 1: A cartography guide for navigating to the thalamus. Integrating 3D model rendering with anatomical dissections.

OBJECTIVE: The selection of appropriate microsurgical approaches to treat thalamic pathologies is currently largely subjective. The objective of this study was to provide a structured cartography map for surgical navigation to treat gliomas involving different surfaces of the thalamus. METHODS: Fifteen formalin-fixed, silicone-injected cadavers (30 sides) were dissected, and 10 adult brain specimens (20 sides) were used to illustrate thalamic microsurgical anatomy using the Klingler fiber dissection technique. Exposures and trajectories for the six most common microsurgical approaches were depicted using MR data from healthy subjects converted into surface-rendered 3D virtual brain models. Additionally, thalamic surfaces exposed with all six approaches were color mapped on the virtual 3D model and compared side-by-side in 360° views with previously reported microsurgical approaches. These 3D models were then used in conjunction with topographic data to guide cadaveric dissection steps. RESULTS: There are two general surgical routes to thalamic lesions: the subarachnoid transcisternal and transcortical routes. The transcisternal route consists of the following three approaches: 1) anterior interhemispheric transcallosal approach, which exposes the anterior and superior thalamus; 2) posterior interhemispheric transcallosal approach, which exposes the posterosuperior thalamus; and 3) supracerebellar infratentorial approach, which exposes the posteromedial cisternal thalamus and can be extended laterally to approach the posterolateral thalamus by cutting the tentorium. The three transcortical approaches are the 1) superior parietal lobule approach, which exposes the posterosuperior thalamus and is particularly advantageous in the setting of hydrocephalus; 2) transtemporal gyrus approach, which exposes the inferolateral thalamus; and 3) transsylvian transinsular approach, which exposes the lateral thalamus (slightly more superiorly and posteriorly) and is advantageous for pathologies extending laterally into the peduncle, lenticular nucleus, or insula. CONCLUSIONS: Microsurgical approaches to thalamic gliomas continue to be challenging. Nonetheless, safe and effective cisternal, ventricular, and cortical corridors can be developed with thoughtful planning, anatomical understanding, and knowledge of the advantages, risks, and limitations of each approach. In some cases, it is wise to combine these approaches with staged procedures, as the authors demonstrate in Part 2. In Part 1 of this two-part series, they discuss thalamic microsurgical anatomy and illustrate the trajectory and exposures of all six approaches to guide decision-making. Part 2 discusses their thalamic glioma microsurgical case series, which utilizes these microsurgical approaches.

Volumetric and functional connectivity changes of the thalamic nuclei in different stages of Alzheimer's disease.

OBJECTIVE: Memory processes known to be impaired in Alzheimer's disease (AD) are maintained by a large-scale neurocognitive network with subcortical components, including the thalamus. Therefore, we aimed to examine the volumetric and functional changes of the thalamic nuclei at different scales across AD stages. METHODS: MRI data of patients diagnosed with 20 AD dementia (ADD), 30 amnestic mild cognitive impairment (MCI), and 30 subjective cognitive impairment (SCI) were used. Volumetric and functional connectivity analyzes were performed by dividing the thalamus into anterior, medial, posterior, lateral and intralaminar nucleus groups and their specific subnuclei. RESULTS: In the course of AD, the volume of the medial group nuclei, especially the mediodorsal medial magnocellular (MDm) nucleus, decreases. Medial group nuclei and MDm functional connectivity with frontal areas were decreased both in ADD and MCI compared to SCI group, while both of them increased their functional connectivity with visual areas in the ADD group compared to the MCI group. CONCLUSIONS: Our study suggests that the medial group of the thalamus, and specifically the MDm, may be affected in AD. SIGNIFICANCE: Specific thalamic nuclei may be a critical anatomical region for investigating structural and functional changes in AD.

The role of the mediodorsal thalamus in chemosensory preference and consummatory behavior in rats.

Experience plays a pivotal role in determining our food preferences. Consuming food generates odor-taste associations that shape our perceptual judgements of chemosensory stimuli, such as their intensity, familiarity, and pleasantness. The process of making consummatory choices relies on a network of brain regions to integrate and process chemosensory information. The mediodorsal thalamus is a higher-order thalamic nucleus involved in many experience-dependent chemosensory behaviors, including olfactory attention, odor discrimination, and the hedonic perception of flavors. Recent research has shown that neurons in the mediodorsal thalamus represent the sensory and affective properties of experienced odors, tastes, and odor-taste mixtures. However, its role in guiding consummatory choices remains unclear. To investigate the influence of the mediodorsal thalamus in the consummatory choice for experienced odors, tastes, and odor-taste mixtures, we pharmacologically inactivated the mediodorsal thalamus during 2-bottle brief-access tasks. We found that inactivation altered the preference for specific odor-taste mixtures, significantly reduced consumption of the preferred taste and increased within-trial sampling of both chemosensory stimulus options. Our results show that the mediodorsal thalamus plays a crucial role in consummatory decisions related to chemosensory preference and attention.

Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain.

Central post-stroke pain (CPSP) is a chronic pain resulting from a lesion in somatosensory pathways. Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) that target the primary motor cortex (M1), have shown promise for the treatment of CPSP. High-frequency (Hf) rTMS exhibits analgesic effects compared to low-frequency (Lf) rTMS; however, its analgesic mechanism is unknown. We aimed to elucidate the mechanism of rTMS-induced analgesia by evaluating alterations of tactile functional magnetic resonance imaging (fMRI) due to Hf- and Lf-rTMS in a CPSP monkey model. Consistent with the patient findings, the monkeys showed an increase in pain threshold after Hf-rTMS, which indicated an analgesic effect. However, no change after Lf-rTMS was observed. Compared to Lf-rTMS, Hf-rTMS produced enhanced tactile-evoked fMRI signals not only in M1 but also in somatosensory processing regions, such as the primary somatosensory and midcingulate cortices. However, the secondary somatosensory cortex (S2) was less active after Hf-rTMS than after Lf-rTMS, suggesting that activation of this region was involved in CPSP. Previous studies showed pharmacological inhibition of S2 reduces CPSP-related behaviors, and the present results emphasize the involvement of an S2 inhibitory system in rTMS-induced analgesia. Verification using the monkey model is important to elucidate the inhibition system.

Trans-temporal trans-choroidal resection of thalamic and thalamopeduncular tumors: how I do it.

BACKGROUND:  Surgical resection is the cornerstone of treatment for low-grade tumors, albeit total excision is beneficial. As the thalamus is surrounded by vital neurovascular system, lesions here present a surgical challenge. METHOD: This article aims to demonstrate the trans-temporal, trans-choroidal fissure approach's effective surgical therapy on patients with thalamic lesions. With this approach, we were able to remove the tumor completely in three patients and almost completely in six more. Here we discuss a few technical details and potential hazards of the procedure with an operative video. CONCLUSION: This approach  provides excellent access to the deep areas of brain.

Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed. Also, we aimed to determine the relationship between cognitive performance and MRI-based outcomes in these matched cohorts. The Comprehensive Assessment of Severely Affected Multiple Sclerosis study was carried out at the University at Buffalo and the Boston Home, a skilled nursing facility in Dorchester, MA. Inclusion criteria were age 30-80 years and expanded disability status scale 3.0-6.5 for community-dwelling and 7.0-9.5 for skilled nursing facility people with multiple sclerosis. The cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis consisting of Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test-2nd edition along with Auditory Test of Processing Speed, Paced Auditory Serial Addition Test-3 second and Controlled Oral Word Association Test. MRI scans were retrospectively collected and analysed for lesion and volumetric brain measurements. The rate of completion and performance of the cognitive tests was compared between the groups, and the relationship with MRI measures was determined using sex, age and years of education-adjusted linear regression models. Significantly greater percentage of the severe multiple sclerosis group completed Auditory Test of Processing Speed when compared with the current gold standard of Symbol Digit Modalities Test (93.2% versus 65.9%). Severe progressive multiple sclerosis had worse cognitive performance in all cognitive domains with greatest differences for cognitive processing speed (Symbol Digit Modalities Test > Paced Auditory Serial Addition Test-3 second > Auditory Test of Processing Speed, Cohen's d < 2.13, P < 0.001), learning and memory (Cohen's d < 1.1, P < 0.001) and language (Controlled Oral Word Association Test with Cohen's d = 0.97, P < 0.001). Multiple cognitive domains were significantly associated with lower thalamic (standardized ß < 0.419, P < 0.006) and cortical (standardized ß < 0.26, P < 0.031) volumes. Specially designed (auditory) cognitive processing speed tests may provide more sensitive screening of cognitive function in severe progressive multiple sclerosis. The cognitive profile of severe multiple sclerosis is proportional to their physical outcomes and best explained by decreased grey matter volume.

The effect of preterm birth on thalamic development based on shape and structural covariance analysis.

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

Local activation of CB1 receptors by synthetic and endogenous cannabinoids dampens burst firing mode of reticular thalamic nucleus neurons in rats under ketamine anesthesia.

The reticular thalamic nucleus (RTN) is a thin shell that covers the dorsal thalamus and controls the overall information flow from the thalamus to the cerebral cortex through GABAergic projections that contact thalamo-cortical neurons (TC). RTN neurons receive glutamatergic afferents fibers from neurons of the sixth layer of the cerebral cortex and from TC collaterals. The firing mode of RTN neurons facilitates the generation of sleep-wake cycles; a tonic mode or desynchronized mode occurs during wake and REM sleep and a burst-firing mode or synchronized mode is associated with deep sleep. Despite the presence of cannabinoid receptors CB1 (CB1Rs) and mRNA that encodes these receptors in RTN neurons, there are few works that have analyzed the participation of endocannabinoid-mediated transmission on the electrical activity of RTN. Here, we locally blocked or activated CB1Rs in ketamine anesthetized rats to analyze the spontaneous extracellular spiking activity of RTN neurons. Our results show the presence of a tonic endocannabinoid input, since local infusion of AM 251, an antagonist/inverse agonist, modifies RTN neurons electrical activity; furthermore, local activation of CB1Rs by anandamide or WIN 55212-2 produces heterogeneous effects in the basal spontaneous spiking activity, where the main effect is an increase in the spiking rate accompanied by a decrease in bursting activity in a dose-dependent manner; this effect is inhibited by AM 251. In addition, previous activation of GABA-A receptors suppresses the effects of CB1Rs on reticular neurons. Our results show that local activation of CB1Rs primarily diminishes the burst firing mode of RTn neurons.

Advancing thalamic neuromodulation in epilepsy: Bridging adult data to pediatric care.

Thalamic neuromodulation has emerged as a treatment option for drug-resistant epilepsy (DRE) with widespread and/or undefined epileptogenic networks. While deep brain stimulation (DBS) and responsive neurostimulation (RNS) depth electrodes offer means for electrical stimulation of the thalamus in adult patients with DRE, the application of thalamic neuromodulation in pediatric epilepsy remains limited. To address this gap, the Neuromodulation Expert Collaborative was established within the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Special Interest Group. In this expert review, existing evidence and recommendations for thalamic neuromodulation modalities using DBS and RNS are summarized, with a focus on the anterior (ANT), centromedian(CMN), and pulvinar nuclei of the thalamus. To-date, only DBS of the ANT is FDA approved for treatment of DRE in adult patients based on the results of the pivotal SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) study. Evidence for other thalamic neurmodulation indications and targets is less abundant. Despite the lack of evidence, positive responses to thalamic stimulation in adults with DRE have led to its off-label use in pediatric patients. Although caution is warranted due to differences between pediatric and adult epilepsy, the efficacy and safety of pediatric neuromodulation appear comparable to that in adults. Indeed, CMN stimulation is increasingly accepted for generalized and diffuse onset epilepsies, with recent completion of one randomized trial. There is also growing interest in using pulvinar stimulation for temporal plus and posterior quadrant epilepsies with one ongoing clinical trial in Europe. The future of thalamic neuromodulation holds promise for revolutionizing the treatment landscape of childhood epilepsy. Ongoing research, technological advancements, and collaborative efforts are poised to refine and improve thalamic neuromodulation strategies, ultimately enhancing the quality of life for children with DRE.

Stroke Mimicking Symptoms and Consequences of Alcohol Intoxication: A Case Report.

A 41-year-old Black male with a history of hypertension was involved in a car accident, after which he exhibited symptoms such as slow and incoherent speech, unstable gait, dizziness, drowsiness, slow thinking, and loss of strength in his limbs. Despite multiple negative alcohol tests, his symptoms mimicked those of acute alcohol intoxication. Upon presentation to the emergency room, physical examination and brain imaging revealed a right anterior thalamic ischemic infarction. He was discharged completely recovered after two days without sequelae. This case underscores the importance of considering stroke as a differential diagnosis in patients presenting with symptoms similar to alcohol intoxication, particularly in hypertensive individuals.

Thalamic H3K27M altered diffuse midline gliomas: Clinicopathological and outcome analysis.

INTRODUCTION: Diffuse midline glioma (DMG) is a relatively new entity which was introduced in the fourth edition of the WHO classification of CNS tumours in 2016 and later underwent revision in 2021. It is an infiltrative glioma arising from midline structures, viz., thalamus, spine, and brainstem. Current literature on DMG is based majorly on brainstem lesions, and DMGs arising elsewhere remain unexplored. In our study, we have discussed our experience with thalamic DMGs. METHODOLOGY: This is a retrospective observational study of all patients with histopathologically proven DMG H3K27M altered, arising in the thalamus from 2018 to 2022. Clinical, neuroimaging, and pathology were re-reviewed, and prognostic factors for 3 months, 6 months, and overall survival (OS) were analyzed for all patients. RESULTS: There were 89 patients- 64 adults and 25 pediatric patients with thalamic DMG. The median age at presentation was 24 years. Raised ICP followed by limb weakness were the most common presenting complaints. Stereotactic biopsy was performed in 64 (71.9 %) patients and surgical decompression in 25 (28.1 %) patients. CSF diversion was required in 53 (59.6 %) patients. Median survival was 8 months in adults and 7 months in pediatric (p-value: 0.51). Raised ICP and TP53 mutation were prognostic factors in pediatric population. Radiotherapy with or without chemotherapy improved survival (p-value- <0.01). CONCLUSION: Thalamic DMGs have a poor prognosis which is comparable to brainstem DMGs. Radiotherapy improves survival in these patients. However, the disease remains an enigma and further work delving into its molecular characterization should be encouraged.

Contralateral interhemispheric transcallosal transchoroidal approach to a thalamic glioma: illustrative case.

BACKGROUND: Thalamic lesions located in the floor of the lateral ventricle pose significant surgical challenges, given their proximity to critical neurovascular structures. Transcortical approaches are often limited by risks of injuring the eloquent cortex and nearby vessels. Furthermore, lesions extending into the third ventricle further impede accessibility. The corticospinal tract (CST), situated close to the thalamus, presents a major obstacle. Diffusion tensor imaging plays a crucial role in overcoming these challenges by accurately delineating the CST's location relative to the lesion, enabling surgeons to plan minimally invasive and safe access. OBSERVATIONS: A 32-year-old female presented with progressive right-sided hemiparesis over several days. Magnetic resonance imaging revealed a cystic ring-enhancing thalamic lesion extending into the third ventricle. While supine, the patient underwent surgery via a right pericoronal parasagittal craniotomy followed by a contralateral interhemispheric transcallosal transchoroidal approach. LESSONS: This case exemplifies the utility of the contralateral interhemispheric transcallosal approach for treating thalamic lesions, particularly those extending into the third ventricle. This minimally invasive approach minimizes retraction of the eloquent cortex and reduces the risk of neurovascular injury, potentially leading to improved surgical outcomes and faster recovery.

Antinociceptive role of the thalamic dopamine D3 receptor in descending modulation of intramuscular formalin-induced muscle nociception in a rat model of Parkinson's disease.

Pain in Parkinson's disease (PD) has been validated as one of the major non-motor dysfunctions affecting the quality of life and subsequent rehabilitation. In the present study, we investigated the role of the dopamine D3 receptor in the thalamic mediodorsal (MD) and ventromedial (VM) nuclei mediated descending control of nociception and intramuscular (i.m.) 2.5% formalin-induced persistent muscle nociception. Paw withdrawal reflexes were measured in naive rats and rats subjected to PD induced by unilateral microinjection of 6 µg 6-OHDA into the rat striatum. Formalin-induced muscle nociception in phase 1, inter-phase, and phase 2 was significantly greater in PD rats compared to naive and vehicle-treated rats (P ˂ 0.001). PD rats exhibited bilaterally mechanical hyperalgesia and heat hypoalgesia in formalin-induced muscle nociception. Microinjection of SK609, a dopamine D3 receptor agonist, at various doses (2.5-7.5 nmol/0.5 µl) into the thalamic VM nucleus dose-dependently prolonged heat-evoked paw withdrawal latencies in both naive and PD rats. Administration of SK609 to either the MD or VM nuclei had no effect on noxious mechanically evoked paw withdrawal reflexes. Pre-treatment of the thalamic MD nucleus with SK609 significantly attenuated formalin-induced nociception, and reversed mechanical hyperalgesia, but not heat hypoalgesia. Pre-treatment of the thalamic VM nucleus with SK609 inhibited formalin-induced nociception in the late phase of phase 2 (30-75 min) and heat hypoalgesia, but not mechanical hyperalgesia (P < 0.05). It is suggested that the dopamine D3 receptors in the thalamus play an antinociceptive role in the descending modulation of nociception. Activation of D3 receptors within the thalamic MD and VM nuclei attenuates descending facilitation and enhances descending inhibition in rats during PD.

When the diagnosis is in the patient's hand and in the neurologist's eye.

The objective of this study was to encompass current knowledge about pathophysiological mechanisms of those specific hand postures or deformities caused by central nervous system disorders. In the era of high-resolution neuroimaging and molecular biology, clinicians are progressively losing confidence with neurological examination. Careful hand observation is of key importance in order to differentiate neurological from non-neurological conditions, central from peripheral aetiologies, and organic from functional disorders. Localizing the potential anatomical site is essential to properly conduct subsequent exams. We provided a practical guide for clinicians to recognize hand patterns caused by central nervous system disorders, avoiding mimicking conditions, thus optimizing and prompting the diagnostic pathway.

GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol- and isoflurane-mediated general anesthesia.

BACKGROUND: The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. METHODS: We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. RESULTS: c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. CONCLUSION: Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.

Two Distinct Neuronal Populations in the Rat Parafascicular Nucleus Oppositely Encode the Engagement in Stimulus-driven Reward-seeking.

BACKGROUND: The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. METHODS: The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. RESULTS: We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons. CONCLUSION: Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.

Addition of quantitative MRI to the routine clinical care of patients with multiple sclerosis-Results from the MAGNON project.

BACKGROUND: The revised Lublin classification offers a framework for categorizing multiple sclerosis (MS) according to the clinical course and imaging results. Diagnosis of secondary progressive MS (SPMS) is often delayed by a period of uncertainty. Several quantitative magnetic resonance imaging (qMRI) markers are associated with progressive disease states, but they are not usually available in clinical practice. METHODS: The MAGNON project enrolled 629 patients (early relapsing-remitting MS (RRMS), n = 51; RRMS with suspected SPMS, n = 386; SPMS, n = 192) at 55 centers in Germany. Routine magnetic resonance imaging (MRI) scans at baseline and after 12 months were analyzed using a centralized automatic processing pipeline to quantify lesions and normalized brain and thalamic volume. Clinical measures included relapse activity, disability, and MS phenotyping. Neurologists completed questionnaires before and after receiving the qMRI reports. RESULTS: According to the physicians' reports, qMRI results changed their assessment of the patient in 31.8% (baseline scan) and 27.6% (follow-up scan). For ∼50% of patients with RRMS with suspected SPMS, reports provided additional information that the patient was transitioning to SPMS. In >25% of all patients, this information influenced the physicians' assessment of the patient's current phenotype. However, actual changes of treatment were reported only in a minority of these patients. CONCLUSIONS: The MAGNON results suggest that standardized qMRI reports may be integrated into the routine clinical care of MS patients and support the application of the Lublin classification as well as treatment decisions. The highest impact was reported in patients with suspected SPMS, indicating a potential to reduce diagnostic uncertainty.

MULTIPLE DISTINCT TIMESCALES OF RAPID SENSORY ADAPATION IN THE THALAMOCORTICAL CIRCUIT.

Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world, yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multi-electrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing.