Search

Brain‘s neuro protection is clearly the new frontier in movement disorder research and therapy. The longterm clinical studies have so far failed to prove that high-frequency stimulation has been able to slow down the evolution of the disease. So called e a r l y s t i m clinical p r o t o c o l s have only proven that it was safe to induce or stimuli sub thalamic nucleus S T N much earlier than it was so far accepted. At the experimental level, M P T P - treated monkeys, high-frequency stimuli of the S T N could protect neurons in the sub stantia nigra. To test this scientific rationale/hypothesis in humans, one would need to perform S T N induced stimuli at the very beginning of the disease, which is not easily ethically sustainable given the surgical risk, even if low, in patients who are still minimally impaired by the disease. There have been so many advancements in computing capabilities; big data management; miniaturization of electronics, devices and batteries; and new sources of energy compatible with implantation of biological devices and fuel cells. More recently, there has been an explosion of biological imaging at the nano level as well as whole-brain imaging. It is impossible to generate a reasonable picture of future technological development without being sure to be wrong. The consequence of that is that when building projects and setting new protocols as well as imagining new tools and devices, we should be confident that what has not yet been developed will eventually be created. In this article we the author explained the present past and future Parkinson‘s disease prediction. Keywords: SubstantiaNigra (SN), Principal-component (PC), STN.

Many studies exist of thalamocortical synapses in primary sensory cortex, but much less in known about higher-order thalamocortical projections to higher-order cortical areas. We begin to address this gap using genetic labeling combined with large volume serial electron microscopy (i.e., "connectomics") to study the projection from the thalamic posterior medial nucleus to the secondary somatosensory cortex in a mouse. We injected into this thalamic nucleus a cocktail combining a cre-expressing virus and one expressing cre-dependent ascorbate peroxidase that provides an electron dense cytoplasmic label. This "intersectional" viral approach specifically labeled thalamocortical axons and synapses, free of retrograde labeling, in all layers of cortex. Labeled thalamocortical synapses represented 14% of all synapses in the cortical volume, consistent with previous estimates of first-order thalamocortical inputs. We found that labeled thalamocortical terminals, relative to unlabeled ones: were larger, were more likely to contain a mitochondrion, more frequently targeted spiny dendrites and avoided aspiny dendrites, and often innervated larger spines with spine apparatuses, among other differences. Furthermore, labeled terminals were more prevalent in layers 2/3 and synaptic differences between labeled and unlabeled terminals were greatest in layers 2/3. The laminar differences reported here contrast with reports of first-order thalamocortical connections in primary sensory cortices where, for example, labeled terminals were larger in layer 4 than layers 2/3 (Viaene et al., 2011a). These data offer the first glimpse of higher-order thalamocortical synaptic ultrastructure and point to the need for more analyses, as such connectivity likely represents a majority of thalamocortical circuitry.

Magnetic resonance‐guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas‐based stereotactic approach. We developed a new patient‐specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter‐white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim‐ablation overlap) and 1‐month post‐treatment clinical outcome. We then defined a group‐based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1‐month clinical outcome (r = −.57, p = .03), in contrast to the standard target (r = −.23, p = .44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor‐associated center within Vim and potentially improving MRgFUS treatment for ET., Magnetic resonance‐guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET); a patient‐specific mapping of the upper extremity tremor‐associated center within Vim is an unmet need in present‐day MRgFUS treatment for ET. Using high quality preoperative and postoperative WMnMPRAGE imaging, state‐of‐the‐art nonlinear registration, segmentation of thalamic nuclei and FUS ablation characteristics, and probabilistic lesion calculations using a cohort of ET patients, we discovered a novel location within the Vim that is associated with upper extremity tremor reduction. This is a powerful example of human brain mapping that cannot be achieved in healthy subjects, yet still involves entirely noninvasive imaging and therapeutic modalities.

Whisker detection is crucial to adapt to the environment for some animals, but how the nervous system processes and integrates whisker information is still an open question. It is well-known that two main parallel pathways through Ventral posteromedial thalamic nucleus (VPM) ascend to the barrel cortex, and classical theory suggests that the cross-talk from trigeminal nucleus interpolaris (Sp5i) to principal nucleus (Pr5) between the main parallel pathways contributes to the multi-whisker integration in barrel columns. Moreover, some studies suggest there are other cross-streams between the parallel pathways. To confirm their existence, in this study we used a dual-viral labeling strategy and high-resolution, large-volume light imaging to get the complete morphology of individual VPM neurons and trace their projections. We found some new thalamocortical projections from the ventral lateral part of VPM (VPMvl) to barrel columns. In addition, the retrograde-viral labeling and imaging results showed there were the large trigeminothalamic projections from Sp5i to the dorsomedial section of VPM (VPMdm). Our results reveal new cross-streams between the parallel pathways through VPM, which may involve the execution of multi-whisker integration in barrel columns.

Midline thalamic nuclei play a critical role in cognitive functions such as memory, decision-making and spatial navigation, by facilitating communication between the many brain regions involved in these processes. One canonical feature of thalamic interactions with the cortex or hippocampus appears to be that the thalamus receives input from, and projects to, excitatory neurons. Thalamic nucleus reuniens (NRe) is located on the midline and is viewed primarily as a relay from prefrontal cortex to hippocampal and entorhinal areas, although these connections are poorly defined at the cellular and synaptic level. Using electrophysiology and monosynaptic circuit-tracing, we found that pyramidal cells in CA1 receive no direct input from NRe. This contrasts starkly with prefrontal cortex, subiculum and entorhinal cortex, and indicates that NRe inputs to CA1 primarily drive local inhibition and not excitation they do in the other regions. The NRe to CA1 projection is thus a unique thalamic projection and as such is raising important questions about the function of NRe-mediated prefrontal control of the hippocampus.

Contains fulltext : 237073.pdf (Publisher’s version ) (Closed access) Introduction: The thalamus, a heterogeneous brain structure, is involved in the generation of sleep related thalamo-cortical oscillations. Higher-order nuclei might possess a distinct function compared to first-order nuclei in brain communication. Here it is investigated whether this distinction can also be found during the process of falling asleep and deepening of slow-wave-sleep. Methods: A non-linear version of Granger-Causality was used to describe changes in directed network activity between somatosensory-cortex and rostral and caudal reticular-thalamic-nucleus, the higher-order posterior- and anterior- thalamic nuclei and the first-order ventral-postero-medial thalamic nucleus as assessed in LFP recordings acquired during passive-wakefulness (PW), light and deep slow-wave sleep (LSWS, DSWS) in freely behaving rats. Surrogate statistics were used to assess significance. Results: Decreases in cortico-thalamo-cortical couplings were found. In contrast, multiple increases in intrathalamic couplings were observed. In particular, the rostral reticular-thalamic-nucleus (rRTN) increased its inhibition on the anterior (ATN) from PW to LSWS, and this was further strengthened from LSWS to DSWS. The caudal reticular-thalamic-nucleus (cRTN) increased its coupling to VPM and PO from PW to LSWS, but the coupling from cRTN to VPM weakened at the transition from LSWS to DSWS while its coupling to PO strengthened. Furthermore, intra-RTN coupling from PW to LSWS was differently changed compared to the change from LSWS to DSWS. Discussion: It can be inferred that higher-order (ATN and PO) and first-order nuclei (VPM) are differentially inhibited during DSWS, which might be relevant for a proper functioning of sleep related processes. 10 p.

Memory can be challenged by increasing both its required duration and the amount of information to be encoded, namely the memory load. The dorsal hippocampus (dHP) has been involved in memory consolidation, which is the stabilization of a trace from short-term (STM) to long-term memory (LTM), as well as in the ability to process high information load. However, how memory load influences memory consolidation, and the underlying neural mechanisms, are yet unknown. To address this question, we used male and female mice that, despite having in our Different Object recognition Task (DOT) the same STM capacity of 6 objects, spontaneously show differences in the number of objects directly transferred to LTM, when tested over longer delays. Males memorize all 6 objects encoded, while females remember only up to 4, both at 1 and 24 h delays. Interestingly, males activate more the dHP (as measured by c-Fos expression), while females the thalamic nucleus reuniens (RE). Optogenetic inhibition of the RE-dHP pathway during off-line memory consolidation favors 6-object LTM retention in females by removing inhibitory control over dHP activation, while chemogenetic RE-activation impairs it in males. Our data represent a first demonstration of a sub-cortical control of dHP recruitment, that might underlie its sex-dependent activation during incidental memory, with potential also for clinical application.

The medial pulvinar (PM) is a multimodal associative thalamic nucleus, recently evolved in primates. PM participates in integrative and modulatory functions, including directed attention, and consistently exhibits alterations in disorders such as schizophrenia and autism. Despite essential cognitive functions, the cortical inputs to the PM have not been systematically investigated. To date, less than 20 cortices have been demonstrated to project to PM. The goal of this study was to establish a comprehensive map of the cortical afferents to PM in the marmoset monkey. Using a magnetic resonance imaging-guided injection approach, we reveal 62 discrete cortices projecting to the adult marmoset PM. We confirmed previously reported connections and identified further projections from discrete cortices across the temporal, parietal, retrosplenial-cingulate, prefrontal, and orbital lobes. These regions encompass areas recipient of PM efferents, demonstrating the reciprocity of the PM-cortical connectivity. Moreover, our results indicate that PM neurones projecting to distinct cortices are intermingled and form multimodal cell clusters. This microunit organization, believed to facilitate cross-modal integration, contrasts with the large functional subdivisions usually observed in thalamic nuclei. Altogether, we provide the first comprehensive map of PM cortical afferents, an essential stepping stone in expanding our knowledge of PM and its function.

Parkinson’s Disease ( PD ) is a chronic neurodegenerative disease . It’s cardinal features are resting tremor, Rigidity, Akinesia and postural instability. Idiopathic Parkinson’s disease develops mainly due to degeneration of Dopaminergic neurons of Substantia Nigra. The role of Subthalamic Nucleus ( STN ) in the development of Parkinsonian Tremmor and other cardinal features is not completely understood yet. However previous studies in monkeys , administration of MPTP ( 1-methyl-4-phenyl- 1.2.3.6.-tetrahydropyridine ) proved that sub thalamic nucleus has a direct role in the development of Parkinsonian tremor and other features. We used no Micro Electrode Recording (MER) system,only studied clinically that Parkinsonian tremor stopped immediately after placement of electrode and same thing happened after micro stimulation of the sensorymotor region of the sub thalamic nucleus .Then high frequency deep brain stimulation ( DBS ) of these same four patients were assessed six months after surgery which led to a significant reduction of Parkinsonian tremor as well as other cardinal features of PD ( p< 0.001 ) . Both postural and resting tremor disappeared completely in three cases and significantly reduced in one case Bang. J Neurosurgery 2019; 9(1): 78-83

Higher-order visual thalamus communicates broadly and bi-directionally with primary and extrastriate cortical areas in various mammals. In primates, the pulvinar is a topographically and functionally organized thalamic nucleus that is largely dedicated to visual processing. Still, a more granular connectivity map is needed to understand the role of thalamocortical loops in visually guided behavior. Similarly, the secondary visual thalamic nucleus in mice (the lateral posterior nucleus, LP) has extensive connections with cortex. To resolve the precise connectivity of these circuits, we first mapped mouse visual cortical areas using intrinsic signal optical imaging and then injected fluorescently tagged retrograde tracers (cholera toxin subunit B) into retinotopically-matched locations in various combinations of seven different visual areas. We find that LP neurons representing matched regions in visual space but projecting to different extrastriate areas are found in different topographically organized zones, with few double-labeled cells (~4–6%). In addition, V1 and extrastriate visual areas received input from the ventrolateral part of the laterodorsal nucleus of the thalamus (LDVL). These observations indicate that the thalamus provides topographically organized circuits to each mouse visual area and raise new questions about the contributions from LP and LDVL to cortical activity.

Flight, an active fear response to imminent threat, is dependent on the rapid risk assessment of sensory information processed by the cortex. The thalamic reticular nucleus (TRN) filters information between the cortex and the thalamus, but whether it participates in the regulation of flight behavior remains largely unknown. Here, we report that activation of parvalbumin-expressing neurons in the limbic TRN, but not those in the sensory TRN, mediates flight. Glutamatergic inputs from the cingulate cortex (Cg) selectively activate the limbic TRN, which in turn inhibits the intermediodorsal thalamic nucleus (IMD). Activation of this Cg→limbic TRN→IMD circuit results in inhibition of the IMD and produces flight behavior. Conversely, removal of inhibition onto the IMD results in more freezing and less flight, suggesting that the IMD may function as a pro-freeze center. Overall, these findings reveal a novel corticothalamic circuit through the TRN that controls the flight response.

ObjectiveDeep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (Vim) is established for medically refractory severe essential tremor (ET), but long-term efficacy is controversial.MethodsTwenty patients with ET with DBS had standardized video-documented examinations at baseline, in the stimulation-on condition at short term (13.1 ± 1.9 months since surgery, mean ± SEM), and in the stimulator switched on and off (stim-ON/OFF) at long term; all assessments were done between 32 and 120 months (71.9 ± 6.9 months) after implantation. The primary outcome was the Tremor Rating Scale (TRS) blindly assessed by 2 trained movement disorder neurologists. Secondary outcomes were TRS subscores A, B, and C; Archimedes spiral score; and activities of daily living score. At long-term follow-up, tremor was additionally recorded with accelerometry. The rebound effect after switching the stimulator off was assessed for 1 hour in a subgroup.ResultsTremor severity worsened considerably over time in both in the nonstimulated and stimulated conditions. Vim-DBS improved the TRS in the short term and long term significantly. The spiral score and functional measures showed similar improvements. All changes were highly significant. However, the stimulation effect was negatively correlated with time since surgery (ρ = −0.78, p < 0.001). This was also true for the secondary outcomes. Only one-third of the patients had a rebound effect terminated 60 minutes after the stimulator was switched off. Long-term worsening of the TRS was more profound during stim-ON than in the stim-OFF condition, indicating habituation to stimulation.ConclusionVim-DBS loses efficacy over the long term. Efforts are needed to improve the long-term efficacy of Vim-DBS.Classification of evidenceThis study provides Class IV evidence that for patients with medically refractory severe ET, the efficacy of Vim-DBS severely decreases over 10 years.

Perception of aversive sensory stimuli such as pain and innate threat cues is essential for animal survival. The amygdala is critical for aversive sensory perception, and it has been suggested that multiple parallel pathways independently relay aversive cues from each sensory modality to the amygdala. However, a convergent pathway that relays multisensory aversive cues to the amygdala has not been identified. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafasicular thalamic nucleus (SPFp) are necessary and sufficient for affective-motivational pain perception by forming a spino-thalamo-amygdaloid pain pathway. In addition, we find that this thalamic CGRP pain pathway, together with well-known parabrachio-amygdaloid CGRP pain pathway, relays multisensory innate threat cues to the amygdala. The discovery of unified pathways that collectively gate aversive sensory stimuli from all sensory modalities may provide critical circuit-based insights for developing therapeutic interventions for affective pain- and innate fear-related disorders.

Vocal communication is important for reproductive success in birds. Conspecific vocalization of birds is processed in the auditory system from ear to higher-order auditory regions in the telencephalon, including the caudomedial nidopallium (NCM). Higher-order auditory regions are involved in the perception of vocal communication in songbirds and nonsongbirds. In a nonsongbird parrot, the NCM of females is involved in the perception of song complexity, which has been considered an intersexually selected trait. Social information is thought to converge on the hypothalamus and is then transduced into a reproductive endocrine response. In another nonsongbird dove, the information from the courtship call is relayed to the hypothalamic neuroendocrine cells through the auditory thalamic nucleus. Together, the existing studies suggest that auditory inputs to higher-order auditory regions and the hypothalamic-pituitary-gonadal (HPG) axis are important for nonsongbird reproduction. It remains unclear whether the HPG axis receives auditory information from higher-order auditory regions.

The lateral habenula (LHb) is hyperactive in depression, and thus potentiating inhibition of this structure makes an interesting target for future antidepressant therapies. However, the circuit mechanisms mediating inhibitory signalling within the LHb are not well-known. We addressed this issue by studying LHb neurons expressing either parvalbumin (PV), neuron-derived neurotrophic factor (Ndnf) or somatostatin (SOM), three markers of particular sub-classes of neocortical inhibitory neurons. While we report that Ndnf is not representative of any particular sub-population of LHb neuron, we find that both PV and SOM are expressed by physiologically distinct sub-classes. Furthermore, we describe multiple sources of inhibitory input to the LHb arising from both local PV-positive neurons, and from PV-positive neurons in the medial dorsal thalamic nucleus, and from SOM-positive neurons in the ventral pallidum. These findings hence provide new insight into inhibitory control within the LHb, and highlight that this structure is more neuronally diverse than previously thought.SummaryThe lateral habenula receives inhibitory input from three distinct sources: from local PV-positive neurons, from PV-positive neurons in the medial dorsal thalamic nucleus (MDT); and from SOM-positive neurons in the ventral pallidum (VP).Significance statementThe circuitry by which inhibitory signalling is processed within the lateral habenula is currently not well understood; yet this is an important topic as inhibition of the lateral habenula has been shown to have antidepressant efficacy. We therefore investigated inhibitory signalling mechanisms within the lateral habenula by studying input neurons expressing markers commonly associated with inhibitory identity. We identity sources of inhibitory input from both local neurons, and arising from neurons in the medial dorsal thalamic nucleus and ventral pallidum.ContributionsJ.F.W. performed the experiments. R.V. contributed to experiments. J.F.W. analysed the data. K.B. and P.W. designed and performed the in situ hybridisation experiments. C.W. designed and supervised the study, and helped J.F.W write the manuscript. R.V. and S.S. contributed to the manuscript and discussions.

In the rodent whisker system, it is well assumed that VPM and POm encode stimulations of the contralateral whisker pad. However, during tactile exploration whiskers are usually stimulated bilaterally. Accordingly, the integration of tactile information from the two sides of the body seems to be fundamental in the processing of these events. Here, to investigate whether POm could be able to codify these bilateral dynamics, whisker-evoked responses in this thalamic nucleus were examined by in vivo extracellular recordings in anesthetized rats using contralateral and ipsilateral stimuli. Strikingly, we found that POm is also able to respond to tactile stimulation of ipsilateral whiskers. Our findings reveal the implication of POm in the representation of bilateral tactile events by integrating simultaneous signals arising from both whisker pads and demonstrate the implication of the higher-order sensory thalamus in the encoding of bilateral sensory events. This can have important implications in bilateral perceptual function.

Investigating neural activity from a global brain perspective in-vivo has been in the domain of functional Magnetic Resonance Imaging (fMRI) over the past few decades. The intricate neurovascular couplings that govern fMRI's blood-oxygenation-level-dependent (BOLD) functional contrast are invaluable in mapping active brain regions, but they also entail significant limitations, such as non-specificity of the signal to active foci. Diffusion-weighted functional MRI (dfMRI) with relatively high diffusion-weighting strives to ameliorate this shortcoming as it offers functional contrasts more intimately linked with the underlying activity. Insofar, apart from somewhat smaller activation foci, dfMRI's contrasts have not been convincingly shown to offer significant advantages over BOLD-driven fMRI, and its activation maps relied on significant modelling. Here, we study whether dfMRI could offer a better representation of neural activity in the thalamocortical pathway compared to its (spin-echo (SE)) BOLD counterpart. Using high-end forepaw stimulation experiments in the rat at 9.4 T, and with significant sensitivity enhancements due to the use of cryocoils, we show for the first time that dfMRI signals exhibit layer specificity, and, additionally, display signals in areas devoid of SE-BOLD responses. We find that dfMRI signals in the thalamocortical pathway cohere with each other, namely, dfMRI signals in the ventral posterolateral (VPL) thalamic nucleus cohere specifically with layers IV and V in the somatosensory cortex. These activity patterns are much better correlated (compared with SE-BOLD signals) with literature-based electrophysiological recordings in the cortex as well as thalamus. All these findings suggest that dfMRI signals better represent the underlying neural activity in the pathway. In turn, these advanatages may have significant implications towards a much more specific and accurate mapping of neural activity in the global brain in-vivo., Highlights • dfMRI signals exhibit cortical layer specificity and show anatomically well-defined thalamic activity. • Layer-specific coherence was observed between cortical and sensory thalamic signals using dfMRI. • dfMRI evidences functional signals in sensory thalamus while SE-BOLD signals are absent. • Signal reception with a cryogenic coil facilitates data-driven analyses, obviating complex statistical models. • dfMRI signals appear more intimately linked with underlying activity than their SE[HYPHEN]BOLD counterparts.

The pulvinar, the largest thalamic nucleus in the primate brain, has connections with a variety of cortical areas and is involved in many aspects of higher brain functions. Among cortico-pulvino-cortical systems, the connection between the middle temporal area (MT) and the pulvinar has been thought to contribute significantly to complex motion recognition. Recently, the common marmoset (Callithrix jacchus), has become a valuable model for a variety of neuroscience studies, including visual neuroscience and translational research of neurological and psychiatric disorders. However, information on projections from MT to the pulvinar in the marmoset brain is scant. We addressed this deficiency by injecting sensitive anterograde viral tracers into MT to examine the distribution of labeled terminations in the pulvinar. The injection sites were placed retinotopically according to visual field coordinates mapped by optical intrinsic imaging. All injections produced anterograde terminal labeling, which was densest in the medial nucleus of the inferior pulvinar (PIm), sparser in the central nucleus of the inferior pulvinar, and weakest in the lateral pulvinar. Within each subnucleus, terminations formed separate retinotopic fields. Most labeled terminals were small but these comingled with a few large terminals, distributed mainly in the dorsomedial part of the PIm. Our results further delineate the organization of projections from MT to the pulvinar in the marmoset as forming parallel complex networks, which may differentially contribute to motion processing. It is interesting that the densest projections from MT target the PIm, the subnucleus recently reported to preferentially receive direct retinal projections.

Objective. To investigate the peculiarities of the antidyskinetic effect of stereotactic interventions in ventrointermedial (Vim) thalamic nucleus in patients with Parkinson’s disease (PD). Materials and methods. Ventrointermedial thalamotomy (Vim-thalamotomy) for resistant tremor was performed in 10 patients with initial levodopa-induced dyskinesias (LIDs), which were considered as the secondary symptoms and were not taken into account when selecting the nucleus target (group 1). The study also includes 8 patients with LIDs developed due to disease progression after the Vim-thalamotomy performed earlier (group 2). Results. In group 1 after Vim-thalamotomy, 9 out of 10 patients had LIDs control in the contralateral limbs. A similar clinical observation was found in all 8 patients in group 2: while LIDs manifested on the ipsilateral side of the previously performed Vim-thalamotomy, they did not develop on the contralateral side. Such apparent antidyskinetic effects of our Vim-thalamotomіes contradict contemporary knowledge about the anatomical and pathophysiological features of LIDs. Conclusions. The control of LIDs after Vim-thalamotomy in patients with PD may indicate the afferent pallidal projections of ventrolateral thalamus involvement into the lesion. Combined anti-tremor and antidyskinetic effects are possible with the localization of the stereotactic target 3 mm behind the midcommissural point and/or with the diagonal trajectory of the electrode with an uninsulated tip of 4 mm in length. Appropriate stereotactic coordinates can be recommended for the operation of choice for patients with PD with tremor — LID symptom complex.

Comprising of axial and/or kinetic tremors, essential tremor (ET) is a debilitating and common movement disorder that negatively affects up to 1% of the global population. When patients fail medical therapy, deep brain stimulation (DBS) is one of the current standards of care for medically refractory ET treatment. Using stereotactic methods, surgeons may stimulate the ventral intermediate thalamic nucleus (VIM) and novel targets, such as the posterior subthalamic area and the zona incerta, with long-term benefits and significant tremor reduction. Other alternatives include stereotactic radiosurgery and MRI-guided focused ultrasound (FUS).

Fear and trauma generate some of the longest-lived memories. Despite the corresponding need to understand how such memories can be attenuated, the underlying brain circuits remain unknown. Here, combining viral tracing, neuronal activity mapping, fiber photometry, chemogenetic and closed-loop optogenetic manipulations in mice, we show that the extinction of remote (30-day-old) fear memories depends on thalamic nucleus reuniens (NRe) inputs to the basolateral amygdala (BLA). We found that remote, but not recent (1-day-old), fear extinction activates NRe-to-BLA inputs, which become potentiated upon fear reduction. Furthermore, both monosynaptic NRe-to-BLA and total NRe activity increase shortly before freezing cessation, suggesting that the NRe registers and transmits safety signals to the BLA. Accordingly, pan-NRe and pathway-specific NRe-to-BLA inhibition impairs, whereas their activation facilitates, remote fear extinction. These findings identify the NRe as a crucial BLA regulator for extinction and provide the first functional description of the circuits underlying the attenuation of consolidated fear memories. Silva et al. reveal distinct circuits for the extinction of remote fear memories, with the thalamic nucleus reuniens and its outputs to the basolateral amygdala taking center stage.

Volumes of thalamic nuclei are differentially affected by disease‐related processes including alcoholism and human immunodeficiency virus (HIV) infection. This MRI study included 41 individuals diagnosed with alcohol use disorders (AUD, 12 women), 17 individuals infected with HIV (eight women), and 49 healthy controls (24 women) aged 39 to 75 years. A specialized, high‐resolution acquisition protocol enabled parcellation of five thalamic nuclei: anterior [anterior ventral (AV)], posterior [pulvinar (Pul)], medial [mediodorsal (MD)], and ventral [including ventral lateral posterior (VLp) and ventral posterior lateral (VPl)]. An omnibus mixed‐model approach solving for volume considered the “fixed effects” of nuclei, diagnosis, and their interaction while covarying for hemisphere, sex, age, and supratentorial volume (svol). The volume by diagnosis interaction term was significant; the effects of hemisphere and sex were negligible. Follow‐up mixed‐model tests thus evaluated the combined (left + right) volume of each nucleus separately for effects of diagnosis while controlling for age and svol. Only the VLp showed diagnoses effects and was smaller in the AUD (p = .04) and HIV (p = .0003) groups relative to the control group. In the AUD group, chronic back pain (p = .008) and impaired deep tendon ankle reflex (p = .0005) were associated with smaller VLp volume. In the HIV group, lower CD4 nadir (p = .008) was associated with smaller VLp volume. These results suggest that the VLp is differentially sensitive to disease processes associated with AUD and HIV.

While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p 0.01) and medial occipital lobe in patients versus controls (p 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p 0.05, r = 0.381) and Delayed scores (p 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c-Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well-known feeding-related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding-activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding-activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding-activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding-activated neuronal groups, suggesting that short-loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803-2827, 2016. © 2016 Wiley Periodicals, Inc.

The concept of a rat-robot was initially introduced in 2002, bringing to the field, a novel area of research using modern research into neuroscience and robotics. This paper brings to the table, a study into the method best used for navigation systems in a rat-robot. Current research is epitomized by the use of reward-based spatial navigation, combining the concept of an induced reward sensation as well as a 'virtual touch' sensation to control the movement of the rat-robot. However, such methods are plagued by limitations affecting the success rate as well as preparation procedures which may have varying effects on different rats, even under similar conditions. Hence, this paper studies the stimulation of two different portions of the brain to induce a turning motion within the rat, namely the Ventral Posteromedial (VPM) thalamic nucleus as well as the Barrel-Field (BF) cortex and demonstrates the preferential usage of VPM as the choice use of navigational control in a rat-robot.

The dorsal pulvinar is a thalamic nucleus that remains poorly understood despite being the subject of many studies. Inputs from the superior colliculus ([Benevento and Standage, 1983][1]) and reciprocal connections with parietal ([Hardy and Lynch, 1992][2]; [Gutierrez et al., 2000][3]) and

The centromedian (CM) nucleus is an intralaminar thalamic nucleus that is considered as a potentially effective target of deep brain stimulation (DBS) and ablative surgeries for the treatment of multiple neurological and psychiatric disorders. However, the structure of CM is invisible on the standard T1- and T2-weighted (T1w and T2w) magnetic resonance images, which hamper it as a direct DBS target for clinical applications. The purpose of the current study is to demonstrate the use of quantitative susceptibility mapping (QSM) technique to image the CM within the thalamic region. Twelve patients with Parkinson's disease, dystonia, or schizophrenia were included in this study. A 3D multi-echo gradient recalled echo (GRE) sequence was acquired together with T1w and T2w images on a 3-T MR scanner. The QSM image was reconstructed from the GRE phase data. Direct visual inspection of the CM was made on T1w, T2w, and QSM images. Furthermore, the contrast-to-noise ratios (CNRs) of the CM to the adjacent posterior part of thalamus on T1w, T2w, and QSM images were compared using the one-way analysis of variance (ANOVA) test. QSM dramatically improved the visualization of the CM nucleus. Clear delineation of CM compared to the surroundings was observed on QSM but not on T1w and T2w images. Statistical analysis showed that the CNR on QSM was significantly higher than those on T1w and T2w images. Taken together, our results indicate that QSM is a promising technique for improving the visualization of CM as a direct targeting for DBS surgery.

The pulvinar is primarily referred to for its role in visual processing. However, the 'visual pulvinar' only encompasses the inferior and lateral regions of this complex thalamic nucleus. The remaining medial portion (medial pulvinar, PM) establishes distinct cortical connectivity and has been associated with directed attention, executive functions and working memory. These functions are particularly impaired in neurodevelopmental disorders, including schizophrenia and attention deficit and hyperactivity disorder (ADHD), both of which have been associated with abnormal PM architecture and connectivity. With these disorders becoming more prevalent in modern societies, we review the literature to better understand how the PM can participate in the pathophysiology of cognitive disorders and how a better understanding of the development and function of this thalamic nucleus, which is most likely exclusive to the primate brain, can advance clinical research and treatments.

Medullary dorsal horn (MDH), the homolog of spinal dorsal horn, plays essential roles in processing of nociceptive signals from orofacial region toward higher centers, such as the ventral posteromedial thalamic nucleus (VPM) and parafascicular thalamic nucleus (Pf), which belong to the sensory-discriminative and affective aspects of pain transmission systems at the thalamic level, respectively. In the present study, in order to provide morphological evidence for whether neurons in the MDH send collateral projections to the VPM and Pf, a retrograde double tracing method combined with immunofluorescence staining for substance P (SP), SP receptor (SPR) and Fos protein was used. Fluoro-gold (FG) was injected into the VPM and the tetramethylrhodamine-dextran (TMR) was injected into the Pf. The result revealed that both FG- and TMR-labeled projection neurons were observed throughout the entire extent of the MDH, while the FG/TMR double-labeled neurons were mainly located in laminae I and III. It was also found that some of the FG/TMR double-labeled neurons within lamina I expressed SPR and were in close contact with SP-immunoreactive (SP-ir) terminals. After formalin injection into the orofacial region, 41.4% and 34.3% of the FG/TMR double-labeled neurons expressed Fos protein in laminae I and III, respectively. The present results provided morphological evidence for that some SPR-expressing neurons within the MDH send collateral projections to both VPM and Pf and might be involved in sensory-discriminative and affective aspects of acute orofacial nociceptive information transmission.

Objectives Despite its efficacy in tremor-suppression, the ventral intermediate thalamic (VIM) nucleus has largely been neglected in deep brain stimulation (DBS) for tremor-dominant Parkinson's disease (tdPD). The employment of a parietal approach, however, allows stimulation of VIM and subthalamic nucleus (STN) using one trajectory only and thus constitutes a promising alternative to existing strategies. In the present study, we investigate safety and efficacy of combined lead implantation and stimulation of STN and VIM using a parietal approach. Materials and methods Retrospective analysis of five patients with tdPD was performed who underwent DBS using a parietal approach. Changes in symptom severity, disease-specific health-related quality of life and l-dopa equivalent doses (LED) were evaluated over a total time course of 12 months. Results DBS within both targets yielded significant improvement of parkinsonian symptoms (median: 40.0%, p = 0.04) in the first 6 months of continuous stimulation and remained stable thereafter (median improvement at 12 months: 43.2%, p = 0.07). Sustained improvement of tremor (median at 6 months: 100.0%, p = 0.04; median at 12 months 83.3%, p = 0.04) and quality of life scores (median at 6 months: 29.8%, p = 0.04; median at 12 months: 32.6%, p = 0.04) was noted throughout the follow-up period. No significant change of LEDs was observed by the end of follow-up (median decrease: 2.2%, p = 0.89). Conclusions Simultaneous DBS of VIM and STN using one trajectory is safe, yielding good control of parkinsonian tremors. Further studies, however, are necessary to determine whether a parietal trajectory affords better control over tremor symptoms than established strategies and hence justifies the potential risks associated with the alternative approach.

The fronto-parietal attention network represents attentional priorities and provides feedback about these priorities to sensory cortical areas. Sustained spiking activity in the posterior parietal cortex (PPC) carries such prioritized information, but how this activity is sustained in the absence of feedforward sensory information, and how it is transmitted to the ventral visual cortical pathway, is unclear. We hypothesized that the higher-order thalamic nucleus, the pulvinar, which is connected with both the PPC and ventral visual cortical pathway, influences information transmission within and between these cortical regions. To test this, we simultaneously recorded from the pulvinar, lateral intraparietal area (LIP) and visual cortical area V4 in macaques performing a selective attention task. Here we show that LIP influenced V4 during the delay period of the attention task, and that the pulvinar regulated LIP-V4 information exchange. Pulvino-cortical effects were consistent with the pulvinar supporting sustained activity in LIP. Taken together, these results suggest that pulvinar regulation of cortical functional connectivity generalizes to dorsal and ventral visual cortical pathways. Further, the pulvinar’s role in sustaining parietal delay activity during selective attention implicates the pulvinar in other cognitive processes supported by such delay activity, including decision-making, categorization and oculomotor functions.Significance StatementA network of areas on the brain’s surface, in frontal and parietal cortex, allocate attention to behaviorally relevant information around us. Such areas in parietal cortex show sustained activity during maintained attention and transmit behaviorally relevant information to visual cortical areas to enhance sensory processing of attended objects. How this activity is sustained and how it is transmitted to visual areas supporting object perception is unclear. We show that a subcortical area, the pulvinar in the thalamus, helps sustain activity in the cortex and regulates the information transmitted between the fronto-parietal attention network and visual cortex. This suggests that the thalamus, classically considered as a simple relay for sensory information, contributes to higher-level cognitive functions.

Objectives Deep brain stimulation (DBS) of the ventral intermediate (Vim) thalamic nucleus is used to treat tremors. Here, we identified the Vim nucleus on fast gray matter acquisition T1 inversion recovery (FGATIR) images and delineated the dentate-rubrothalamic tract (DRT) to determine the DBS target. We evaluated whether this method could consistently identify the Vim nucleus by anatomical imaging and fiber tractography. Methods We retrospectively reviewed clinical data of patients who underwent unilateral thalamic DBS for severe tremor disorders. We evaluated outcomes at baseline, 6 months and 1 year following intervention, and annually thereafter. We reviewed preoperative planning to determine whether our tractography technique could consistently depict the DRT, and evaluated implanted electrode position by fusing postoperative CT scans to preoperative MR images. Results Seven patients (three men and four women) were included; preoperative diagnoses included essential tremor (n = 3), Parkinson's (n = 2), and Holmes tremor (n = 2). All patients responded to DBS therapy; motor scores improved at 6-month and last follow-up. The Vim nucleus was successfully identified, as the DRT was depicted in all cases. Of ten active DBS contacts in seven leads, four contacts were located outside of the depicted DRT, and these contacts tended to require higher stimulation intensity. Conclusions The Vim nucleus was successfully identified with FGATIR. Our methods may be useful to determine optimal DBS trajectory, and potentially improve outcomes.

The mammalian visual system is one of the most well-studied brain systems. Visual information from the retina is relayed to the dorsal lateral geniculate nucleus of the thalamus (LGd). The LGd then projects topographically to primary visual cortex (VISp) to mediate visual perception. In this view, the VISp is a critical network hub where visual information must traverse LGd-VISp circuits to reach higher-order ‘extrastriate’ visual cortices, which surround the VISp on its medial and lateral borders. However, decades of conflicting reports in a variety of mammals support or refute the existence of extrastriate LGd connections that can bypass the VISp. Here, we provide evidence of bidirectional extrastriate connectivity with the mouse LGd. Using small, discrete coinjections of anterograde and retrograde tracers within the thalamus and cortex, our cross-validated approach identified bidirectional thalamocortical connectivity between LGd and extrastriate visual cortices. We find robust reciprocal connectivity of the medial extrastriate regions with LGd neurons distributed along the ‘ventral strip’ border with the intergeniculate leaflet. In contrast, LGd input to lateral extrastriate regions is sparse, but lateral extrastriate regions return stronger descending projections to localized LGd areas. We show further evidence that axons from lateral extrastriate regions can overlap onto medial extrastriate-projecting LGd neurons in the ventral strip, providing a putative subcortical LGd pathway for communication between medial and lateral extrastriate regions. Overall, our findings support the existence of extrastriate LGd circuits and provide novel understanding of LGd organization in rodent visual system.

The pulvinar of the thalamus is a higher-order thalamic nucleus that is responsible for gating information flow to the cortical regions of the brain. It is involved in several cortico-thalamocortical relay circuits and is known to be affected in a number of neurological disorders. Segmenting the pulvinar in clinically acquired images is important to support studies exploring its role in brain function. In recent years, we have proposed an active shape model method to segment multiple thalamic nuclei, including the pulvinar. The model was created by manual delineation of high resolution 7T images and the process was guided by the Morel stereotactic atlas. However, this model is based on a small library of healthy subjects, and it is important to validate the reliability of the segmentation method on a larger population of clinically acquired images. The pulvinar is known to have particularly strong white matter connections to the hippocampus, which allows us to identify the pulvinar from thalamic regions of high hippocampal structural connectivity. In this study, we obtained T1-weighted and diffusion MR data from 43 healthy volunteers using a clinical 3T MRI scanner. We applied the segmentation method to the T1-weighted images to obtain the intrathalamic nuclei, and we calculated the connectivity maps between the hippocampus and thalamus using the diffusion images. Our results show that the shape model segmentation consistently localizes the pulvinar in the region with the highest hippocampal connectivity. The proposed method can be extended to other nuclei to further validate our segmentation method.

The thalamus receives input from 3 distinct cortical layers, but input from only 2 of these has been well characterized. We therefore investigated whether the third input, derived from layer 6b, is more similar to the projections from layer 6a or layer 5. We studied the projections of a restricted population of deep layer 6 cells (“layer 6b cells”) taking advantage of the transgenic mouse Tg(Drd1a-cre)FK164Gsat/Mmucd (Drd1a-Cre), that selectively expresses Cre-recombinase in a subpopulation of layer 6b neurons across the entire cortical mantle. At P8, 18% of layer 6b neurons are labeled with Drd1a-Cre::tdTomato in somatosensory cortex (SS), and some co-express known layer 6b markers. Using Cre-dependent viral tracing, we identified topographical projections to higher order thalamic nuclei. VGluT1+ synapses formed by labeled layer 6b projections were found in posterior thalamic nucleus (Po) but not in the (pre)thalamic reticular nucleus (TRN). The lack of TRN collaterals was confirmed with single-cell tracing from SS. Transmission electron microscopy comparison of terminal varicosities from layer 5 and layer 6b axons in Po showed that L6b varicosities are markedly smaller and simpler than the majority from L5. Our results suggest that L6b projections to the thalamus are distinct from both L5 and L6a projections, Z.M.’s laboratory is supported by Medical Research Council (G00900901), Biotechnology and Biological Sciences Research Council (BB/1021833) and The Wellcome Trust (092071/Z/10/Z). E.G. held an MRC Doctoral Studentship; S.H. is supported from Daiichi Sankyo Foundation of Life Science, Japan, L.U. is supported by OXION Wellcome Trust Initiative, Oxford. Y.K. is supported from the Pennsylvania Department of Health using Tobacco CURE Funds SAP#4100062216; P.K. from National Institutes of Health (NIH) R01DC009607 and a visiting Fellowship at St. Catherine’s College, Oxford. F.C.’s laboratory is supported by Human Brain Project (European Flagship, Ref. GA 604102 and Ministerio de Economia y Competitividad MINECO (Spain; Grant BFU2017-88549-P))

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions.SIGNIFICANCE STATEMENTIn the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning.

The thalamic reticular nucleus (TRN) is a thin layer of GABAergic cells lying rostral and lateral to the dorsal thalamus, and its projection to thalamic relay cells (i.e., the reticulothalamic pathway) strongly inhibits these cells. In an attempt to extend earlier studies of reticulothalamic connections to sensory thalamic nuclei, we used laser-scanning photostimulation to study the reticulothalamic projections to the main motor thalamic relays, the ventral anterior and lateral (VA and VL) nuclei, as well as to the nearby central lateral (CL) thalamic nucleus. VA/VL and the earlier studied somatosensory thalamic nuclei are considered “core” nuclei with topographic thalamocortical projections, whereas CL is thought to be a “matrix” nucleus with diffuse thalamocortical projections. We found that the TRN input footprints to VA/VL and CL are spatially localized and topographic and generally conform to the patterns established earlier for the TRN projections to sensory thalamic relays. These remarkable similarities suggest similar organization of reticulothalamic pathways and TRN regulation of thalamocortical communication for motor and sensory systems and perhaps also for core and matrix thalamus. Furthermore, we found that VA/VL and CL shared overlapping TRN input regions, suggesting that CL may also be involved in the relay of motor information.

Introduction: A typical absence epilepsy is a type of nonconvulsive and generalized epilepsy. The main feature of these attacks is a sudden brief impairment of consciousness. The disturbances in thalamocortical loop play an important role in pathogenesis of absence seizures. However, it is not clear that which part of this network triggers the seizure. This study was aimed to investigate the role of latrodorsal (LD) thalamic neurons during spike and wave discharges (SWDs) in WAG/Rij rats, as the most valid animal model of absence epilepsy. Materials and Methods: Single unit activities in the LD thalamic nucleus and electrocorticogram of somatosensory cortex were simultaneously recorded in six-month-old WAG/Rij rats. Results: During SWDs, unit activity in the LD thalamic nucleus showed burstlike discharges, which were started before the peak component of SWDs. In SWD-free periods, burst like activity in the LD was reduced. Conclusion: Our findings suggest that the burst firing of LD may stimulate the neocortex to exhibit SWDs. It can be concluded that inhibition of

Question The centro-median thalamic nucleus (Ce) must be correctly identified for deep brain stimulation (DBS). We have analysed the properties of Ce and surrounding nuclei in anaesthetized humans. Methods We recorded with microelectrodes in 6 patients bilaterally operated for intractable epilepsy, starting 10 mm from the target (coordinates x = 8, y = −10, z = 0 mm). The ventro-caudal thalamic nucleus (V.c.) is defined by the presence of somato-sensory evoked potentials recorded through microelectrodes (SSEPm). Then, the real trajectory through the thalamus is reconstructed considering the depth where SSEPm were obtained. We have analysed these properties: density (number of units), amplitude (μV), duration at the half amplitude (μs), maximum and minimum value of first derivative (Dmax/Dmin, V/s) and frequency (Hz) from fasciculoso medial/lamina medialis (Mf) c/lm, Zentro-oralis (Z.o.e/Z.o.i), Ventral oralis posterior (V.o.p), V.c, Ventralis intermedius (V.im.i), Ce magnocelullar (Ce.mc) and parvocellular (Ce.pc). Results SSEPm (see below for its definition) were obtained only in 4 trajectories from 3 patients, from which we have obtained all the results. The properties of spikes from different nuclei are shown in the next table. In relation to SSEP, we have obtained two kind of responses: i) low amplitude ( 1300 Hz, termed HFO) and ii) High Amplitude (>25 μV) and lowest frequency ( Conclusions (1) It’s easy differentiate between cells from Ce and the other surrounding thalamic nuclei by the properties of its action potentials. (2) However, it’s not so easy to discriminate the Ce.mc and Ce.pc. (3) SSEPm (HAO) are extremely valuable in the identification of the somato-sensory part of thalamus. (4) However, they are very restricted spatially and not always can be recorded during the trajectory. (5) SSEPm must be differentiated from HFO which are broader represented in several nuclei, unlike than V.c.

Background: The thalamic nucleus ventralis intermedius (Vim nucleus) is the main surgical target for the management of intractable tremor. The Vim nucleus cannot be reliably located with routine stereotactic imaging, and so targeting relies on indirect coordinates. Objective: We propose to investigate if colored fractional anisotropy (FA) mapping can help to locate the Vim nucleus by identifying its borders, particularly the prelemniscal radiations (Raprl) that lie below and behind the nucleus. Method: We retrospectively reviewed the colored FA maps for 18 consecutive patients having undergone gamma knife stereotactic Vim thalamotomy for disabling tremor. Results: The Raprl were easily located on colored FA maps and enabled the identification of the lower and posterior borders of the Vim nucleus in all patients. In the medial plane, the mean distance ± SD between the Raprl and Vim nucleus was 0.77 ± 1.19 mm (range: 0.1-3.3). The Raprl were located 1.35 ± 1.33 mm (range: 0.2-3.9) behind the Vim nucleus and 1.99 ± 1.23 mm (range: 0.7-4.4) below it. The mean vector distance ± SD between the Vim nucleus and the Raprl was 3 ± 1.38 mm (range: 1.25-5.2). Conclusion: The Raprl can be easily seen on colored FA maps and constitute a reliable landmark for the borders of the Vim nucleus.

Background: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. Methods: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. Results: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. Conclusion: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.

The rodent orbitofrontal cortex is involved in a variety of cognitive and behavioral functions that require thalamic input to be successfully expressed. Although the thalamic nucleus submedius (Sm) is a major source of afferents to the orbitofrontal cortex, thalamocortical projection from the Sm has not been fully elucidated. In the present study, we first divided the rat Sm into dorsal and ventral parts according to the distribution of vesicular glutamate transporter 2-immunoreactive varicosities, which were somatosensory afferents from the brain stem. Subsequently we investigated dendritic and axonal arborizations of individual dorsal and ventral Sm neurons by visualizing the processes with Sindbis virus vectors expressing membrane-targeted fluorescent proteins. The number of dendritic processes of ventral Sm neurons was greater than that of dorsal Sm neurons. In the cerebral cortex, all the reconstructed Sm neurons sent axons primarily to layers 2-5. Interestingly, dorsal Sm neurons formed a single axon arbor exclusively within the ventrolateral orbital area, whereas ventral Sm neurons made two axon arbors in the lateral orbital and ventral orbital areas simultaneously. The spread of each axon arbor was 500-1000 µm in diameter in the direction tangential to the cortical surface. These results indicate that the dorsal and ventral Sm comprise two distinct thalamocortical pathways. The dorsal Sm pathway relay somatosensory information to the ventrolateral orbital area and may be involved in emotional and aversive aspects of nociceptive information processing, whereas the ventral Sm pathway seems to co-activate distant orbitofrontal cortical areas, and may link their functions under certain circumstances. This article is protected by copyright. All rights reserved.

Commentary on : Elias WJ, Lipsman N, Ondo WG, et al. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med 2016;375:730–9.[OpenUrl][1][PubMed][2] Propranolol and primidone significantly reduce tremor by around 60% in 50% of patients with essential tremor (ET). When medication is ineffective or causes intolerable side effects, neurosurgical intervention may be considered. Until recently, radiofrequency (RF) ablation or deep brain stimulation (DBS) of the ventralis intermedius (VIM) thalamic nucleus were the main surgical options. Gamma knife thalamotomy avoids a burrhole but delayed effects make intraoperative validation impossible.1 Recent technical advances have enabled transcranial delivery of high-intensity focused ultrasound to create a thalamotomy with MRI guidance and … [1]: {openurl}?query=rft.jtitle%253DN%2BEngl%2BJ%2BMed%26rft.volume%253D375%26rft.spage%253D730%26rft_id%253Dinfo%253Apmid%252F27557301%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=27557301&link_type=MED&atom=%2Febmed%2F22%2F2%2F64.atom

Background Parkinsonian rigidity is alleviated by thalamotomy targeting the thalamic nucleus ventralis lateralis. Detecting there the exaggerated 13–27-Hz β-band activities, we hypothesized that these activities centrally drove rigidity. Aim To test this hypothesis, we examined the temporal relationships of rigidity with β-band activities. Methods In 20 patients with Parkinson's disease, we monitored the thalamic local field potentials and multiple unit spikes with the electromyograms of neck and limb muscles. Results The resting state of muscles with exaggerated tonic discharges in electromyograms was regarded to represent rigidity. The compound muscle spikes as such were accompanied by or synchronized with the thalamic β-band activities when the thalamic recording sites somatotopically met the muscles of interest. The β-band activities consisted of the negative-going deflection of local field potentials and negativity-dominant multiple unit spikes. The β-band local field potentials led to the muscle spikes in spontaneous initiation and development of rigidity, as well as in the cyclic sequence of β-band activities and electromyograms. The paired β-band local field potentials and muscle spikes were moderately correlated in amplitude. During the observation, the grade of rigidity spontaneously fluctuated. Accordingly, the phase coincidence of β-band local field potentials and muscle spikes occurred contingently. When the β-band and tremor-locked 3–7-Hz τ-range activities coexisted at the recording site, different groups of thalamic neurons led to rigidity and tremor, respectively, as their peripheral outcomes. Conclusion The results suggest that the thalamic β-band hyperactivities contingently drive rigidity in support for the central origin hypothesis of rigidity.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked adult-onset neurodegenerative disorder that affects carriers of the fragile X mental retardation 1 ( FMR1 ) gene premutation, which is a 55–200 CGG repeat expansion in the 5ʹ untranslated region of the gene.1 The core symptoms of FXTAS are progressive intention tremor and cerebellar ataxia. These symptoms can be disabling and, when combined, severely reduce the patient's quality of life. Symptomatic control with medication has limited effects.1 Very few cases have been treated with deep brain stimulation (DBS), mostly in the ventrointermediate thalamic (VIM) nucleus. This treatment results in tremor improvement with either no benefit or worsening of the ataxia and balance.2–4 We present a patient who experienced long-term tremor control and ataxia improvement after chronic bilateral stimulation of the ventro-oralis posterior thalamic nucleus and zona incerta (VoP/ZI), which resulted in significant improvement in daily life activities.

Two main neuronal pathways connect facial whiskers to the somatosensory cortex in rodents: (i) the lemniscal pathway, which originates in the brainstem principal trigeminal nucleus and is relayed in the ventroposterior thalamic nucleus and (ii) the paralemniscal pathway, originating in the spinal trigeminal nucleus and relayed in the posterior thalamic nucleus. While lemniscal neurons are readily activated by whisker contacts, the contribution of paralemniscal neurons to perception is less clear. Here, we functionally investigated these pathways by manipulating input from the whisker pad in freely moving mice. We report that while lemniscal neurons readily respond to neonatal infraorbital nerve sectioning or whisker contacts in vivo, paralemniscal neurons do not detectably respond to these environmental changes. However, the paralemniscal pathway is specifically activated upon noxious stimulation of the whisker pad. These findings reveal a nociceptive function for paralemniscal neurons in vivo that may critically inform context-specific behaviour during environmental exploration.

Object This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads. Methods Eighteen heads of fresh human cadavers were removed with a dedicated protocol preventing intracerebral air penetration. The MR images allowed determination of the ultrasonic target: a part of the thalamic nucleus ventralis intermedius implicated in essential tremor. Osseous aberrations were corrected with simulation-based time reversal by using CT data from the heads. The ultrasonic session was performed with a 512-element phased-array transducer system operating at 1 MHz under stereotactic conditions with thermometric real-time MR monitoring performed using a 1.5-T imager. Results Dissection, imaging, targeting, and planning have validated the feasibility of this human cadaver model. The average temperature elevation measured by proton resonance frequency shift was 7.9°C ± 3°C. Based on MRI data, the accuracy of MRgHIFU is 0.4 ± 1 mm along the right/left axis, 0.7 ± 1.2 mm along the dorsal/ventral axis, and 0.5 ± 2.4 mm in the rostral/caudal axis. Conclusions Despite its limits (temperature, vascularization), the human cadaver model is effective for studying the accuracy of MRgHIFU brain therapy. With the 1-MHz system investigated here, there is millimetric accuracy.

The ventro-intermediate nucleus (Vim), as the others thalamic subparts, cannot be directly visualized by current standard magnetic resonance imaging (MRI), in daily clinical practice. Hence, for treatment of tremor in functional neurosurgery, where the commonly used target is the Vim, the targeting procedure is done indirectly. We present a novel direct automated segmentation of the Vim using only subject-related MRI information, specifically, diffusion MRI at 3T and susceptibility weighted images (SWI) acquired at 7T. With a state-of-the-art method based on local diffusion MR properties for automated subdivision of the thalamus, we first restrain the region of interest to the group of motor-related nuclei. Then, this thalamic part is further subdivided, in graph parcellation manner, using the intensity-related features provided by SWI together with prior knowledge of the Vim localization inside the motor thalamic segment. Our framework was tested in four healthy elderly subjects, for eight thalami in total, and the results were evaluated by an experienced neurosurgeon, showing the ability to directly detect the Vim area. The qualitative inspection indicated that the proposed method outperforms standard multi-atlas based techniques.