Anterior Thalamic Nuclei Research Articles

The anterior and medial thalamic nuclei and the human limbic system: tracing the structural connectivity using diffusion-weighted imaging

The limbic system is a phylogenetically old, behaviorally defined system that serves as a center for emotions. It controls the expression of anger, fear, and joy and also influences sexual behavior, vegetative functions, and memory. The system comprises a collection of tel-, di-, and mesencephalic structures whose components have evolved and increased over time. Previous animal research indicates that the anterior nuclear group of the thalamus (ANT), as well as the habenula (Hb) and the adjacent mediodorsal nucleus (MD) each play a vital role in the limbic circuitry. Accordingly, diffusion imaging data of 730 subjects obtained from the Human Connectome Project and the masks of six nuclei (anterodorsal, anteromedial, anteroventral, lateral dorsal, Hb, and MD) served as seed regions for a direct probabilistic tracking to the rest of the brain using diffusion-weighted imaging. The results revealed that the ANT nuclei are part of the limbic and the memory system as they mainly connect via the mammillary tract, mammillary body, anterior commissure, fornix, and retrosplenial cortices to the hippocampus, amygdala, medio-temporal, orbito-frontal and occipital cortices. Furthermore, the ANT nuclei showed connections to the mesencephalon and brainstem to varying extents, a pattern rarely described in experimental findings. The habenula—usually defined as part of the epithalamus—was closely connected to the tectum opticum and seems to serve as a neuroanatomical hub between the visual and the limbic system, brainstem, and cerebellum. Finally, in contrast to experimental findings with tracer studies, directly determined connections of MD were mainly confined to the brainstem, while indirect MD fibers form a broad pathway connecting the hippocampus and medio-temporal areas with the mediofrontal cortex.

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus

ObjectiveThe goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability). MethodsFive patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT. We analyzed the extent of gamma-band response (activation or suppression) and post-stimulation change in excitability in various cortical regions during low (10 Hz) and high (50 Hz) frequency stimulations. Results10 Hz stimulation increased cortical gamma, whereas 50 Hz stimulation suppressed the gamma responses. The maximum response to stimuli was in the hippocampus. High epileptogenicity regions were more susceptible to stimulation. Both 10-and 50 Hz stimulations decreased post-stimulation cortical excitability. The greater the gamma-band activation with 10 Hz stimulation, the greater was the decrease in post-stimulation excitability. ConclusionsWe define an EEG marker that delineates stimulation-specific nodal engagement. We proved that nodes that were engaged with the thalamus during stimulation were more likely to show a short term decrease in post-stimulation excitability. SignificancePatient-specific engagement patterns during stimulation can be mapped with SEEG that can be used to optimize stimulation parameters.

Anterior thalamic nucleus deep brain stimulation for refractory epilepsy: Preliminary results in our first 5 patients

ObjectivesDeep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) has been recognized to be an efficient treatment of refractory epilepsy (RE). However, ATN targeting is difficult and up to 8% of lead misplacement is reported. Our objective is to report our surgical procedure based on MRI targeting and our clinical results. Patients and methodsOur first five consecutive patients (4M, 1F, mean age: 42.8 years) treated by DBS of ATN between March and October 2016 were included. The mean duration of their epilepsy was 29 years. Four patients had already vagal nerve stimulation and 2 mammillary body stimulation. Stereotactic coordinates were calculated using distal segment of mammillothalamic tract as landmark. All procedures were performed under general anesthesia with intraoperative control of lead position using a robotic 3D fluoroscopy and image fusion with the preoperative MRI. ResultsNo complications or lead misplacement was observed. The mean 3D distance between the planned target and location of the lead was 1.8 mm. Each patient was followed up at least one year (15+3months). The stimulation parameters were: 140Hz, 90m/s and 5 Volts with one minute ON/five minutes OFF cycle. The mean reduction of seizure frequency reached −52.5% (+32.2) at 6-months but decreased to −24.5% (+65.7) at the last follow-up due to some adverse events not related to stimulation. ConclusionNo complication, no lead misplacement and the improvement in our first patients, previously not help by multiple medications or surgeries, are encouraging.

A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation

As we navigate in space, external landmarks and internal information guide our movement. Circuit and synaptic mechanisms that integrate these cues with head-direction (HD) signals remain, however, unclear. We identify an excitatory synaptic projection from the presubiculum (PreS) and the multisensory-associative retrosplenial cortex (RSC) to the anterodorsal thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. Invitro, projections to TRN involve AMPA/NMDA-type glutamate receptors that initiate TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei. Invivo, chemogenetic anterodorsal TRN inhibition modulates PreS/RSC-induced anterior thalamic firing dynamics, broadens the tuning of thalamic HD cells, and leads to preferential use of allo- over egocentric search strategies in the Morris water maze. TRN-dependent thalamic inhibition is thus an integral part of limbic navigational circuits wherein it coordinates external sensory and internal HD signals to regulate the choice of search strategies during spatial navigation.

Two Thalamic Regions Screened Using Laser Capture Microdissection with Whole Human Genome Microarray in Schizophrenia Postmortem Samples.

We used whole human genome microarray screening of highly enriched neuronal populations from two thalamic regions in postmortem samples from subjects with schizophrenia and controls to identify brain region-specific gene expression changes and possible transcriptional targets. The thalamic anterior nucleus is reciprocally connected to anterior cingulate, a schizophrenia-affected cortical region, and is also thought to be schizophrenia affected; the other thalamic region is not. Using two regions in the same subject to identify disease-relevant gene expression differences was novel and reduced intersubject heterogeneity of findings. We found gene expression differences related to miRNA-137 and other SZ-associated microRNAs, ELAVL1, BDNF, DISC-1, MECP2 and YWHAG associated findings, synapses, and receptors. Manual curation of our data may support transcription repression.

Desynchronization of temporal lobe theta-band activity during effective anterior thalamus deep brain stimulation in epilepsy

BackgroundBilateral cyclic high frequency deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) reduces the seizure count in a subset of patients with epilepsy. Detecting stimulation-induced alterations of pathological brain networks may help to unravel the underlying physiological mechanisms related to effective stimulation delivery and optimize target engagement. MethodsWe acquired 64-channel electroencephalography during ten ANT-DBS cycles (145 ​Hz, 90 ​μs, 3–5 ​V) of 1-min ON followed by 5-min OFF stimulation to detect changes in cortical activity related to seizure reduction. The study included 14 subjects (three responders, four non-responders, and seven healthy controls). Mixed-model ANOVA tests were used to compare differences in cortical activity between subgroups both ON and OFF stimulation, while investigating frequency-specific effects for the seizure onset zones. ResultsANT-DBS had a widespread desynchronization effect on cortical theta and alpha band activity in responders, but not in non-responders. Time domain analysis showed that the stimulation induced reduction in theta-band activity was temporally linked to the stimulation period. Moreover, stimulation induced theta-band desynchronization in the temporal lobe channels correlated significantly with the therapeutic response. Responders to ANT-DBS and healthy-controls had an overall lower level of theta-band activity compared to non-responders. ConclusionThis study demonstrated that temporal lobe channel theta-band desynchronization may be a predictive physiological hallmark of therapeutic response to ANT-DBS and may be used to improve the functional precision of this intervention by verifying implantation sites, calibrating stimulation contacts, and possibly identifying treatment responders prior to implantation.

High-frequency electrical stimulation of the anterior thalamic nuclei increases vigilance in epilepsy patients during relaxed and drowsy wakefulness.

High-frequency deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduces the frequency and intensity of focal and focal to bilateral tonic-clonic epileptic seizures. We investigated the impact of high-frequency ANT-DBS on vigilance in epilepsy patients during relaxed and drowsy wakefulness, to better understand the effects and the mechanisms of action of this intervention in humans. Four patients with different structural epileptic pathologies were included in this retrospective case-cohort study. Short- and long-term electroencephalography (EEG) was used to determine states of relaxed or drowsy wakefulness and the vigilance changes during stimulation-on and stimulation-off intervals. In relaxed, wakeful patients with eyes closed, the eyelid artifact rate increased acutely and reproducibly during stimulation-on intervals, suggesting an enhanced vigilance. This effect was accompanied by a slight acceleration of the alpha rhythm. In drowsy patients with eyes closed, stimulation generated acutely and reproducibly alpha rhythms, similar to the paradoxical alpha activation during eyes opening. The occurrence of the alpha rhythms reflected an increase in the vigilance of the drowsy subjects during ANT-DBS. This is the first demonstration that ANT-DBS increases the vigilance of wakeful epilepsy patients. Our results deliver circumstantial evidence that high-frequency ANT-DBS activates thalamocortical connections that promote wakefulness.

Defining the optimal target for anterior thalamic deep brain stimulation in patients with drug-refractory epilepsy.

The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS. From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space. Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up. Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

The mammillothalamic tracts: Age-related conspicuity and normative morphometry on brain magnetic resonance imaging.

The mammillothalamic tract (MTT, bundle of Vicq d'Azyr) is a white-matter projection from each mammillary body to the anterior nucleus of the thalamus (ANT). Deep brain stimulation of the MTTs or ANTs is a treatment option for medically refractory focal epilepsy. Since the ANTs may be atrophied in epilepsy, targeting of the MTT terminations could be used as a proxy for ANT locations. However, MTT conspicuity and morphometry on MRI have not been evaluated to date. We investigated normative age- and sex-related MRI morphometrics of the MTTs in healthy individuals. We retrospectively analyzed magnified axial T2-weighted images of 80 subjects for bilateral MTT conspicuity, diameters, areas, shapes, precise locations, and symmetry. We statistically tested the effects of independent variables (sex and MTT side) on measured dependent variables using two-way ANOVA; and performed linear regressions with age as the independent variable for each of the dependent variables. Subjects were F:M = 44:36, with mean age 45.3 years. Only one (0.63%) MTT was inconspicuous. Mean MTT diameter was 1.8 mm, area was 2.0 mm2 , and distance from third ventricle was 3.1 mm. MTTs were mostly bilaterally symmetrical in shape, equally round, or ovoid. The right MTT diameter was larger than the left, and males had larger MTT areas than females. We found no statistical difference between MTT diameters and areas in young, middle-aged, and older adults. We report normative axial MRI morphometrics of the MTTs to guide neuromodulation treatments. Future detailed analyses will determine if the MTTs atrophy in proportion to the ANTs in refractory epilepsy.

Variability Between Direct and Indirect Targeting of the Anterior Nucleus of the Thalamus

Preoperative thalamic targeting methods have historically relied on indirect targeting techniques that do not fully account for variances in anatomy or for thalamic atrophy in epilepsy. We aimed to address variability noted between traditional indirect targeting and direct targeting methods for the anterior nucleus of the thalamus (ANT). Fifteen consecutive patients undergoing ANT deep brain stimulator placement were evaluated (30 thalamic nuclei). Direct ANT targeting was performed using a fast gray matter acquisition T1 inversion recovery sequence and compared with standard stereotactic coordinates. Thalamic volumes were calculated for each patient, and degree of thalamic volume loss was assessed compared with matched control subjects. Vertex analysis was performed to assess shape changes in the thalamus compared with age- and sex-matched subjects. There was significant variation between direct and indirect targets in the y-axis and z-axis on both sides. On the left, the direct target was located at y= 2 ±1.3 mm and z= 9.3 ± 1.8 mm (both P= 0.02). On the right, the direct target was located at y= 2.9 ± 1.8 mm and z= 9.2 ± 2 mm (both P ≤ 0.0003). There was no significant difference in the x-coordinate on either side (P > 0.5). Additionally, there was a correlation between thalamic volume and difference between direct and indirect targets in the y-axis and the z-axis. We showed a significant difference in direct and indirect targeting in the y-axis and z-axis when targeting the ANT for deep brain stimulation for epilepsy. This difference is correlated to thalamic volume, with a larger difference noted in patients with thalamic atrophy.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Direct visual targeting versus preset coordinates for ANT-DBS in epilepsy.

Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) may be used against refractory focal epilepsy, but only two randomized double-blinded trials have been performed. The Oslo study was discontinued prematurely since reduction in seizure frequency was less than expected. The aim of the present study was to review the targeting used in the Oslo study and to identify the actual positions of the contacts used for stimulation. BrainLab MRI data were available from 12 Oslo study patients. Based on MRI the coordinates of the center of the ANT were identified. The coordinates were considered as the visually identified preferred target and were compared with the target originally used for ANT electrode implantation and with the actual electrode positions estimated from post-operative CT scans. We found considerable differences between the visually identified preferred target, the originally planned target, and the actual electrode position. The total distance between the active electrode position and the visually identified preferred target was on average 3.3mm on the right and 2.9mm on the left side. Indirect targeting based on preset coordinates may contribute to explain the modest effect of ANT-DBS on seizure frequency seen in the Oslo study. Observed differences between the center of the ANT and the actual electrode position may at least in part be explained by variations in position and size of the ANT. Direct identification of the target using better MRI imaging protocols is recommended for future ANT-DBS surgery.

Functional Activation Patterns of Deep Brain Stimulation of the Anterior Nucleus of the Thalamus

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of invivo biomarkers. We propose a method for investigating the invivo stimulation effects using blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) and present the brain activation pattern associated with ANT DBS. Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30-second blocks. The scanner was triggered using surface electrophysiologic recordings to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. Using block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown, suggesting that these nodes may modulate the effect of seizure control with ANT DBS.

Frameless Deep Brain Stimulation Surgery: A Single-Center Experience and Retrospective Analysis of Placement Accuracy of 220 Electrodes in a Series of 110 Patients

Background: Proper lead placement is considered one of the key factors in achieving a good clinical outcome in deep brain stimulation (DBS), but there is still considerable controversy surrounding the accuracy of the frameless in comparison to the frame-based technique. Objective: We report our single-center experience with DBS electrode placement to evaluate the accuracy of the frameless stereotactic system. Methods: We prospectively analyzed the data of 110 patients who underwent DBS surgery for Parkinson disease, dystonia, essential tremor, or refractory epilepsy. The final targets (FTs) of the 220 leads were: subthalamic nucleus, globus pallidus pars interna, ventralis intermedius nucleus, and anterior nuclei of thalamus in thalamus. A bilateral stereotactic approach using a combined identification of target based on preoperative images (MRI and CT scan fusion) and intra-operative micro-electrode recording (MER) were done. We collected and compared the coordinates of planned target (PT), the definitive expected target (ET) during MER, and the effective final location (FT) of the lead using the postoperative CT. Accuracy was assessed by both vector error (VE) and deviation from the PT. Results: The mean and SD from PTs was 0.78 ± 0.43 mm in the x direction, 0.68 ± 0.41 mm in the y direction, and 0.76 ± 0.41 mm in the z direction. Global VE was 1.43 ± 0.37. Conclusion: Frameless systems appear to be a reliable and accurate technique.

Spatial Coding in the Subiculum Requires Anterior Thalamic Inputs

Hippocampal function relies on the anterior thalamic nuclei, yet the reasons remain poorly understood. While anterior thalamic lesions disrupt parahippocampal spatial signalling, their impact on the subiculum is unknown, despite the importance of this area for hippocampal networks. We recorded subiculum cells in rats with either permanent (N-methyl-D-aspartic acid) or reversible (muscimol) anterior thalamic lesions. The diverse spatial signals normally found in the subiculum, including place cells, disappeared following permanent thalamic lesions and showed marked disruption during transient lesions. Meanwhile, permanent anterior thalamic lesions had no discernible impact on CA1 place fields. Thalamic lesions reduced spatial alternation performance (permanently or reversibly) to chance levels, while leaving a non-spatial recognition memory task unaffected. These findings, which help to explain why anterior thalamic damage is so deleterious for spatial memory, cast a new spotlight on the importance of subiculum function, and reveal its dependence on anterior thalamic signalling.

Organisation of cingulum bundle fibres connecting the anterior thalamic nuclei with the rodent anterior cingulate and retrosplenial cortices

Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length.

Probing circuit of Papez with stimulation of anterior nucleus of the thalamus and hippocampal evoked potentials

PurposeDespite documented clinical effectiveness, deep brain stimulation (DBS) therapy for drug-resistant epilepsy rarely yields long-term seizure free outcomes. MethodsThis pilot study in five patients investigated circuit of Papez evoked potentials (EPs) using hippocampal sensing during anterior nucleus of the thalamus (ANT) electrical stimulation. We hypothesize that hippocampal EP is a potential biomarker that could be useful for ANT electrode targeting and improving seizure reduction. We obtained bilateral circuit of Papez EPs in five patients with bilateral temporal lobe epilepsy (TLE). The circuit of Papez EPs were measured and assessed by signal amplitude. Volumetric analysis of relevant mesial temporal structures and ANT stimulation analysis was performed on immediate post-implantation images. ResultsThe patient with the most favorable seizure outcome, which meant long-term seizure reduction greater than 50 % compared to baseline, had strong bilateral EPs and normal hippocampal structure. Conversely, those without clinical benefit with ANT DBS had absent or weak bilateral EPs as well as MRI findings consistent with mesial temporal sclerosis (MTS). ConclusionThe data support the hypothesis that hippocampal EPs with ANT stimulation may be used to as a surrogate marker to probe circuit of Papez and predict ANT DBS efficacy.

Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) has been shown to be effective and safe in the long-term treatment of refractory epilepsy. However, the mechanisms by which ANT-DBS controls epilepsy at the gene expression level (e.g., which regulatory mechanisms are altered) is not well understood. Nine rats were randomly assigned to the control group, the kainic acid (KA) group, and the DBS group. Temporal lobe epilepsy in rats was induced by a stereotaxic KA injection (KA group). The DBS group received the KA injection followed by treatment with ANT-DBS. Video-electroencephalogram (EEG) was used to monitor seizures. Total RNA samples were isolated from the hippocampus of three groups. Microarray was used to detect differentially regulated mRNAs. GO and pathway analysis were performed to analyze the functional categories and affected pathways. qPCR was used to prove the reliability of the microarray results. The differentially expressed genes the KA group and the DBS group, relative to the control group, were screened and a total of 2910 genes were identified. These genes were involved in functional categories such as ion channel activity (P = 5.01 × 10-8), gated channel activity (P = 1.42 × 10-7), lipid binding (P = 4.97 × 10-5), and hydrolase activity (P = 5.02 × 10-5) and pathways such as calcium signaling pathway (P = 2.09 × 10-8), glutamatergic synapse (P = 4.09 × 10-8) and NOD-like receptor signaling pathway (P = 2.70 × 10-6). Differentially expressed mRNAs might play a role in the pathogenesis of temporal lobe epilepsy. Calcium signaling pathways, synaptic glutamate, and NOD-like receptor signaling pathway play a central role in normal-epilepsy-ANT-DBS treatment series. ANT-DBS achieves its antiepileptic effects by modulating target genes involved in a variety of functions and pathways.

Do the Dento-Thalamic Connections of Genetic Absence Epilepsy Rats from Strasbourg Differ from Those of Control Wistar Rats?

The thalamo-cortical circuit is important in the genesis of absence epilepsy. This circuit can be influenced by connecting pathways from various parts of central nervous system. The aim of the present study is to define the dento-thalamic connections in Wistar animals and compare the results with genetic absence epilepsy rats from Strasbourg (GAERS) using the biotinylated dextran amine (BDA) tracer. We injected BDA into the dentate nucleus of 13 (n = 6 Wistar and n = 7 GAERS) animals. The dento-thalamic connections in the Wistar animals were denser and were connected to a wider range of thalamic nuclei compared with GAERS. The dentate nucleus was bilaterally connected to the central (central medial [CM], paracentral [PC]), ventral (ventral medial [VM], ventral lateral [VL], and ventral posterior lateral [VPL]), and posterior (Po) thalamic nuclei in Wistar animals. The majority of these connections were dense contralaterally and scarce ipsilaterally. Contralateral connections were present with the parafascicular (PF), ventral posterior medial, ventral anterior (VA), and central lateral (CL) thalamic nuclei in Wistar animals. Whereas in GAERS, bilateral connections were observed with the VL and CM. Contralateral connections were present with the PC, VM, VA, and PF thalamic nuclei in GAERS. The CL, VPL, and Po thalamic nucleus connections were not observed in GAERS. The present study showed weak/deficit dento-thalamic connections in GAERS compared with control Wistar animals. The scarce information flow from the dentate nucleus to thalamus in GAERS may have a deficient modulatory role on the thalamus and thus may affect modulation of the thalamo-cortical circuit.

Susceptibility-Weighted Imaging Findings in Aspartylglucosaminuria.

Aspartylglucosaminuria is a rare lysosomal storage disorder that causes slowly progressive, childhood-onset intellectual disability and motor deterioration. Previous studies have shown, for example, hypointensity in the thalami in patients with aspartylglucosaminuria on T2WI, especially in the pulvinar nuclei. Susceptibility-weighted imaging is a neuroimaging technique that uses tissue magnetic susceptibility to generate contrast and is able to visualize iron and other mineral deposits in the brain. SWI findings in aspartylglucosaminuria have not been reported previously. Twenty-one patients with aspartylglucosaminuria (10 girls; 7.4-15.0 years of age) underwent 3T MR imaging. The protocol included an SWI sequence, and the images were visually evaluated. Thirteen patients (6 girls, 7.4-15.0 years of age) had good-quality SWI. Eight patients had motion artifacts and were excluded from the visual analysis. Thirteen healthy children (8 girls, 7.3-14.1 years of age) were imaged as controls. We found a considerably uniform distribution of decreased signal intensity in SWI in the thalamic nuclei in 13 patients with aspartylglucosaminuria. The most evident hypointensity was found in the pulvinar nuclei. Patchy hypointensities were also found especially in the medial and anterior thalamic nuclei. Moreover, some hypointensity was noted in globi pallidi and substantia nigra in older patients. The filtered-phase images indicated accumulation of paramagnetic compounds in these areas. No abnormal findings were seen in the SWI of the healthy controls. SWI indicates accumulation of paramagnetic compounds in the thalamic nuclei in patients with aspartylglucosaminuria. The finding may raise the suspicion of this rare disease in clinical practice.