Ventral Thalamic Nucleus Research Articles

Mechanisms of deep brain stimulation for essential tremor

Although essential tremor is often thought of as benign, it can be disabling to the point of justifying invasive deep brain stimulation (DBS). However, the mechanisms by which thalamic and subthalamic stimulation suppress tremor are poorly understood. In this issue of Brain , Groppa et al. (2014) quantified the performance of seven patients with essential tremor in a reaching task to determine the DBS target structures associated with therapeutic reduction in tremor and with the side effect of stimulation-induced ataxia. The optimum site of stimulation was usually in the posterior subthalamic area, beneath the inferior border of the thalamic nucleus ventralis intermedius. Probabilistic diffusion tractography identified the dentatothalamic tract as the key therapeutic DBS target structure. Supratherapeutic stimulation of this site produced upper limb ataxia, despite continued suppression of tremor. The authors systematically varied stimulation pulse strength and duration to find that stimulation chronaxies of 27 and 52 µs were associated with tremor suppression and the induction of ataxia, respectively. Chronaxie is loosely defined as the minimum duration at which a current twice threshold (minimum current with indefinitely long pulse duration) elicits a response and provides a clue as to the properties of the axons recruited. They reasoned that two different populations of large myelinated nerve fibres were affected: (i) dentatothalamic axons for the therapeutic effect; and (ii) afferent or efferent axons of the red nucleus for the stimulation-induced ataxia. However, the involvement of rubral pathways could not be confirmed with diffusion tractography. This work is an important contribution to a growing literature addressing the mechanisms of DBS and the preferred site of DBS stimulation for essential tremor. Ventralis intermedius has historically been the preferred stereotactic target for thalamotomy and DBS in the treatment of essential tremor and other tremor disorders (Miocinovic et al. , 2013), but recent postoperative correlations …

Fatal Familial Insomnia (FFI) Complicated by Posterior Reversible Encephalopathy Syndrome (PRES)

The descriptive term posterior reversible encephalopathy syndrome (pres) represents a clinical-radiological syndrome which appears mostly in the context of an acute increase in blood pressure or in connection with the taking of immunosuppressive medication. Clinically it is marked by headaches, impairment of consciousness, visual impairment, and epileptic seizures. radiologically can be proved symmetric most frequently parietooccipitale vasogenic edema [1], which are usually reversible within days till weeks. We report on a 44-year-old woman with fatal familial insomnia which has developed a pres syndrome within the framework of a hypertensive blood pressure with autonomous dysregulation. FFI is rare, rapidly progressive autosomal dominant inherited prion disease with typical clinical symptoms such as nocturnal ischemia daytime sleepiness, progressive dementia, hallucinations, autonomic disorder, endocrine manifestations, motoric disorder, and neuropathologic selective atrophy of anterior ventral and mediodorsal thalamic nuclei [2–5]. The differential diagnosis included initially a Creutzfeldt Jakob disease, an encephalopathy with Hashimoto thyreoiditis, CAdAsIL, Morbus Whipple, or a paraneoplastic encephalopathy. Interesting in this case is the manifestation of pres in a patient with FFI caused by the autonomic disorder.

The origin of projections from the posterior cingulate and retrosplenial cortices to the anterior, medial dorsal and laterodorsal thalamic nuclei of macaque monkeys

Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition.

Oscillatory activity in ventrolateral thalamus of patients with Parkinson's disease

Objective To explore the neuronal oscillatory activity in the ventrolateral thalamus (the ventral oral posterior nucleus,Vop/the ventral intermediate nucleus,Vim) in relation to parkinsonian motor signs.Methods 23 patients (M:20,F:3 ; mean age:60.6-± 8.2 years,mean duration of disease:6.6± 3.4 years) with Parkinson's disease (PD) who underwent thalamotomy were studied.Their mean Hoehn & Yahr score was 2.2 ± 0.4,and the unified Parkinson's disease rating scale (UPDRS Ⅲ)during OFFstate was 42.4 ± 12.1.The average L-dopa daily dose was 551.7 ± 219.5 mg.Microelectrode records in Vop/Vim and electromyography (EMG) on contralateral limbs to surgery were simultaneously performed.Single unit analysis,interspike interval (ISI) was used to study neuronal firing rate and pattern.Power spectral analysis was carried out to evaluate neuronal oscillation.Coherence analysis was used to study neuronal activity in relation to limb EMG.Clinical outcome was calculated by (presurgery-postsurgery/presurgery) × 100.Results 190 neurons were identified.Power spectral analysis showed that 60％ (n =114) neurons had oscillatory activity.Of those oscillatory neurons,78％ (n =89) neurons had tremor frequency band (3.0 ～ 7.5 Hz) (TFB).Oscillation showing as same frequency as tremor (P ＜0.05) ; 22％ (n =25) neurons had β frequency band(8 ～ 30 Hz) (βFB) oscillation.Further analysis showed that majority of neurons with TFB oscillation localized in Vim,while majority of neurons with βFB oscillations localized in Vop (t =2.048,P ＜ 0.05).In addition,it was found that the mean firing rate of oscillatory neurons in Vop was significantly lower than those neurons in Vim (24.3 ±9.9 Hz vs 28.5 ± 12.4 Hz,t =1.988,P ＜ 0.05).UPDRS revealed that clinical improvement was 89.7％ for tremor,48.4％ for rigidity and 38.1％ for bradykinesia respectively.Conclusions The data support that neuronal oscillations in the Vop/Vim are involved in parkinsonian symptoms.Neurons with TFB oscillation high densely distributed in the Vim indicate that the Vim is the best target for tremor.Since neurons with βFB oscillation are associated with bradykinesia,and the Vop is presumed pallidal relay nucleus.It is likely that the Vop is effective for parkinsonian bradykinesia/rigidity. Key words: Parkinson' s disease; Ventral thalamic nuclei; Microelectrodes; Neurons ; Oscillation

Targeting accuracy of transcranial magnetic resonance–guided high-intensity focused ultrasound brain therapy: a fresh cadaver model

This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads. 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. 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. 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.

Is There a Role for Combined EMG-fMRI in Exploring the Pathophysiology of Essential Tremor and Improving Functional Neurosurgery?

BackgroundFunctional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.ObjectiveAim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.MethodsSimultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.ResultsAnalysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.ConclusionEMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.

Effects of inhalation of isoflurane at different time points on hypoxic-ischemic brain injury in neonatal rats

Objective To investigate the effects of inhalation of isoflurane at different time points on hypoxic-ischemic brain injury in neonatal rats.Methods One hundred and eighty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 6 groups (n =30 each):sham operation group (group Ⅰ),cerebral hypoxia/ischemia (H/I) group (group Ⅱ),and inhalation of isoflurane at different time point groups (groups Ⅲ-Ⅵ).Brain ischemia was induced by double ligation of left common carotid artery followed by inhalation of 8 ％ O2 + 92 ％ N2 for 2 h at 37 ℃.In groups Ⅲ,Ⅳ,Ⅴ and Ⅵ 1.5 ％ isoflurane was inhaled for 30 min starting from 0,3,6,12 h after H/I respectively,while the rats were exposed to 30％ O2 and 70％ N2 only in groups Ⅰ and Ⅱ.The survival rate at 7 days after H/I was recorded.The animals were sacrificed at 7 days after H/I.The brains were removed and the right and left cerebral hemispheres (CH) were weighed separately.The ratio between left/right CH was calculated.The density of normal neurons in ventral posterior inferior thalamic nucleus and posterior cingulate cortex in left and right CH were measured and the ratio of the density of normal neurons in the left to right CH was calculated.Results Compared with group Ⅰ,the weight of left cerebral hemisphere,ratio between left/right CH,and ratio of the density of normal neurons in the left to right CH were significantly decreased in other five groups (P ＜ 0.05).Compared with group Ⅱ,the weight of left cerebral hemisphere,ratio between left/right CH,and ratio of the density of normal neurons in the left to right CH were significantly increased in groups Ⅲ,Ⅳand Ⅴ (P ＜ 0.05).There were no significant differences in the indices nentioned above among groups Ⅲ,Ⅳand Ⅴ (P ＞ 0.05).There was no significant difference in the survival rate among groups Ⅱ-Ⅵ (P ＞ 0.05).Conclusion Inhalation of 1.5％ isoflurane for 30 min within 6 h after cerebral H/I can reduce the cerebral injury in neonatal rats. Key words: Isoflurane; Hypoxia-ischemia, brain; Infant, newborn

Changes in brain functional magnetic resonance imaging during noxious electric stimulation of forepaw and

Objective To investigate the change in brain functional magnetic resonance imaging (fMRI)during noxious electric stimu lation of forepaw and tail in rats.Methods Forty-eight healthy SD rats of both sexes weighing 300-450 g which responded sensitively to electrical stimulation as shown by Y-maze were randomly divided into 2 groups ( n =24 each) receiving nociceptive electric stimulation of left forepaw (group LF) and tail (group T) respectively.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 250-300 mg/kg.Brain fMRI was performed at 30 min after disappearance of righting reflex in both groups when electric stimulations were delivered intermittently to forepaw or tail.The images were analyzed with SPM2 software.Results Primary and secondary somatosensory cortex,posterior cingutate cortex,amygdaloid nucleus and ventral posterolateral thalamic nucleus were activated in group T.Right accumbens nucleus,right primary somatosensory cortex,right ventral posterolateral thalamic nucleus and right posterior cingutate cortex were activated in group LF.Conclusion Different brain areas are activated by noxious electric stimulation of different parts of body as shown by brain fMRI. Key words: Physical stimulation; Magnetic resonance imaging; Brain

NOCICEPTIVE RESPONSES OF THE LATERAL THALAMIC NUCLEUS EVOKED BY PINCH IN ANESTHETIZED RATS

Pinch was used as a noxious stimulus and applied to the tail and hindlimbs of rats to investigate the nociceptive responsiveness of neurons in the lateral thalamus. Pinch stimuli were applied with calibrated pincher, and glass micropipettes filled with 3 M NaCl served as recording electrodes. The lateral thalamus of six rats under ketamine anesthesia was probed, including the ventrobasal (VB) complex and the posterior thalamic nucleus ( Po ), while the noxious stimulus was applied. Neuronal responses in the lateral thalamus were identified with the aid of an audio monitoring device and an oscilloscope, and several inclusion criteria had to be met. A total of 168 neurons were studied across the ventral posterolateral thalamic nucleus (VPL), ventral posteromedial thalamic nucleus (VPM), and Po of the thalamus. Of the neurons assessed in the lateral thalamus, 38 responded to the nociceptive stimuli, and most were located within the Po region of the thalamus. Very few were located in the VB. The number of responsive neurons in the anterior region of the lateral thalamus was significantly greater than the number of responsive neurons in the posterior region of the lateral thalamus. This finding indicates that the anterior region of the lateral thalamus, especially the Po area, may respond more vigorously to noxious stimuli than the posterior region.

Unilateral Thalamic Deep Brain Stimulation for Disabling Kinetic Tremor in Multiple Sclerosis

Surgical options of multiple sclerosis (MS) tremor treatment are limited and narrowed to thalamotomy or deep brain stimulation of the thalamic nucleus ventralis intermedius. Lack of qualification protocol frequently results in poor outcome. To determine prospectively the efficacy and safety of unilateral ventralis intermedius deep brain stimulation as a tool to control disabling kinetic arm tremor related to MS. Neurological and neuropsychological evaluations were performed 1 month and 1 day before surgery and 1, 3, and 6 months after surgery. The evaluation included measurement of tremor and dexterity, Extended Disability Status Scale, Mini Mental State Examination, and quality-of-life assessment. Nine consecutive patients were enrolled in the group. Mean age at the time of surgery was 38.9 ± 9 years; median Extended Disability Status Scale at baseline was 7.1. Mean MS duration was 11.7 years, and mean tremor duration was 6.11 years. Mean postural and kinetic scores and hand capacity were measured. One month after surgery, median scores off and on stimulation were 12 and 6 for postural tremor, 12 and 10.5 for kinetic tremor score, 12 and 7.5 for manual capacity, and 22 and 20 for functional handicap, respectively. Similar results were 10 and 4, respectively, at the 3-month follow-up. Six months after surgery, median scores off and on stimulation were 10.4 and 4 for postural tremor and 12 and 7.8 for kinetic tremor, respectively. This prospective study confirms the value and safety of ventralis intermedius deep brain stimulation for treatment of kinetic tremor related to MS. Accurate and precise presurgical qualification plays a key role in successful treatment.

Deep Brain Stimulation in Benign Tremulous Parkinsonism

Benign tremulous parkinsonism (BTP) is characterized by prominent resting plus action tremor, mild parkinsonism with limited disability or progression apart from tremor, and a less-robust response to levodopa therapy. This disorder has an uncertain pathophysiologic relationship to idiopathic Parkinson disease. Deep brain stimulation (DBS) should be efficacious for this condition, but there is no previously published experience. To assess the clinical outcomes and surgical complications of patients with BTP who underwent DBS. Retrospective case series. Tertiary care medical center. Twelve men and 3 women with BTP who underwent DBS for levodopa-refractory tremor. Tremor status after DBS, preoperative vs postoperative scores on the Fahn-Tolosa-Marin tremor scale, and the presence of adverse events. Of the 15 patients, 8 underwent unilateral thalamic nucleus ventralis intermedius (VIM), 4 bilateral VIM, and 3 bilateral subthalamic nucleus DBS. At last follow-up at a median of 4 years post-DBS, 7 patients were tremor free, 6 had only trace tremor, and 2 were definitely improved but with residual tremor. The median preoperative Fahn-Tolosa-Marin tremor scale score was 17 (range, 11-21); the tremor scale score at the last videotaped follow-up was 1 (range, 0-6). Median time between the 2 videotapes was 11.5 months (range, 3-14 months). No patients experienced adverse events after the surgical procedure. These findings support the efficacy of DBS, with VIM and STN targets, in medically refractory BTP-related tremor. Further studies are needed to explore the long-term durability of response and to better compare the surgical targets.

「最近の脳科学」脳深部刺激療法（ＤＢＳ）

Deep brain stimulation (DBS) is an important component of the therapy for movement disorders and intractable pain. In Japan, the first case of DBS for controlling central pain syndrome was experienced in 1979 and DBS of the thalamic nucleus ventralis caudalis and periaqueductal gray matter have been used for pain control for many years. Neurosurgeons also initiated a clinical trial of DBS for controlling movement disorders, such as tremor, Parkinson′s disease (PD) and dystonia. Our government approved DBS to be covered by the public insurance system for pain control in 1992 and for movement disorders in 2000. In particular, DBS for subthalamic nucleus (STN) is currently the most common therapeutic surgical procedure for patients with PD. The long-lasting beneficial effects of STN-DBS on motor function have now largely been acknowledged. However, behavioral and/or psychiatric changes have been demonstrated in certain case reports and case series. DBS is also a successful therapeutic option for patients with primary dystonia and tremor syndrome who do not respond sufficiently to conservative therapies. The most common target of DBS in patients with dystonia is the internal region of the globus pallidus (GPi). GPi-DBS leads to long-lasting and remarkable improvement of dystonic movements in majority of patients. In Parkinson′s tremor or post-stroke movement disorder, the intermediate ventral nucleus of the thalamus (Vim) and the subthalamic region have proven to be promising targets for DBS electrodes. Especially in patients with essential tremor, Vim-DBS leads to an acute reduction of the tremor. In addition, DBS is beginning to be used as a new therapeutic procedure for psychiatric diseases, such as depression and obsessive-compulsive neurosis in many countries. We will summarize our experiences and previous reports, and discuss the mechanism and future perspectives for DBS in the management of central nervous system disorders.

Effects of age and gender on Sirt 1 mRNA expressions in the hypothalamus of the mouse

Sirt1 is a NAD-dependent deacetylase that has been shown as a link between energy metabolism and aging. Its putative role as a target for neurodegenerative disorders has recently been suggested; yet, little is known about the changes that occur in Sirt1 levels in the aging brain. Here we show by in situ hybridization that Sirt1 expression is modified in specific areas of the brain in mice upon aging, and that gender also impacts on this regulation. Mice aged 12 and 24 months had a lower Sirt1 expression specifically in the antero ventral thalamic nucleus (AV) and in the arcuate nucleus (ARC) than their young (4 mo) counterparts, whereas changes were either not noticeable or not significantly modulated in other parts of the brain. Regulation of Sirt1 mRNA levels in the subfornical organ (SFO) and in the substancia nigra part compacta (SNC) depended on gender. These findings suggest that reduced Sirt1 levels upon aging could contribute to a lower Sirt1 activity, and that specific nuclei might be particularly affected.

Thalamic deep brain stimulation for tremor among multiple sclerosis patients

Background and purposeDisabling tremor might be the main cause of disability of multiple sclerosis (MS) patients. Neuromodulation with deep brain stimulation of the thalamic nucleus ventralis intermedius (Vim DBS) is a well accepted method of neurosurgical treatment of tremor related to essential tremor or Parkinson disease. Vim DBS is not widely used to control MS tremor. Material and methodsFive MS patients with tremor (3 females and 2 males) were treated with Vim DBS. Age at implantation was 37 ± 5 years. MS lasted from 5 to 12 years (mean 6) and tremor was the main cause of disability of those patients from 2 to 5 years (mean 3) before surgery. Clinical condition of the group was evaluated with spirography, the modified Fahn scale and the modified Activity of Daily Living (ADL) scale. Evaluations were performed before surgery and 3 months after surgery. MRI exclusion criteria were the presence of a thalamic hyperintense signal in T2-weighted images or ventricular enlargement. The procedures of implantation were performed under local and general anaesthesia. ResultsIntensity of contralateral limb tremor during intraoperative macrostimulation was reduced in the whole group. The therapeutic effect of DBS was maintained at three-month follow-up. Mean contralateral limb tremor reduction was 40%. Mean ADL score improved by 18%. No mortality or morbidity was reported in the group. ConclusionsThe study confirms the value and safety of Vim DBS for treatment of MS-related tremor. Further study on a larger population and introduction of a qualification protocol might increase efficacy of the treatment.

P3.068 Basal ganglia hyperindirect pathway: direct projections from the subthalamic nucleus innervating the ventral motor thalamic nuclei in MPTP-treated primates

P3.068 Basal ganglia hyperindirect pathway: direct projections from the subthalamic nucleus innervating the ventral motor thalamic nuclei in MPTP-treated primates

MR Imaging of Ventral Thalamic Nuclei

The Vim and VPL are important target regions of the thalamus for DBS. Our aim was to clarify the anatomic locations of the ventral thalamic nuclei, including the Vim and VPL, on MR imaging. Ten healthy adult volunteers underwent MR imaging by using a 1.5T whole-body scanner. The subjects included 5 men and 5 women, ranging in age from 23 to 38 years, with a mean age of 28 years. The subjects were imaged with STIR sequences (TR/TE/TI = 3200 ms/15 ms/120 ms) and DTI with a single-shot echo-planar imaging technique (TR/TE = 6000 ms/88 ms, b-value = 2000 s/mm(2)). Tractography of the CTC and spinothalamic pathway was used to identify the thalamic nuclei. Tractography of the PT was used as a reference, and the results were superimposed on the STIR image, FA map, and color-coded vector map. The Vim, VPL, and PT were all in close contact at the level through the ventral thalamus. The Vim was bounded laterally by the PT and medially by the IML. The VPL was bounded anteriorly by the Vim, laterally by the internal capsule, and medially by the IML. The posterior boundary of the VPL was defined by a band of low FA that divided the VPL from the pulvinar. The ventral thalamic nuclei can be identified on MR imaging by using reference structures such as the PT and the IML.

The distribution of GAD67‐mRNA in the adult zebrafish (teleost) forebrain reveals a prosomeric pattern and suggests previously unidentified homologies to tetrapods

We used in situ hybridization on sections to examine the distribution of GAD67-expressing cell populations in the entire forebrain of the adult zebrafish. GAD67 is predominantly expressed in the olfactory bulb (OB), all regions of the subpallium (including the dorsal, ventral, central, and lateral nucleus of the area ventralis [Vd, Vv, Vc, and Vl, respectively]), as well as preoptic (PPa, PPp, and PM), pretectal (PPd, PPv, PCN, PSp, and PSm), ventral (= pre-) thalamic (I, VM, and VL), hypothalamic (Hr, Hi, and Hc), preglomerular (P, PGa, PGl, PGm, and RT), and posterior tubercular (TPp and TPm) nuclei. Only scattered GAD67-expressing cells are seen in all pallial zones (Dm, Dd, Dc, Dl, and Dp) and in the previously unidentified bed nucleus of the stria medullaris (BNSM). The BNSM appears to be the adult teleostean derivative of the larval eminentia thalami (EmT). We identify the GAD67-positive entopeduncular nucleus proper (EN) as being homologous to the entopeduncular nucleus of nonprimate mammals. GAD67 is strongly expressed in the anterior thalamic nucleus (A). The anterior thalamic nucleus is laterally bordered by a distinct GAD67-expressing cell population, which we interpret as the previously unidentified reticular thalamic nucleus (RTN) of teleosts. Furthermore, we identified a GAD67-positive thalamic nucleus, the intercalated nucleus (IC), which is sandwiched between the GAD67-negative dorsal (DP) and central posterior (CP) thalamic nuclei. Overall, the distribution of GAD67-expressing cells highly resembles the distribution of gamma-aminobutyric acid (GABA)/GAD67-expressing cells found in the early zebrafish (teleost) forebrain and thus allows us to propose a prosomeric fate map of GABAergic cell populations.

Expression of Frizzled10 in mouse central nervous system

Frizzled transmembrane proteins (Fzd) are receptors of Wnts, and they play key roles during central nervous system (CNS) development in vertebrates. Here we report the expression pattern of Frizzled10 in mouse CNS from embryonic stages to adulthood. Frizzled10 is expressed strongly at embryonic days E8.5 and E9.5 in the neural tube and tail bud. At E10.5, Frizzled10 is expressed in the forebrain vesicle, the fourth ventricle and the dorsal spinal cord. From E12.5 to E16.5, Frizzled10 expression is mainly observed in the cortical hem/fimbria, the neuroepithelium of the third ventricular zone, midbrain, developing cerebellum, and dorsal spinal cord. At P0, with the exception of expression in the fimbria, Frizzled10 mRNA expression is limited to specific nuclei including the ventral posterior thalamic nucleus (VP) and the dorsal lateral geniculate nucleus (DLG) in the developing thalamus as well as in the proliferative ventricular zone of the developing cerebellum. From P20 to adult, Frizzled10 mRNA is detected only in the internal capsule (ic). Our data show that expression of Frizzled10 is very strong during embryonic development of the CNS and suggest that Frizzled10 may play an essential role in spatial and temporal regulation during neural development.

Long-term electrical inhibition of deep brain targets in movement disorders.

Stimulation of the thalamic nucleus ventralis intermedius (Vim) at high (130-Hz) frequency has been used over the last 8 years as a treatment in 134 patients with movement disorders (91 Parkinson's disease [PD], 23 essential tremor [ET], 21 various dyskinesias and dystonias, including four multiple sclerosis [MS]), implanted with long-term electrodes connected to a programmable stimulator. In PD patients, tremor was selectively suppressed for < or = 11 years. In ET patients, results were satisfactory, but in 35% of the cases deteriorated with time, when tremor had an action component. Other types of dyskinesias were much less influenced. Sixty-eight patients were bilaterally implanted, and 14 were implanted contralateral to a previous thalamotomy. Side effects were often minor, well tolerated, and immediately reversible. Three secondary scalp infections led to temporary removal of implanted material. There was no permanent morbidity. Long-term Vim stimulation, which is reversible, adaptable, and well tolerated, even by bilaterally operated-on (68 of 134) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors. More recently, we stimulated the subthalamic nucleus (STN) in 51 patients (44 bilateral) and the globus pallidus internus (GPi) in 12 patients (seven bilateral). STN stimulation has a spectacular effect on akinesia and rigidity and may improve the patients so as to maintain them all day at a level similar to their best "on" periods. A 30-50% reduction in drug dosage was possible in most of the patients. GPi stimulation has indications and effects similar to those of pallidectomy: abnormal involuntary movements are totally suppressed, whereas effects on akinesia and rigidity are not so important as they are with STN stimulation. For all three targets, morbidity is low and reversible, even when bilateral implantations are performed. The deep-brain stimulation method has now proved its safety as compared with ablative surgery and is able to provide a significant improvement to these severely disabled patients. Long-term follow up is establishing the security of the method, which should be considered in earlier stages of the disease actively to participate to rehabilitation.

Thalamic projections to the posteromedial cortex in the macaque

The medial parietal, posterior cingulate, and retrosplenial cortices collectively constitute a region of cortex referred to as the posteromedial cortices (PMC). In an effort to shed light on the neuroanatomical organization of the PMC, we undertook a study to identify and analyze the thalamocortical connections of these cortices. Retrograde tracer injections were placed in the posterior cingulate (PCC), retrosplenial (RSC), medial parietal cortices (MPC), and posterior cingulate sulcus (PCS), and the labeling patterns within the thalamus were analyzed. Three afferent projection patterns were observed to the PMC from the thalamus: a PCC/RSC pattern that involved the anterior thalamic nuclei, an MPC pattern that involved the lateral posterior and pulvinar nuclei, and a PCS pattern that involved the ventral thalamic nuclei. Additionally, a shared pattern of projections from the anterior intralaminar nuclei (AILN) and posterior thalamic nuclei (PTN) to all cortical regions of the PMC was observed. Our findings suggest that distinct regions within the PMC are supplied by distinctive patterns of thalamic input, but also share common projections from intralaminar and posterior thalamic sources. In addition, we relate our findings to functional abnormalities in aging and dementia, and address a domain-like pattern of thalamocortical labeling of the PMC that is drawn selectively and collectively from multiple thalamic nuclei.