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[Observation of pathological morphology on nervous system of rat with maximum dose sophoridine in chronic toxic test].

BACKGROUND & OBJECTIVE: Sophoridine is a new anticancer drug with noticeable antitumor action and lower toxicity. No marked influence on bone marrow was found till now. The main toxicity is presented in nervous system. This study was to observe the morphological changes of the nervous system of the rats, which were treated with maximum dose of sorphoridine for a long time. METHODS: 30 rats,half of male when and half of female, were randomly divided into experimental group and control group. In the experimental group,rats were treated with maximum dose of sorphoridine [32 mg x(kg x d)(-1) ip, qd] for 60 days. In control group, rats were treated with the same volume of saline everyday for 60 days. The rats in both groups were killed at 20 d, 40 d, 60 d, and 75 d, respectively. The brain and spinal cord were taken out and made into pathological slices, which were stained by HE stain and special stain, sach as Nissel's body stain, glial fibrillary stain and myelin sheath stain. The differences in morphology between the two groups was observed. RESULTS: No pathological change was found in rats' cerebral cortex,internal capsul, striated body, hippocampus, substantia nigra,and spinal cord when the rats' were treated with sophoridine 32 mg x(kg x d)(-1) ip for 20 d, 40 d, 60 d. In the rats who had presented nervous system syndrome repeatedly or died for convulsion, or the rats who were killed in convalescence period (15 d after final administration), there was no pathological change either. CONCLUSION: No pathological changes and delayed changes in the nervous tissues were found when the rats were given maximum dose of Sophoridine continuously for 60 d. Our study showed that the syndrome of nervous system caused by Sophoridine is functional and stimulational, and can be recovered,and there is no any delayed change and sequela.

Alkaloids↗

Deep brain stimulation for pain relief: a meta-analysis.

Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.

Animals↗

An axotomy model for the induction of death of rat and mouse corticospinal neurons in vivo.

To study trophic dependencies of rat and mouse corticospinal neurons (CSN), we established a lesion model for the induction of death of analogous populations of CSN in these rodent species. Before lesion, CSN were retrogradely labeled with Fast Blue (FB). A stereotaxic cut lesion through the entire internal capsule (ICL) was used to axotomize CSN. The extent of axotomy was determined by application of a control tracer. In both species, FB-labeled CSN were localized in three major areas: (1) the sensory motor cortex; (2) the supplementary motor and medial prefrontal cortex; and (3) the somatosensory cortex. ICL does not lead to complete axotomy of CSN of the rat and mouse somatosensory cortex. In rats, ICL results in complete axotomy of CSN of the sensory motor cortex and incomplete axotomy of the caudal portion of the supplementary motor and medial prefrontal cortex. In mice, the area of axotomized CSN extends significantly further frontally. In both species, axotomy-induced death of CSN is observed in the center of the sensory motor cortex. This lesion model is useful for investigations on the response of CSN of the sensory motor cortex to lesion and therapeutic drugs.

Animals↗

Age-associated changes of cerebral glucose metabolic activity in both male and female deaf children: parametric analysis using objective volume of interest and voxel-based mapping.

Quantitative analysis of brain activity in the brains of children requires the establishment of age-associated norms. We investigated regional differences in age-associated changes in fluorodeoxyglucose (FDG) uptake in the developmental brains. From 87 (44 male and 43 female) deaf children from the age of 1 to 15, brain FDG positron emission tomography (PET) images were examined after spatial normalization, smoothing, and global normalization to identify brain regions showing a correlation between FDG uptake and age. Using population-based probabilistic volume of interests (VOIs), an objective VOI analysis was performed where normalized relative FDG uptake was measured and their correlations with age were examined in both genders. For the voxel-based analyses, the correlations with age were examined in a general linear model using statistical parametric mapping (SPM99). Both methods revealed that FDG uptake linearly increases with age both in the bilateral inferior prefrontal/orbitofrontal gyri and the right dorsomedial frontal gyrus and decreases in the inferior temporal gyrus and internal capsule white matter. Male children showed age-associated increases of FDG uptake in the right dorsomedial frontal gyrus, and female children in the left dorsolateral prefrontal cortex and thalamus. These changes in FDG uptake in various brain regions may suggest changes in synaptic density or regional activity resulting from normal maturation or deaf-induced adaptation. Caution should be exercised in interpreting the differences in the brain of child patients when compared with adult control's or with a different gender. Further research will be needed to examine if gender difference is manifested in the development rate of behavioral/cognitive functions in association with the age-associated changes of the right medial frontal (male) or the left dorsolateral prefrontal cortices.

Adolescent↗

Identification of motor pathways during tumor surgery facilitated by multichannel electromyographic recording.

OBJECT: The goal of this study was to determine the usefulness of electromyographic (EMG) recording in locating motor pathways near the central sulcus or internal capsule during surgery. METHODS: Multichannel EMG recordings were compared with visual observation of contralateral body movement that was elicited by direct cortical or subcortical stimulation used to identify motor pathways before and during tumor resection. The EMG recordings were more sensitive than visual observation alone in identifying motor responses: in 30% of cases, responses were identified by EMG recording alone at some point during the operation and, in 9% of cases, EMG responses were the only responses observed. Additionally, EMG recordings often detected seizure activity resulting from electrical stimulation of the cortex that could not be appreciated on visual inspection. No new motor deficits were seen postoperatively in 88% of the patients in this series. CONCLUSIONS: Using EMG recording in addition to motor pathway mapping results in greater sensitivity, allowing the use of lower stimulation levels and facilitating detection of stimulation-induced seizure activity.

Adolescent↗

[Cerebral ischemia following varicella. A case report].

INTRODUCTION: Varicella in childhood is a self-limiting disease which usually follows a benign course. However, a considerable number of complications occur, particularly involving the nervous system. On rare occasions hemiparesis has been reported following an ischemic cerebrovascular accident related to varicella. CLINICAL CASE: We report the case of a 4 year old boy who presented with right hemiparesis eight days after the onset of varicella. CAT and MR showed a cerebral infarct involving the left caudate nucleus, putamen and internal capsule. Other possible causes of cerebral infarct were ruled out. Four years later he had slight residual right hemiparesis. The pathogenesis may have been due to vasculitis of the intracranial arteries caused by direct invasion of the vessels by virus from the nearby nerve tissue. Another theory suggest similarities with moyamoya disease, suggesting that lesions of the head and neck stimulate the superior cervical ganglion and this, together with the production of circulating immuno-complexes may be the cause of the vasculopathy of the intracranial blood vessels. CONCLUSIONS: In most cases of cerebrovascular accidents occurring in childhood the cause is unknown. However, it is important to discover the cause since the risk of recurrence often depends on the primary disease. Once other commoner causes have been excluded, one should ask whether there is a history of varicella, since the prognosis is generally good and recurrence uncommon.

Brain Ischemia↗

Assessment of white matter damage in subacute sclerosing panencephalitis using quantitative diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: Subacute sclerosing panencephalitis (SSPE), a rare progressive degenerative disease, is caused by persistent infection with a defective measles virus. The correlation between the clinical staging and MR imaging is usually poor. The aim of the study was to investigate the role of diffusion tensor imaging (DTI) in the early detection of white matter damage in SSPE in the presence of normal findings on conventional imaging. METHODS: DTI was performed in 21 patients in stage II SSPE and 10 age/sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in the periventricular white matter, corpus callosum, and posterior limb of the internal capsule in patients with normal and abnormal findings on conventional imaging as well as healthy controls. RESULTS: The patients were grouped into those with normal (n = 11) and abnormal (n = 10) findings on conventional imaging for the purpose of quantitative DTI analysis. Abnormal- and normal-appearing white matter on T2-weighted images showed significantly decreased FA values in all the regions compared with those in healthy controls. MD values were significantly increased in the periventricular white matter region of the frontal and parietooccipital lobe in patients with normal as well as abnormal findings on conventional imaging compared with those in healthy controls. CONCLUSION: DTI detects early white matter abnormalities that may have significant therapeutic implication, even in the presence of normal findings on conventional imaging, in patients with SSPE.

Adolescent↗

Neural substrate of antisaccades: role of subcortical structures.

BACKGROUND: Experimental and clinical studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the superior colliculus (SC) are crucial for the cancellation of reflexive eye movements toward distracting stimuli. However, the contribution of subcortical structures remains unknown. The basal ganglia provide serial tonic inhibitory connections between the DLPFC and the SC, and could therefore be involved in preventing the triggering of unnecessary saccades. The DLPFC could also exert its inhibitory effect on the SC through direct prefronto-tectal pathways that travel in the internal capsule (IC). Since thalamic dysfunction may be responsible for reduced DLPFC activation, it may be hypothesized that the thalamus could also participate in saccadic inhibition. METHODS: The authors recorded reflexive saccade triggering (prosaccade task) and inhibition (antisaccade task) in 29 patients with a single lesion affecting the striatum, the thalamus, or the IC, and compared these results to control subjects. RESULTS: A normal error rate in the antisaccade task was found in patients with 1) a basal ganglia lesion, 2) a thalamic lesion, or 3) a lesion restricted to the posterior half of the posterior limb of the IC. An increased error rate in the antisaccade task was found in patients with a lesion affecting the anterior limb, the genu, or the anterior half of the posterior limb of the IC. CONCLUSION: These results suggest that neither the basal ganglia nor the thalamus plays a major role in reflexive saccade suppression, but support the hypothesis of a direct DLPFC inhibitory control of saccade triggering on the SC.

Adult↗

Diffusion anisotrophy in the early stages of stroke can predict motor outcome.

PURPOSE: This study examined whether the degree of impairment of diffusion anisotrophy in the early stages of a stroke can predict the motor function outcome. METHODS: Thirty-one hemiplegic stroke patients were enrolled to this study. Diffusion anisotropy was measured by determining fractional anisotropy (FA) in the two ROIs (region of interests) at corona radiata (CR) and in the posterior limb of internal capsule (IC) during the early stages of stoke (average 7.9 days after stroke onset) and compared with motor outcome of the affected hand 3 months after stroke onset. RESULTS: Both ROIs (CR or IC) and lesion types (hemorrhage or infarction) did not have significant effect on the SBFA (symmetry of bilateral FA) and dMRC (medical research council score improvement), either. Patients with greater initial MRC score had significantly greater SBFA and dMRC. The regression equation between the dMRC (Y axis) and the SBFA (X axis) was semi-linear and significant (P < 0.05); for CR group, Y = 3.296 - 0.1192X + 0.0015X2; for IC group, Y = 2.342 - 0.0533X +0.0007(2). The regression lines had 'threshold points' where a minute SBFA change would make a steep increase in dMRC. CONCLUSION: The degree of impairment in diffusion anisotropy during the early stages of stroke appears to have the potential to predict motor outcome.

Analysis of Variance↗

Anatomical examination of the recurrent artery of Heubner.

There is considerable inconsistency in the description of the origins, dimensions, and course of the recurrent artery of Heubner (RAH). The RAH frequently supplies parts of the basal ganglia and the anterior limb of the internal capsule and can be damaged with improper clip placement during repair of aneurysms near the anterior communicating artery. Thus, further elaboration of the anatomical descriptions of the RAH is necessary. The gross anatomy of the RAH was studied in 69 human brain hemispheres. RAH was found as a single vessel in 53 hemispheres (77%), as double arteries in 12 hemispheres (17%), and was absent in 4 hemispheres (6%). The origin of the RAH was from the junction of the anterior cerebral artery and anterior communicating artery in 48 (62.3%) hemispheres, from the proximal A2 segment of the anterior cerebral artery in 18 (23.3%) hemispheres and from the A1 segment in 11 (14.3%) hemispheres. The diameters of the artery ranged from 0.2 to 1.3 mm with a mean of 0.8 mm, while the length ranged from 0.9 to 3.8 cm with a mean of 2.4 cm. The above data may provide important information to neurosurgeons operating in this area, as well as to neuroanatomists teaching the vascular supply of the brain.

Anterior Cerebral Artery↗

Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures.

Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.

Adult↗

A diffusion tensor imaging study of white matter in obsessive-compulsive disorder.

Our objective was to test for differences between subjects with obsessive-compulsive disorder (OCD) and healthy controls with respect to white matter architecture within the cingulum bundle (CB) and anterior limb of the internal capsule (ALIC). We studied eight subjects with active OCD and 10 matched healthy controls using diffusion tensor magnetic resonance imaging (DT-MRI) at 1.5 T (Tesla). Fractional anisotropy (FA) was evaluated in both CB and ALIC. Both voxelwise and region-of-interest methods of analysis were employed. Within both the left CB and the left ALIC, subjects with OCD exhibited significantly greater FA than healthy controls. In the right CB, subjects with OCD exhibited significantly decreased FA versus healthy control subjects. Additionally, the OCD group exhibited abnormal asymmetry (left > right) of FA in the CB. These results provide preliminary evidence for abnormal architecture within the CB and ALIC in OCD. FA differences in these areas are consistent with the presence of abnormal connections between the nodes linked by these tracts. This could explain why surgically severing these tracts is therapeutic. Additional studies are needed to replicate these findings and to clarify their pathological and clinical significance.

Adolescent↗

Basilar artery stenosis mimicking the lacunar syndrome of pure motor hemiparesis.

BACKGROUND: Stereotyped, repeated transient ischemic attacks manifesting as pure motor hemiparesis are most often attributed to ischemia of the internal capsule or ventral pons resulting from in situ disease of the small penetrating arteries. CASE DESCRIPTION: We report a 61-year-old man presenting with recurrent episodes of left-sided weakness consistent with the lacunar syndrome of pure motor hemiparesis. Subsequent neuroimaging revealed infarction of the right ventral pons and a critical basilar artery stenosis as the inciting lesion. Despite maximal antithrombotic therapy, he continued to have repeated symptoms. Angioplasty and stenting were attempted but both failed due to plaque recoil and technical difficulties. After the procedure, the patient had no further ischemic episodes and remained symptom-free at two months. CONCLUSIONS: This case illustrates the imprecise and discordant relationship between the mode of presentation of a stroke syndrome and its presumed pathophysiology. The lacunar syndrome of pure motor hemiparesis should be recognized by clinicians as a mode of stroke presentation due not only to small vessel disease, but also to large artery atherosclerotic disease such as basilar artery stenosis. Prompt institution of treatment can lead to a good clinical outcome.

Angioplasty, Balloon↗

Ipsilateral motor pathway confirmed by combined brain mapping of a patient with hemiparetic stroke: a case report.

This study investigated the motor control pathway using both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in a patient with left hemiparesis with an infarction on the posterior limb of the right internal capsule. fMRI was performed using the blood oxygen level-dependent technique at 1.5 T with a standard head coil. The motor activation task consisted of hand grasp-release movements in 1-Hz cycles. TMS was performed using a butterfly coil; the intersection of the wings (center of the coil) was applied tangentially to the scalp 1.0 cm apart. Stimulation was performed at 100% of maximal output. Motor evoked potentials (MEPs) from both abductor pollicis brevis (APB) muscles were obtained simultaneously. fMRI showed that the unaffected (left) primary sensorimotor cortex (SM1) was activated by movements of the unaffected (right) hand. Conversely, the bilateral SM1 were activated by movements of the affected (left) hand. Brain mapping using TMS showed that ipsilateral MEPs were obtained at the affected (left) APB muscle when the unaffected (left) motor cortex was stimulated. We concluded that the ipsilateral motor pathway from the unaffected motor cortex to the affected hand was present in this patient.

Activities of Daily Living↗

Diffusion anisotropy changes in the brains of professional boxers.

BACKGROUND AND PURPOSE: Professional boxing may result in brain injury. We hypothesize that quantitative MR diffusion imaging may be useful in determining early white matter changes. METHODS: Forty-nine professional boxers (age 30 +/- 4.5 years) and 19 healthy control subjects (age 32 +/- 9.5 years) were imaged on a clinical 1.5T scanner. None of the subjects had neurologic disorder or deficit. The average diffusion constant (D(av)) and diffusion anisotropy (FA) were determined pixel by pixel. Regional diffusion measurements were done in the corpus callosum (CC) and internal capsule (IC). The whole brain diffusion constant (BD(av)) was also determined. Student t test was used to analyze the diffusion difference between boxers and the healthy control subjects. P < .05 was considered statistically significant. RESULTS: Of the 49 professional boxers, 42 had normal conventional MRIs. The remaining 7 boxers had abnormal MR imaging findings dominated by nonspecific white matter disease. There was a significant difference in diffusion and anisotropy measurements in all the boxers compared with the healthy control subjects. In the boxer group, BD(av) increased and FA decreased significantly in the CC and posterior limb of IC. The measured FA and D(av) inversely correlated in regions of CC and IC in boxers but not in healthy control subjects. BD(av) also robustly correlated with both FA and D(av) in the splenium of CC in boxers. CONCLUSION: Increased BD(av) and the decreased FA in the CC and IC may represent preclinical signs of subtle brain injury in professional boxers.

Adult↗

An application of upper-extremity constraint-induced movement therapy in a patient with subacute stroke.

BACKGROUND AND PURPOSE: The purpose of this case report is to demonstrate the application of constraint-induced movement therapy with an individual with upper-extremity hemiparesis within 4 months after sustaining a cerebrovascular accident (stroke). Such patients often fail to develop full potential use of their affected upper extremity, perhaps due to a "learned nonuse phenomenon." CASE DESCRIPTION: The patient was a 61-year-old woman with right-sided hemiparesis resulting from an ischemic lacunar infarct in the posterior limb of the left internal capsule. The patient's less-involved hand was constrained in a mitten so that she could not use the hand during waking hours, except for bathing and toileting. On each weekday of the 14-day intervention period, the patient spent 6 hours being supervised while performing tasks using the paretic upper extremity. Pretreatment, posttreatment, and 3-month follow-up outcome measures included the Wolf Motor Function Test and the Motor Activity Log (MAL). OUTCOMES: For the Wolf Motor Function Test, both the mean and median times to complete 16 tasks improved from pretreatment to posttreatment and from posttreatment to follow-up. Results of the MAL indicated an improved self-report of both "how well" and "how much" the patient used her affected limb in 30 specified daily tasks. These improvements persisted to the follow-up. DISCUSSION: Two weeks of constraining the unaffected limb, coupled with practice of functional movements of the impaired limb, may be an effective method for restoring motor function within a few months after cerebral insult. Encouraging improvements such as these strongly suggest the need for a group design that would explore this type of intervention in more detail.

Arm↗

Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T.

PURPOSE: To prospectively determine whether diffusion-tensor magnetic resonance (MR) imaging in conjunction with two-dimensional chemical shift imaging can assist in identifying upper motor neuron involvement and whether disease severity and duration can be predicted based on imaging parameters in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Fifteen patients with ALS (12 men, three women; mean age, 57.3 years) with clinical evidence of upper motor neuron involvement and 10 healthy control subjects (five men and five women; mean age, 49.4 years) were studied. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured from the corticospinal tracts at the level of the internal capsule. Average N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline-containing compounds (Cho) ratios were calculated from the precentral gyrus. Student t test, multiple linear regression analysis, and Spearman correlation coefficients were employed to quantify relationships between imaging and clinical parameters. RESULTS: Patients with ALS exhibited significantly reduced FA values and NAA/Cr and NAA/Cho ratios compared with values in control subjects (P<.05) for both affected and nonaffected sides of the brain. ADC was elevated significantly in the affected side (P<.05) and was an independent predictor of disease duration after adjusting for age; however, FA values and NAA/Cr ratios for the affected side were even stronger predictors of disease duration. Moderate but statistically significant correlation was found between the FA values for the affected side and the ALS Functional Rating Scale Revised (ALSFRS-R) score (r=0.51, P<.05). The NAA/Cr ratio also correlated with both the ALSFRS-R and upper motor neuron scores (r=0.50 and 0.54, respectively; P<.05). CONCLUSION: Diffusion-tensor and two-dimensional chemical shift MR imaging spectroscopy can be used to identify upper motor neuron involvement and predict disease duration in patients with ALS.

Adult↗

The thalamic reticular and perireticular nuclei in developing rabbits: patterns of parvalbumin expression.

Due to its strategic position, the thalamic reticular nucleus (TRN) plays an important role within the thalamo-cortical circuits. The perireticular thalamic nucleus (PRN) is a smaller group of cells, which is associated with the TRN and lies among the fibres of the internal capsule (IC). Studies of nuclei in rodents and carnivores have been conducted employing a number of different tools. The use of calcium-binding proteins is one example. It needs to be noted that rabbits have been regarded as intermediate between rodents and carnivores in relation to local GABAergic circuits. In the present study, sections from rabbits at different ages (prenatal, postnatal and adult) were examined to determine the parvalbumin (PV) expression in the developing TRN and PRN. In the TRN, there is one wave of PV expression during development, from caudal parts of the nucleus towards the rostral pole. At E22 there is already an incipient PV expression. In the adult stage, the TRN is completely positive to PV. The present study clearly indicates the presence of the PRN in the developing rabbit. The first PV positive cells were visible at E24, meanwhile the immunoreactivity was at its maximum at early postnatal stages (P0-P8). Two different types of perireticular cells in the IC were identified and the changes concerning neuronal morphology and orientation were described. The comparison between these results and previous data obtained in rats, ferrets or cats suggest that rabbits could represent an intermediate stage in the evolution of thalamic circuits and could be considered as useful neurobiological model.

Animals↗