Narrow Results

During the last decade, deep brain stimulation (DBS) has been used to treat several neurologic disorders, including epilepsy. Promising results have been reported with stimulation in different brain regions. At present however, several issues remain unanswered. As an example, it is still unclear whether particular seizure types and syndromes should be treated with DBS in different targets or with different stimulation parameters. In addition, clinical, electrophysiological and anatomical features capable of predicting a good postoperative outcome are still unknown. We review the published literature on DBS, cortical and cerebellar stimulation for the treatment of epilepsy focusing predominantly on the rationale and clinical outcome in each target.

The purpose of this study was to investigate the functional connectivity (FC) of thalamic subdivisions in patients with juvenile myoclonic epilepsy (JME). Resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired from 22 JME and 25 healthy controls. We first divided the thalamus into eight subdivisions by performing independent component analysis on tracking fibers and clustering thalamus-related FC maps. We then analyzed abnormal FC in each subdivision in JME compared with healthy controls, and we investigated their associations with clinical features. Eight thalamic sub-regions identified in the current study showed unbalanced thalamic FC in JME: decreased FC with the superior frontal gyrus and enhanced FC with the supplementary motor area in the posterior thalamus increased thalamic FC with the salience network (SN) and reduced FC with the default mode network (DMN). Abnormalities in thalamo-prefrontocortical networks might be related to the propagation of generalized spikes with frontocentral predominance in JME, and the network connectivity differences with the SN and DMN might be implicated in emotional and cognitive defects in JME. JME was also associated with enhanced FC among thalamic sub-regions and with the basal ganglia and cerebellum, suggesting the regulatory role of subcortical nuclei and the cerebellum on the thalamo-cortical circuit. Additionally, increased FC with the pallidum was positive related with the duration of disease. The present study provides emerging evidence of FC to understand that specific thalamic subdivisions contribute to the abnormalities of thalamic-cortical networks in JME. Moreover, the posterior thalamus could play a crucial role in generalized epileptic activity in JME.

Status epilepticus (SE) is a common, life-threatening neurological disorder that may lead to permanent brain damage. In rodent models, SE is an acute phase of seizures that could be reproduced by injecting with pilocarpine and then induce chronic temporal lobe epilepsy (TLE) seizures. However, how SE disrupts brain activity, especially communications among brain regions, is still unclear. In this study, we aimed to identify the characteristic abnormalities of network connections among the frontal cortex, hippocampus and thalamus during the SE episodes in a pilocarpine model with functional and effective connectivity measurements. We showed that the coherence connectivity among these regions increased significantly during the SE episodes in almost all frequency bands (except the alpha band) and that the frequency band with enhanced connections was specific to different stages of SE episodes. Moreover, with the effective analysis, we revealed a closed neural circuit of bidirectional effective interactions between the frontal regions and the hippocampus and thalamus in both ictal and post-ictal stages, implying aberrant enhancement of communication across these brain regions during the SE episodes. Furthermore, an effective connection from the hippocampus to the thalamus was detected in the delta band during the pre-ictal stage, which shifted in an inverse direction during the ictal stage in the theta band and in the theta, alpha, beta and low-gamma bands during the post-ictal stage. This specificity of the effective connection between the hippocampus and thalamus illustrated that the hippocampal structure is critical for the initiation of SE discharges, while the thalamus is important for the propagation of SE discharges. Overall, our results demonstrated enhanced interaction among the frontal cortex, hippocampus and thalamus during the SE episodes and suggested the modes of information flow across these structures for the initiation and propagation of SE discharges. These findings may reveal an underlying mechanism of aberrant network communication during pilocarpine-induced SE discharges and deepen our knowledge of TLE seizures.

A rapid and simple high-performance liquid chromatographic method for determination of berberine in rat thalamus was described in this study. Thalamus samples were pretreated by protein precipitation with methanol and acetonitrile. Berberine was determined using a Hypersil C₁₈ column with an isocratic mobile phase of acetonitrile — 0.05 M potassium dihydrogen phosphate (containing 0.5% triethylamine, pH 3.0) (30:70 v/v) and with UV detection at 265 nm. The lower limit of quantification for berberine in thalamus was 24 ng/ml, and the lowest concentration of berberine determined in rat thalamus samples was 47.5 ng/ml at 48 hours. The calibration curve for berberine was linear (r² = 0.9994) over the concentration range 24–6000 ng/ml. At this concentration range, the overall recoveries (91.20%–93.24%) for berberine were determined and the accuracy of the intra- and inter-day assays from rat thalamus were less than 6% RSD. Following intravenous administration of 10.2 mg/kg of Coptidis Rhizoma (CR) extract containing 3 mg/kg berberine into rats, the thalamus level of berberine increased rapidly (t_1/2α = 1.93 hours), peaked at 2.48 hours with a concentration of 271 ng/g, and had a slow elimination rate (t_1/2β = 14.6 hours), which suggested that berberine might directly act on certain regions of the thalamus, have pharmacological effects on some cerebral dysfunctions, and be an active ingredient of Huang Lian Jie Du Tang for the treatment of cerebral disease.

A framework for investigating information processing in cortico-thalamocortical (cortico-TC) networks is presented, that in part can be used to model and interpret individual changes in electroencephalographic spectra and event-related potentials such as those from the Brain Resource International Database. Scientific work covering neurophysiology, TC firing modes, and TC models are explored in the framework to explain how the brain might process complex information in a multistage process. It is proposed that the thalamus and the cortico-TC system have unique ionic properties and transmission delays (in humans), which are suited to the function of taking "snapshots" or samples of complex environmental stimuli, rather than continuous data streams. This leads to careful and sequential coordination of stimulus and response processes, and increases the probability of information transfer and the resulting information complexity in higher cortical regions. Given the scope of this framework, the multidimensional and standardized Brain Resource International Database provides a pertinent set of measures for both testing hypotheses generated from the model, and for fitting the model to experimental data to investigate mechanisms underlying information processing.

A prerequisite for a synthetic description of the learning and memory (LM), neural bases is a model of the brain. The model we have adopted is based on functional anatomy and consists of three interacting systems. The first, R for representation, is made of the neurons which code sensory information or motor programs with the highest precision. The second, A for activation, comprises the neurons which are most directly involved in arousal and motivation. The third system, S for supervision, controls goal-directed behaviors. The best illustration of its functions is the “voluntary act” in humans: it involves a representation of a goal and of the appropriate strategies, the evaluation of the results and the correction of errors.

The memory system is not an anatomically separate entity but a set of interactions between R, A and S. In these interactions, the three systems have different though complementary functions. R is mainly involved in encoding and storage. S plays a role in encoding and retrieval through the control of attention and cognitive strategies. Structures of A, which modulate R and S activities, are involved in all stages of memory processes. Different types of LM set into play different types of interactions between R, A and S.

Within this general scheme, we considered data from different levels of organization, from the whole brain to the molecule, through intermediates such as small networks (for example, the cortical column). Finally, an attempt is made at defining the perspectives for future research. Among its main objectives are the integration of LM bases in the neurobiology of the whole behavior, the genetic and developmental factors, new therapies for improving memory in aged and demented people, the design of formalisms able to represent large-scale neural networks.

All living systems are dependent on information from the past. While this information may in part be inherent and genetically coded, there was through evolution a steadily growing increase of flexible and individual-specific information encoding, storage, and retrieval. In mammals, and especially man, this biological tendency resulted in a largely environment-stimulated access to information most essential for survival of the individual and the species. Consequently, the remembrance of emotionally and motivationally flavored events was of greatest importance. The apparent result of this is that there is a substantial overlap of those brain structures implicated in the processing of emotional, motivational, and memory processes, a conclusion obvious from the roles attributed to the Papez circuit. How interwoven arousal, attention, mood, and affect are, can most directly be deduced from the assessment of brain damaged patients. Examples from cases with memory disturbances in whom mood and affect influence memorizing as well as some hypotheses on the possible or likely interaction of mood and memory are given.

In man, the localized thalamic lesions giving rise to memory disorders have generally a vascular origin (infarcts). They very often affect several nuclei or associated tracts, which makes the pathophysiologic interpretations more difficult. Disorders are furthermore partially regressive with time, in their severity but also in their quality, which explains why some of the classical dissociations in amnesia are only observed at the late stage. Memory disorders are variable according to the lesion site and their uni or bilateral character. The “purest” and most severe amnesia are observed in bilateral injury of the anterior or antero-internal structures, which is much more rare in unilateral ones. Severe deficits in “declarative” learning tasks and in long term memory are then observed, which predominate in free recall. Short-term memory is often deficient at the initial and secondary stages, even when late evaluation may find it to be relatively unimpaired. Retrograde amnesia is frequent, but less severe than anterograde amnesia and the temporal gradient, frequently described by the patients, is difficult to assess with the classical tests (questionnaires). These patients have important and often lasting impairment in the control of time, which would contribute to the explanation of their amnesia (source amnesia). In the case of paramedian and moreover subthalamic extension of the lesions, patients frequently have at the initial stage vigilance disorders and then attention impairment and cognitive slowing. Their short-term memory and retrograde memory disorders could be more severe. One of the other factors which may contribute to the severity of amnesia is the extension of the lesions in the more external structures, dorsomedial and lateral nuclei: patients then present supplementary cognitive disorders in language (left lesions) or treatment of spatial information (right lesions). At the late stage, a memory disorder corresponding to the main initial deficit may persist. This phenomenon, related to the hemispheric specialization, is more easily observed in unilateral lesions. Amnesia could also be more severe in the case of left thalamic injury, and this could be related to the “declarative” character of most of the tests used.