Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain.

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.

A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.

Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.

The effect of amygdala kindling on neuronal firing patterns in the lateral thalamus in the GAERS model of absence epilepsy.

OBJECTIVE: The co-occurrence of absence and mesial temporal lobe epilepsy is rare in both humans and animal models. Consistent with this, rat models of absence epilepsy, including genetic absence epilepsy rats from Strasbourg (GAERS), are resistant to experimental temporal lobe epileptogenesis, in particular by amygdala kindling. Structures within the cortical-thalamocortical system are critically involved in the generation and maintenance of the electrographic spike-and-wave discharges (SWDs) that characterize absence seizures. Using in vivo electrophysiologic recordings, this study investigated the role of thalamocortical circuitry in the generalization of amygdala-kindling induced seizures in the GAERS and the nonepileptic control (NEC) strain of Wistar rats. METHODS: GAERS and NEC rats were implanted with a stimulating electrode in amygdala and stimulated at afterdischarge threshold twice daily to a maximum number of 30 stimulations. Thereafter extracellular single neuron recordings were performed in vivo under neuroleptanesthesia in the thalamocortical network. RESULTS: In NEC rats, amygdala kindling induced convulsive class V seizures and altered characteristics of neuronal activity in the thalamic reticular nucleus (TRN), in particular decreased firing rates and increased burst firing patterns. Less marked changes were seen in other regions examined: the ventroposteromedial nucleus of thalamus (VPM), the CA3 region of the hippocampus, and the deep layers (V/VI) of the cortex. GAERS did not progress beyond class II seizures, with a matched number of kindling stimulations, and the thalamic neuronal firing alterations observed in NEC rats were not seen. SIGNIFICANCE: These data suggest that the TRN plays an important role in kindling resistance in GAERS and is central to the control of secondary generalization of limbic seizures.

Reorganization of the connectivity of cortical field DZ in congenitally deaf cat.

Psychophysics and brain imaging studies in deaf patients have revealed a functional crossmodal reorganization that affects the remaining sensory modalities. Similarly, the congenital deaf cat (CDC) shows supra-normal visual skills that are supported by specific auditory fields (DZ-dorsal zone and P-posterior auditory cortex) but not the primary auditory cortex (A1). To assess the functional reorganization observed in deafness we analyzed the connectivity pattern of the auditory cortex by means of injections of anatomical tracers in DZ and A1 in both congenital deaf and normally hearing cats. A quantitative analysis of the distribution of the projecting neurons revealed the presence of non-auditory inputs to both A1 and DZ of the CDC which were not observed in the hearing cats. Firstly, some visual (areas 19/20) and somatosensory (SIV) areas were projecting toward DZ of the CDC but not in the control. Secondly, A1 of the deaf cat received a weak projection from the visual lateral posterior nuclei (LP). Most of these abnormal projections to A1 and DZ represent only a small fraction of the normal inputs to these areas. In addition, most of the afferents to DZ and A1 appeared normal in terms of areal specificity and strength of projection, with preserved but smeared nucleotopic gradient of A1 in CDCs. In conclusion, while the abnormal projections revealed in the CDC can participate in the crossmodal compensatory mechanisms, the observation of a limited reorganization of the connectivity pattern of the CDC implies that functional reorganization in congenital deafness is further supported also by normal cortico-cortical connectivity.

Núcleos intralaminares posteriores del tálamo y procesos cognitivos / Posterior intralaminar nuclei of the thalamus and cognitive processes

Introducción. El núcleo parafascicular en las ratas y el complejo centromediano parafascicular en los primates y otros mamíferos constituyen los llamados núcleos intralaminares posteriores (ILp) del tálamo. Al igual que el sistema reticular activador ascendente y el de los ganglios basales-tálamo-cortical, los núcleos ILp forman parte de los sistemas de arousal cerebral. Objetivo. Describir y analizar diferentes investigaciones experimentales con animales y trabajos clínicos en humanos que sugieren que los núcleos ILp podrían formar parte de un sustrato neurofisiológico subcortical relacionado con los procesos de atención, aprendizaje y memoria. Desarrollo. Los estudios de lesión del núcleo parafascicular en ratas y neuropatológicos y de neuroimagen en humanos muestran una relación entre la degeneración de las neuronas de los núcleos ILp y el déficit cognitivo que se observa en diversas tareas de aprendizaje y memoria en animales, en diferentes enfermedades neurológicas y en alteraciones de los estados de consciencia. Conclusiones. Por sus características neuroanatómicas y neurofisiológicas y sus implicaciones funcionales, los núcleos ILp son excelentes candidatos para la investigación de los procesos cognitivos en el ámbito básico de la psicobiología y el clínico de la neurología (AU)

Introduction. The parafascicular nucleus in rats and the centromedian parafascicular complex in primates and other mammals are the so-called posterior intralaminar nuclei (pIL) of the thalamus. Like the ascending reticular activating system and the basal ganglia-thalamocortical circuit, the pIL nuclei are part of the brain arousal systems. Aim. To describe and analyze different animal and human studies suggesting that the pIL could also be part of a neurophysiological subcortical system related to cognitive processes as attention, learning and memory. Development. Both parafascicular nucleus lesion studies in rats and neuropathological and neuroimaging reports in humans, indicate a relationship between the degeneration of pIL neurons and the cognitive deficits observed in learning and memory tasks in animals and also in several human neurological diseases and in consciousness disorders. Conclusions. Considering its neuroanatomical, neurophysiological and functional characteristics, the pIL can be considered excellent candidates for investigating cognitive processes in the field of psychobiology and clinical neurology (AU)

Spontaneous low threshold spike bursting in awake humans is different in different lateral thalamic nuclei.

Spontaneous action potential bursts associated with low threshold calcium spikes (LTS) occur in multiple human lateral thalamic nuclei, each with different physiologic characteristics. We now test the hypothesis that different patterns of spontaneous LTS bursting occur in these nuclei during awake surgery in patients with essential tremor and the arm at rest. This protocol was chosen to minimize the effect of the patient's disease upon thalamic activity which is a potential confound in a surgical study of this type. Neuronal activity was studied in the human thalamic nuclei receiving somatic sensory input (Vc, ventral caudal), input from the deep cerebellar nuclei (Vim, ventral intermediate), or input from the pallidum (Vo, ventral oral). In each nucleus the burst rates were significantly greater than zero. Burst rates were higher in Vc than in Vim, while firing rates were lower. These findings suggest that neurons in Vc are hyperpolarized and have more frequent inhibitory events. Pre-burst inter-spike intervals (ISIs) were significantly longer in Vc, but were significantly shorter when corrected for the average ISIs between bursts (burst rate/inverse of the primary event rate). These results suggest that inhibitory events in Vc are of lower magnitude relative to a hyperpolarized resting membrane potential. Studies in many species demonstrate that input from the pallidum to the thalamus is inhibitory, suggesting that input to Vo is predominantly inhibitory. However, neurons in Vo have neither slower firing rates nor more frequent LTS bursts. Previous studies have found that spontaneous LTS is similar between classes of neurons within Vc, as defined by their response to thermal and painful stimuli. The differences in spontaneous LTS between human nuclei but not between functional classes within a nucleus may be a basic organizing principle of thalamic inhibitory circuitry.

[Deficit in risk-taking decision-making of patients with lesions of prefrontal cortex].

OBJECTIVE: To investigate the influence of injury of prefrontal cortex on the risk-taking decision-making and to test the hypothesis that the orbitofrontal area is involved in the special network of risk-taking decision-making. METHODS: 47 patients with lesions in the prefrontal lobe, 21 in the orbitofrontal area (OBF) and 19 in the dorsolateral prefrontal cortex (DLF), and 40 healthy controls (HC group) were administered with a risk-taking task. RESULTS: The risky response rate after punishment of the HC group was 0.54 +/- 0.23, significantly fewer than before punishment (t = -3.82, P < 0.01), and the risky response rate after punishment of the DLF injury group was 0.68 +/- 0.16, significantly fewer than before punishment too (t = -2.32, P < 0.05). The risky response rate after reward of the patients with lesions in OBF areas was 0.79 +/- 0.19, significantly higher than that of the HC group (0.68 +/- 0.16, P < 0.05), and the risky response rate after punishment of the patients with lesions in OBF areas was 0.82 +/- 0.18, significantly higher than that of the HC group (0.54 +/- 0.23, P < 0.05). The risky response rates after reward and after punishment of the DLP group were 0.72 +/- 0.22 and 0.63 +/- 0.25 respectively, both not significantly different from those of the HC group (both P > 0.05). CONCLUSION: The patients with lesions in the orbitofrontal area, not in the dorsolateral prefrontal cortex, have a specific deficit in risk-taking decision-making, i.e. an inhibition effect of punishment, reduced sensitivity to punishment but increased sensitivity to reward. The orbitofrontal areas play an important role in risk-taking decision-making processes.

The lateral ventromedial thalamic nucleus spreads nociceptive signals from the whole body surface to layer I of the frontal cortex.

Neurons within the lateral ventromedial thalamic nucleus (VMl) convey selectively nociceptive information from all parts of the body. The present experiments were performed in rats and were designed to determine the organization of cortical projections from VMl neurons. In a first series of experiments, these cells were characterized electrophysiologically and individually labelled in a Golgi-like manner following juxtacellular electrophoresis of biotin-dextran. In a second experimental series, topical applications of the tracers fluorogold and tetramethylrhodamine-labelled dextran were placed into both the rostral-most and caudal areas of layer I of the dorsolateral frontal cortex, respectively. All VMl nociceptive neurons were fusiform and their full dendritic arborizations were bipolar, extending in the lateromedial axis. VMl cells are thus particularly well located to receive widespread nociceptive inputs via a brainstem link, viz. the medullary subnucleus reticularis dorsalis. VMl neurons driven by 'whole body' nociceptive receptive fields project to the rostral part of the layer I of the dorsolateral frontal cortex. These projections are widespread because double-labelling data showed a great number of VMl neurons labelled from both rostral and caudal dorsolateral cortices. The VMl comprises a homogeneous, organized subset of thalamic neurons that allow any signals of pain to modify cortical activity in a widespread manner, by interacting with the entire layer I of the dorsolateral neocortex.

Bilateral pallidal stimulation for idiopathic segmental axial dystonia advanced from Meige syndrome refractory to bilateral thalamotomy.

Meige syndrome is an adult-onset dystonic movement disorder that predominantly involves facial muscles, while some patients with this syndrome develop spasmodic dysphonia and dystonia of the neck, trunk, arms, and legs. We report that all dystonic symptoms that had been refractory to both pharmacotherapy and bilateral thalamotomy were markedly alleviated by bilateral pallidal stimulation in a patient with segmental axial dystonia advanced from Meige syndrome.