Thalamic stimulation for chronic pain

Electrical stimulation of the thalamus was found to be effective for the treatment of chronic intractable pain of various etiologies. Diencephalic recordings revealed spontaneous focal electrical discharge patterns with relatively low activation thresholds. Localization of the optimum thalamic discharge site is used as a guide for the electrode implant to be used for chronic stimulation. The thalamic sites which most frequently displayed the low threshold spontaneous focal discharge activity were the CM-Pf complex and related intralaminar nuclear structures. Generation of diencephalic pain-reverberating circuits was discussed in relation to explaining the pain syndromes herein described. The applied electrical stimulation is thought to electrophysiologically 'jam' the low threshold discharging systems and thereby alleviate pain.     

经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱干预作用的初步研究

目的:探讨经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱的干预作用。方法:研究采用自身前后对照的试验设计。16名受试者均接受2次24 h睡眠剥夺,2次睡眠剥夺间隔3周,受试者分别于第1次正常睡眠后、24 h睡眠剥夺后、经颅电刺激(真或假刺激)干预后(真、假刺激电流大小均为1 mA,电流作用时间分别为20 min、2 s,干预实验均持续20 min)及第2次经颅电刺激(假或真刺激)干预后采集静息态磁共振成像数据。以睡眠剥夺前收集静息态功能磁共振数据作为基线,选取双侧后扣带回皮质作为种子点进行全脑功能连接分析,观察睡眠剥夺前后及经颅电刺激真、假刺激后大脑的功能连接变化。结果:与正常睡眠后相比,24 h睡眠剥夺后双侧后扣带回皮质与双侧丘脑间的功能连接上升(P<0.01),与右侧楔前叶、海马旁回以及双侧岛叶间的功能下降(P<0.01)。与假刺激相比,给予真刺激后左侧后扣带回皮质与右侧楔前叶功能连接上升(P<0.01);与双侧丘脑、岛叶及右侧大脑皮质功能连接下降(P<0.01)。右侧后扣带回皮质与全脑的功能连接在双侧丘脑、右侧岛叶及大脑皮层间也存在下降(P<0....     

Effect of mediodorsal thalamic nucleus on the respiratory neurons from medulla oblongata and the rat respiration during hypoxia]

In the normal as well as in the oxygen deficiency conditions the research has been conducted to study the influence of associative mediodorsal (MD) nucleus of thalamus on impulsive activity of respiratory neurons of medulla oblongata of respiration. In conditions of normal atmospheric pressure, before the uplift of the animals, the electrical stimulation of MD of nucleus of thalamus has had mainly inhibiting influence. In the initial phase, on 4-5 thousand meter altitude, activation of frequent discharge of neurons occurred, the respiration has become frequent as well. In this situation the inhibiting influence of stimulation of MD nucleus of thalamus was more accentuated than in conditions of normoxia. In the second phase, 7.5-8 thousand meters, the opposite occurred, i.e. reduction of respiratory center activity of medulla oblongata and thalamus. In this difficult conditions of hypoxia, a reduction of impulsive activity of neurons has been observed; the respiration was becoming slower and surface. Meanwhile, the inhibiting influence of thalamus was not significant.     

c-fos Expression in Gracilothalamic Tract Neurons after Electrical Stimulation of the Injured Sciatic Nerve in the Adult Rat

The number of c-fos protein-like immunoreactive (Fos-LI) cells in the gracile nucleus was determined after electrical stimulation at Aα/Aβ-fiber strength of the normal and of the previously injured sciatic nerve in adult rats. No Fos-LI cells were seen after electrical stimulation of the noninjured sciatic nerve, or after sciatic nerve injury without electrical stimulation. However, stimulation 21 days after sciatic nerve transection resulted in numerous Fos-LI cells in the ipsilateral gracile nucleus. Combined Fos immunocytochemistry and retrograde labeling from the thalamus showed that the majority (76%; range = 70–80%) of the cells in the gracile nucleus that expressed Fos-LI after nerve injury projected to the thalamus. The results indicate that morphological, biochemical, and physiological alterations in primary sensory central endings and second-order neurons, which have earlier been demonstrated in the dorsal column nuclei after peripheral nerve injury, are accompanied by changes in the c-fos gene activation pattern after stimulation of the injured sciatic nerve. A substantial number of the c-fos-expressing neurons project to the thalamus.     

Unit responses in the cat auditory cortex to electrical stimulation of nerve fibers innervating receptor cells in different parts of the organ of corti

Responses of 200 primary auditory cortical neurons to electrical stimulation of nerve fibers in different receptor zones of the cochlea were studied in cats anesthetized with pentobarbital. Under the influence of paired stimulation, after the response to the conditioning stimulus a state of prolonged (from 4 to 200 msec) refractiveness to the second stimulus developed in all the neurons tested. This long-lasting inhibition of unit activity was due to inhibition developing in the thalamus and the auditory cortex itself. The intensity and duration of excitation and inhibition in the cortical projection focus were maximal when the center of the receptive field was stimulated and decreased when the stimulus shifted from the center to the periphery. The region of the receptor surface of the cochlea to stimulation of which the auditory cortical neurons respond by an action potential is much narrower than the region whose electrical stimulation depresses the discharge of these neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 418–425, July–August, 1982.     

Synchronization in a network of fast-spiking interneurons

Experimental results revealed that in neocortex inhibitory fast-spiking (FS) interneurons interact also by electrical synapses (gap-junctions). They receive sensory information from thalamus and transfer it to principal cells by feedforward inhibition. Moreover, their synchronous discharge enhances their inhibitory control of pyramidal neurons. By using a biophysical model of FS interneurons the synchronization properties of a network of two synaptically coupled units are investigated. In the case they interact only by inhibitory synapses, well defined regions exist in the parameters space described by the strength and duration of the synaptic current, where synchronous regimes occur. Then an empirical protocol is proposed to determine approximately the borders of the synchronization manifold (SM). When electrical synapses are included, the region of synchronous discharge of the two interneurons becomes larger. In both cases, the coherent states are characterized by discharge frequencies in the gamma range. Lastly, the effects of heterogeneity, either obtained by using different stimulation currents or unidirectional inhibitory coupling, are studied.     

The electrophysiological characteristics and behavioral manifestations of hippocampal and thalamic spreading depression]

Behavioral manifestations of spreading depression (SD) were compared with SD electrophysiological characteristics in these structures. Carbon electrodes were suitable for recording DC slow potential changes in freely moving animal. It was shown that short (0.1 s) high-frequency (200 Hz) electrical stimulation of thalamus and hippocampus with intensity 50-300 microA easily triggered SD wave in these structures in narcotized and awake rats. The threshold of SD occurrence in dorsal hippocampus was the same or sometimes lower than that of the primary afterdischarge. Penetrating SD into ventral hippocampus provoked long latency seizure discharge and wet-dog shakings in awake rats. Intensity of locomotor activity accompanying bilateral hippocampal SD exceeded orienting response significantly. Contrary to hippocampus, thalamic SD was usually subseizure and unilateral phenomenon and had a clear tranquil effect on the rat locomotor activity. It was found that the rats didn't change the compartment preference after 20-45 SD waves in the thalamus or in the hippocampus.     

The relationship between vigilance and cortical EEG manifestations after electrical stimulation of the thalamus and hippocampus in unrestrained rats.

The thalamus or hippocampus of unanaesthetized rats with impaired cortical and subcortical electrodes was stimulated with rhythmic series of electrical pulses of 3--15/sec frequency. In both cases, stimulation either did not affect vigilance, or led to a higher degree of wakefulness. The incidence of recruiting responses (RR) and of self-sustained afterdischarges (SSAD) evoked by stimulation of the thalamus was not correlated to the preceding state of vigilance. In stimulation of the hippocampus, a significantly higher incidence of SSAD was found in the quiet waking state. The correlation between the elicitation of RR and SSAD was also significantly the highest after stimulation of the hippocampus during wakefulness.     

Rhythmic after-discharge in the cat cerebral cortex and deep brain structures during stimulation of the claustrum

Effects of stimulation of the claustrum and caudate nucleus in the neocortex and various deep brain structures were studied in acute experiments on unanesthetized cats immobilized with tubocurarine. A rhythmic after discharge appeared in neocortical areas 4–7 and 18 (according to Reinoso-Suarez' atlas), and also in the caudate nucleus and various parts of the thalamus. A similar discharge also was observed in the claustrum itself. Diencephalic brain section at the level of the ventral anterior nucleus weakened but did not completely abolish the cortical rhythmic after-discharge in the anterior regions of the neocortex evoked by stimulation of the claustrum. This discharge was completely blocked after sagittal brain section between the claustrum and the rest of the thalamus.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 15, No. 2, pp. 121–127, March–April, 1983.     

Electrophysiological relations between the superior colliculus and the red nucleus in the cat.

The electrical activity of single units located in the parvicellular part of the red nucleus (pRP) was recorded extracellularly in nitrous oxide anesthetized and C1-transected adult cats. In this area, neurons were found to respond to electrical stimulation applied to intermediate and deep layers of the right superior colliculus (SC). Forty neurons located in the pRN of both sides were studied. Three neurons out of 18 (16.6%) located in the contralateral pRN and six neurons out of 22 (27.3%) located in the ipsilateral pRN were driven by the right SC stimulation. The pRN neurons were separated into four groups according to the latency response to the SC stimulation: 1) 0.6-1.9 ms, 2) 2-4 ms, 3) 4-6 ms, 4) variable latency responses. Each of these four groups of neurons showed a particular pattern of discharge, even though their discharge frequency showed a strong consistency. Four pRN neurons, which responded to SC stimulation, showed a significant correlation with spontaneous horizontal eye movements of saccadic type. It is known that the SC represents one of the main outputs of the striato-nigral motor system. The relation between the SC and the pRN described in the present study suggest that connections exist between the cortico-rubral and the striato-nigral systems, since both have the SC as a common output structure. It is likely, therefore, that the cortico-rubral-SC system is involved in the control of oculomotor functions, and that the SC may serve to establish interactions between systems concerned with eye movements.     

Effect of dorsal column stimulation on pain-induced intracerebral impulse patterns.

Evoked electrical potentials were recorded via intracerebral electrodes in a patient with stump and phantom limb pain who had a previously implanted dorsal column stimulator. When pain was elicited by peripheral stimulation it was found that positive deflections appeared in the ventrolateral nucleus of the thalamus at time latencies corresponding to the propagation velocities of A delta- and C-fibres. Dorsal column stimulation completely eliminated the C-fibres. Dorsal column stimulation completely eliminated the C-fibre deflection and partially eliminated the A delta-fibre deflection.     

Stimulation of the hippocampus and its effect on electrographic manifestations of the brain in unrestrained rats.

The dorsal hippocampus was electrically stimulated in unanaesthetized, unrestrained rats with a cobalt-gelatin rod in their cortex. The significance of the hippocampus in the elicitation of both physiological spontaneous rhythmic activity (episodic activity of 8--9/sec frequency bound, in rats, to a state of quiet wakefulness, and "sleep spindles") and pathological rhythmic activity of the self-sustained after-discharge (SSAD) type was determined from the aspect of the EEG and behavioural characteristics. 1. Single electrical pulses (0.1 msec, 1--10 V, 0.3/sec) elicited an evoked potential bilaterally in the somatosensory cortex. Elicitation of rhythmic after-activity (of the type of episodes or sleep spindles) was observed only in some cases in which an adequately strong stimulus was used. 2. Repeated series of rhythmic electrical stimuli following each other at short intervals (2--3 min) led to the formation of SSAD in about one third of the cases and at all stimulation frequencies (3-15/sec), although low frequencies (3--4/sec) were the least effective. The character of the SSAD and simultaneous behavioural phenomena differed fundamentally from those evoked by electrical stimulation of the thalamus (Chocholová et al. 1977). The development of paroxysmal after-activity was signalled by responses of a more or less distinct "recruiting" character during stimulation. On the basis of a comparison of electrographic and behavioural manifestations after electrical stimulation of the thalamus and hippocampus, the possibility of both thalamic and extrathalamic projection from the hippocampus to the cortical region is considered.     

Influence of descending forebrain projections on processing of acoustic signals and audiomotor integration in the anuran midbrain

We tested the role of descending projections for auditory processing and audiomotor integration in the anuran torus semicircularis. Intracellular recordings were made from isolated brain preparations, impaled neurons were stained. Auditory neurons responded to electrical stimulation of striatum and/or dorsal thalamus, they integrated forebrain and auditory nerve inputs. High frequency stimulation in striatum or thalamus changed the auditory response of torus neurons located in the laminar subnucleus. Our results suggest that the laminar nucleus is the primary target of forebrain projections, which provides a basis for modulation of acoustically guided behaviour.     

Real-Time Monitoring of Electrically Stimulated Norepinephrine Release in Rat Thalamus: II. Modeling of Release and Reuptake Characteristics of Stimulated Norepinephrine Overflow

Abstract: As in the preceding study, electrical stimulation was used to effect release overflow of norepinephrine in the rat thalamus. Using a weak electrochemical pretreatment of a carbon fiber electrode, it was possible to "tune in" the electrochemical response signal for norepinephrine without metabolite interference. This reasonably selective signal was then used to study the degradation of norepinephrine release ability caused by prolonged stimulation. Further, the signals were modeled by the method used successfully for stimulated dopamine overflow, providing hitherto unavailable information on the temporal and spatial characteristics of norepinephrine release overflow. Pertinent comparisons between the release characteristics of the dopamine and norepinephrine systems show that the half-life for norepinephrine in the extracellular fluid space is ∼1 s in thalamus compared with 33 ms for dopamine in caudate.     

Activation of thalamic ventroposteriolateral neurons by phrenic nerve afferents in cats and rats.

It has been demonstrated that phrenic nerve afferents project to somatosensory cortex, yet the sensory pathways are still poorly understood. This study investigated the neural responses in the thalamic ventroposteriolateral (VPL) nucleus after phrenic afferent stimulation in cats and rats. Activation of VPL neurons was observed after electrical stimulation of the contralateral phrenic nerve. Direct mechanical stimulation of the diaphragm also elicited increased activity in the same VPL neurons that were activated by electrical stimulation of the phrenic nerve. Some VPL neurons responded to both phrenic afferent stimulation and shoulder probing. In rats, VPL neurons activated by inspiratory occlusion also responded to stimulation on phrenic afferents. These results demonstrate that phrenic afferents can reach the VPL thalamus under physiological conditions and support the hypothesis that the thalamic VPL nucleus functions as a relay for the conduction of proprioceptive information from the diaphragm to the contralateral somatosensory cortex.     

研究报告: 大鼠感觉运动系统静息态脑网络研究

为了理解啮齿类动物的脑功能连接,本文利用9.4T fMRI获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数．结果发现：给予前爪电刺激时,刺激对侧初级感觉皮层(S1)、丘脑(Tha)有较强的正激活,双侧尾状壳核(CPu)有较强的负激活．静息状态时大鼠感觉/运动皮层内部、丘脑内部的连接性较强,而感觉/运动皮层与丘脑之间的连接较弱,双侧感觉运动系统之间存在较强的同步低频振荡,感觉运动系统在静息态时的脑网络具有小世界属性．结果提示,啮齿类动物在大脑信息处理中的功能分离和整合可能与人类存在某些相似性,支持哺乳动物中枢神经系统的基本功能存在遗传保守性的观点．     

剌激兔面神经核背内侧区对孤束核腹外侧亚核呼吸相关神元的影响

In urethane-anesthetized, vagotomized and paralyzed rabbits, effects of electrical stimulation of the dorso-medial area of the nucleus facialis (DMNF) on the respiration-related units (RRUs) in ventro-lateral region of nucleus tractus solitaris (VLNTS) were observed. The experimental results showed that during electrical stimulation of DMNF the majority of the inspiratory (I) neurons (64.4%) were increased in frequency and duration of discharge, some to a marked extent. During electrical stimulation of DMNF the expiratory neurons (35%) were decreased in their frequency and duration of discharge, some to a marked extent too. The responses of RRUs in ipsilateral and contralateral VLNTS to stimulation of DMNF was not statistically significant (P greater than 0.05). It is suggested that DMNF may have a facilitating effect on the inspiratory neurons and an inhibiting effect on the expiratory neurons in VLNTS.     

电刺激大鼠脊神经皮支对远距离机械感受单位电活动的影响

实验采用分离神经细束的方法,观察逆行电刺激大鼠脊神经背侧皮支后,在相距较远的神经细束上记录到的Aδ和C类机械感受单位电活动的变化。刺激T9脊神经背侧皮支,在T12神经细束上记录到59.3%（16/27）的Aδ和71.2%(37/52）的C类单位在刺激后90～120s放电显著增加。刺激T8脊神经背侧皮支,在T12神经细束上记录到47.8%(11/23）的Aδ单位和36.6%(15/41）的C类单位在刺激后120～150s放电显著增加。大多数单位（18/23）的机械感受阈值在电刺激远距离脊神经背侧皮支后降低。结果表明,逆行电刺激外周感觉神经,可以使相距较远的Aδ和C类机械感受单位致敏,其传入放电增加。     

A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI]

BACKGROUND: Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-controlled) transcutaneous VNS (tVNS) at the inner side of the tragus. This paper shows the feasibility of these and their potential for brainstem and cerebral activations as measured by blood oxygenation level dependent functional MRI (BOLD fMRI). MATERIALS AND METHODS: In total, four healthy male adults were scanned inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. We ensured that our newly developed tVNS stimulator was adapted to be an MR-safe stimulation device. In the experiment, cortical and brainstem representations during tVNS were compared to a baseline. RESULTS: A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left locus coeruleus, the thalamus (left > right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula. Deactivations were found in the right nucleus accumbens and the right cerebellar hemisphere. CONCLUSION: The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP are discussed and new possibilities of tVNS are hypothesised.     

Fictive cough in the cat.

Experiments were performed to determine whether cough could be elicited in paralyzed cats ventilated on a respiratory cycle-triggered pump. Midcollicular decerebrate cats were paralyzed and artificially ventilated on a phrenic-triggered pump. Phrenic and cranial iliohypogastric nerve efferent activities were recorded. Cough was elicited by electrical stimulation of the superior laryngeal nerve (SLN) or probing the intrathoracic trachea. Fictive coughs induced by electrical stimulation of the SLN or mechanical stimulation of the intrathoracic trachea consisted of large-amplitude bursts in phrenic discharge immediately followed by large bursts in cranial iliohypogastric discharge. During fictive cough, phrenic postinspiratory discharge was reduced relative to control cycles. Codeine (0.03-1 mg/kg iv) decreased both SLN- and probe-induced fictive cough. I conclude that fictive cough can be produced in paralyzed cats ventilated on a phrenic-triggered pump. Furthermore, fictive cough can be produced in the absence of afferent feedback associated with active expiration.