Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease

Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive. VIM stimulation strongly decreased the tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateral extrapyramidal movement disorders.     

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.     

Inhibition of nociceptive neurons by internal capsule stimulation

The mechanism of pain relief by internal capsule (IC) stimulation was investigated in 32 adult cats. Nociceptive neuronal activity of the nucleus ventralis posteromedialis (VPM), responding to contralateral pulp stimulation, was suppressed by IC stimulation to a greater extent than activity in the posterior nuclear group (PO) or centre-median nucleus. On the contrary, suppression of neuronal firing by intraventricular morphine-HCl predominated in PO neurons. These results suggest that pain relief by IC stimulation may be mediated through inhibitory effects on nociceptive neurons of the thalamic sensory relay nuclei.     

Plastic change of thalamic organization in patients with tremor after stroke

Thirteen patients with tremor after stroke were treated by stereotactic thalamotomy. Prior to making therapeutic lesions, microrecordings were tried and the findings were compared with our own results obtained in Parkinson's disease. Several characteristic features were revealed in terms of changes in electrical activity in and around the thalamic Vim nucleus. These findings support the idea that reorganization of the thalamic sensory nuclei might take place.     

Unit responses of the first and second somatosensory cortical areas to peripheral,thalamic, and cortical stimulation

Unit responses of the first (SI) somatosensory area of the cortex to stimulation of the second somatosensory area (SII), the ventral posterior thalamic nucleus, and the contralateral forelimb, and also unit responses in SII evoked by stimulation of SI, the ventral posterior thalamic nucleus, and the contralateral forelimb were investigated in experiments on cats immobilized with D-tubocurarine or Myo-Relaxin (succinylcholine). The results showed a substantially higher percentage of neurons in SII than in SI which responded to an afferent stimulus by excitation brought about through two or more synaptic relays in the cortex. In response to cortical stimulation antidromic and orthodromic responses appeared in SI and SII neurons, confirming the presence of two-way cortico-cortical connections. In both SI and SII intracellular recording revealed in most cases PSPs of similar character and intensity, evoked by stimulation of the cortex and nucleus in the same neuron. Latent periods of orthodromic spike responses to stimulation of nucleus and cortex in 50.5% of SI neurons and 37.1% of SII neurons differed by less than 1.0 msec. In 19.6% of SI and 41.4% of SII neurons the latent period of response to cortical stimulation was 1.6–4.7 msec shorter than the latent period of the response evoked in the same neuron by stimulation of the nucleus. It is concluded from these results that impulses from SI play an important role in the afferent activation of SII neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 351–357, July–August, 1976.     

Reorganization of the vestibular-thalamic projections following injury of the cerebellar interpositus and deiters vestibuar nuclei

Plastic reorganization of the vestibular-thalamic system was studied in adult cats. It was shown, that preliminary (3 months before) injury of the cerebellar contralateral nucleus interpositus or lateral vestibular nucleus of Deiters leads to reorganization of vestibular-thalamic projections. Ipsilateral projections to the ventrolateral nucleus of thalamus arised from vestibular nuclear complex since the pattern of normal representations to mentioned thalamic nucleus were changed. The peculiarities of distribution and morphological structure of vestibular neurons forming new projections to the ventrolateral thalamic nucleus were studied as well.     

Analysis of conduction of visual,somatic, and audiovibratory sensory information to the hippocamapal cortex in lizards

Acute electrophysiological experiments on lizards (Ophisaurus apodus) showed that electrical stimulation of the anterior dorsolateral thalamic nucleus and medial forebrain bundle evokes short-latency responses in the hippocampal (mediodorsal) cortex which coincides in distribution and configuration with responses in the same cortical area to sensory stimulation. Extensive destruction of these structures inhibits, or even completely blocks, the conduction of sensory (visual, somatic, audiovibratory) and tactile impulses to the hippocampal cortex. It is concluded that the anterior dorsolateral thalamic nucleus and medial forebrain bundle constitutes, if not the only, at least the principal pathway for transmission of these sensory impulses to the hippocampal cortex in lizards.     

Emotional memory and psychopathology.

A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of the neural system mediating this form of learning. The pathways involve transmission of sensory information from processing areas in the thalamus and cortex to the amygdala. The amygdala''s lateral nucleus receives and integrates the sensory inputs from the thalamic and cortical areas, and the central nucleus provides the interface with motor systems controlling specific fear responses in various modalities (behavioural, autonomic, endocrine). Internal connections within the amygdala allow the lateral and central nuclei to communicate. Recent studies have begun to identify some sites of plasticity in the circuitry and the cellular mechanisms involved in fear conditioning. Through studies of fear conditioning, our understanding of emotional memory is being taken to the level of cells and synapses in the brain. Advances in understanding emotional memory hold out the possibility that emotional disorders may be better defined and treatment improved.     

Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons

Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2–20?Hz). Stimulus trains also resulted in significant synaptic depression above 10?Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.     

Regional differences in mechanisms of cerebral circulatory response to neuronal activation

Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF.     

The interaction of the somatosensory evoked potentials to simultaneous finger stimuli in the human central nervous system. A study using direct recordings

In order to investigate the interaction of sensory electrophysiologic fields arising from the adjacent second (II) and third (III) fingers and the distant second and fifth (V) fingers, direct recordings of somatosensory evoked potentials (SEPs) were performed from the sensory and motor cortices, the sensory thalamic nucleus (nucleus ventralis caudalis, VC) and the cuneate nucleus in humans during neurosurgical operations. Electrical stimulation was given to the II, III or V fingers individually, and also to pairs of either the II and III fingers or the II and V fingers simultaneously. The interaction ratio OR) was devised as the ratio of amplitude attenuation caused by the simultaneous stimulation to two fingers compared with the amplitude of the arithmetically summed SEPs to the individual stimulation of two fingers. The IRs were calculated on N20 and P25 from the sensory cortex, P22 from the motor cortex, P17_thal from the VC, and N16_cune and P35_cune from the cuneate nucleus.With both stimulations to the II and III fingers and the II and V fingers, P25 showed the greatest IR, followed by P22, then by P17_thal while N16_cune exhibited the smallest IR. N20 and P35_cune showed similar IRs and significantly greater IRs with II and III finger stimulation compared with II and V finger stimulation.These results thus indicate that the interaction of somatosensory impulses occurs in several structures along the sensory pathway in CNS, including the cuneate nucleus, the sensory thalamic nucleus, as well as sensory and motor cortices, with the greatest IRs in the cerebral cortices and the weakest ones in the brain-stem. They also suggest that the receptive fields of the fingers in the cortical area generating N20 are arranged according to the order of the fingers while those in the generating sites for cortical P25 and P22, thalamic P17_thal and cuneate N16_cune tend to be arranged in clusters, while P35_cune is possibly modulated by the somatosensory cortex through a long-loop feedback pathway.     

Chondroitin sulfate proteoglycans in the rat thalamus: expression during postnatal development and correlation with calcium-binding proteins in adults

Postnatal expression of chondroitin sulfate proteoglycans was studied in the rat thalamus by immunocytochemistry and Western immunoblotting techniques with monoclonal antibodies that recognize carbohydrate epitopes (clones CS-56, 1-B-5, 2-B-6). The complex of the results shows that these antibodies recognize mostly nonoverlapping molecules whose expression is regulated during postnatal development. Chondroitin sulfate proteoglycans, recognized by antibody CS-56, and hyaluronan, identified by antibody 1-B-5 after hyaluronidase digestion, are abundant in the neuropil of most thalamic nuclei at the perinatal stage and progressively decrease during the second week of life, attaining levels barely detectable by immunocytochemistry at the end of the third week. In adult thalamus, chondroitin sulfate proteoglycans of high molecular mass, bearing glycosaminoglycans unsulfated in the linking region, and recognized by antibody 1-B-5 are confined to perineuronal nets around neurons chiefly localized in thalamic reticular nucleus. The immunoreactvity for antibody 2-B-6, specific for chondroitin-4-sulfate, is low at the perinatal stage and is not detectable in adult thalamus. Double-immunolabeling has shown that, along the rostrocaudal extension of reticular nucleus, the most developed perineuronal nets are associated with a subset of neurons expressing calretinin, and not with parvalbumin-positive neurons, which represent the largest neuronal population of the nucleus. The distribution of perineuronal nets supports the presence, in thalamic reticular nucleus, of neuronal subpopulations with different morphological and physiological features.     

Calcium-Binding Proteins in the Turtle Thalamus. Analysis in the Light of Hypothesis of the “Core-Matrix” Thalamic Organization in Relation to the Problem of Homology of Thalamic Nuclei among Amniotes

Distribution of immunoreactivity (IR) to Ca-binding proteins (CaBPr) (calbindin, Calb, parvalbumin, Parv., and calretinin, Calr) was studied in the thalamus of the Central Asian terrestrial turtles (Testudo horsfieldi) and fresh water turtles (Emys orbicularis). There has been established a wide spread of these proteins, which combines overlapping and a relative alternation of distribution of different CaBPr in individual nuclei. A comparison of IR was made in two relay nuclei of the visual system, GLd and Rot. Both nuclei had IR to all CaBPr, but with different degree of intensity. In the terrestrial turtles, the amounts of Calb-, Parv-, and Calr-IR neurons in the cellular plate of the GLd were close. In this plate and in the neuropil part of this nucleus there was observed CaBPr-innervation of various density. Calr-IR neurons in the GLd of the fresh water turtles dominated over Parv- and Calb-IR neurons, whose detection varied significantly. In Rot, a clear predominance of Calb-IR neurons was shown over Parv- and Calr-IR cells by constancy of their detection, the number (1.5–2-fold higher), and intensity of the immune label, as well as the highest density of Calb and Parv innervation. The character of IR in the Rot was similar in the both turtle species. In the auditory and somatic relay thalamic nuclei and in the non-sensory anterior thalamic nuclei (Dma, Dla) there were present neurons and terminals with IR to all CaBPr without any predominance of Parv-IR in the relay nuclei and Calb-IR in the anterior thalamic nuclei. The constant and characteristic feature of Enta in the turtles of both species is a dense population of Parv-IR neurons, whose topography and cellular composition coincide with those of population of GABA-IR neurons in this nucleus. The data obtained have shown that the alternative presence of different CaBPr in the relay sensory and non-sensory thalamic nuclei, which has been established as a characteristic feature of the mammalian thalamus, is not characteristic at all of turtles. It seems that in the course of evolution there occurred a reorganization of distribution of different CaBPr in thalamic nuclei of amniotes due to changes of their functional loading. The reptilian thalamic sensory relay nuclei are likely to be represented mainly by less specific parts comparable with Calb-IR matrix of specific nuclei in the higher amniotes (mammals), while their more specialized (core) Parv-IR regions are formed later in evolution. Therefore, the distribution of Parv- and Calb-IR neurons in the turtle thalamic nuclei cannot be a criterion at evaluation of homology of thalamic nuclei in amniotes, but permits judging about the degree of their specialization.     

Somatosensory cortical unit responses in the waking cat to afferent stimuli

Extracellular and intracellular responses of 183 neurons in the primary projection area of the somatosensory cortex to electrical and tactile stimulation of the skin on the contralateral fore limb and to stimulation of the ventro-posterolateral thalamic nucleus of the ipsilateral hemisphere were studied in chronic experiments on cats. Spike responses to afferent stimuli are subdivided into three types: initial with a latent period of under 60 msec; initial followed by late responses with a latent period of over 60 msec; late with a latent period of over 60 msec. In addition another group of neurons responding to peripheral stimuli in the interval between the initial and the late response was identified. In nearly all cases the initial responses to peripheral stimulation had the form of a series of spikes, unlike responses to thalamic stimulation. It is concluded from the durations of the latent periods of these responses that about 70% of neurons in the primary projection area are activated mono- and disynaptically in response to peripheral stimulation; consequently, the intracortical spread of excitation in this zone is restricted.     

A horseradish peroxidase study on the mammillothalamic tract in the rat

The mammillary projections to the anterior thalamic nuclei were investigated in the rat, using the horseradish peroxidase (HRP) method. Pars centralis of the medial mammillary nucleus projects to the medial portion of the ateromedial nucleus (AM). Pars medialis (Mm) of the medial mammillary nucleus sends fibers to the ipsilateral AM and sparsely to the medial portion of the contralateral side. The ventral and dorsal portions of Mm project to the anterior and posterior portions of AM, respectively. The pars latralis (Ml) and pars posterior (Mp) of the medial mammillary nucleus send fibers predominantly to the ipsilateral anteroventral nucleus and sparsely to the contralateral side. A slight difference between Ml and Mp projections was observed. The lateral mammillary nucleus projects bilaterally to the anterodorsal nucleus.     

Reciprocal connections between the red nucleus and the trigeminal nuclei: a retrograde and anterograde tracing study.

An anterograde biocytin and a retrograde WGA-colloidal gold study in the rat can provide information about reciprocal communication pathways between the red nucleus and the trigeminal sensory complex. No terminals were found within the trigeminal motor nucleus, in contrast with the facial motor nucleus. A dense terminal field was observed in the parvicellular reticular formation ventrally to the trigeminal motor nucleus. The parvicellular area may be important for the control of jaw movements by rubrotrigeminal inputs. On the other hand, the contralateral rostral parvicellular part of the red nucleus receives terminals from the same zone in the rostral part of the trigeminal sensory complex, where retrogradely labelled neurones were found after tracer injections into the red nucleus. Such relationships could be part of a control loop for somatosensory information from the orofacial area.     

Primary Vagal Projection to the Contralateral Non-NTS Region in the Embryonic Chick Brainstem Revealed by Optical Recording

Using multiple-site optical recording with the voltage-sensitive dye, NK2761, we found that vagus nerve stimulation in the embryonic chick brainstem elicits postsynaptic responses in an undefined region on the contralateral side. The characteristics of the contralateral optical signals suggested that they correspond to the monosynaptic response that is related to the vagal afferent fibers. The location of the contralateral response was different from the vagal motor nucleus (the dorsal motor nucleus of the vagus nerve) and sensory nucleus (the nucleus of the tractus solitarius), and other brainstem nuclei that receive primary vagal projection. These results show that the vagus nerve innervates and makes functional synaptic connections in a previously unreported region of the brainstem, and suggest that sensory information processing mediated by the vagus nerve is more complex than expected.     

Single units activities in ventral posterior and posterior group thalamic nuclei during nociceptive and non nociceptive stimulations in the cat.

The purpose of this study was to define, in hyperventilated and unanesthetized cats, the role of the posterior thalamic nuclei in pain mechanisms. Unit activities of these structures were compared to those of the ventro-posterior nucleus during non-noxious (touch, brushing) and noxious stimulations (pinches and intra-arterial injections of bradykinin into the limbs). 135 cells with somatic inputs and clear peripheral excitatory receptive field were studied. The cells driven by noxious stimulations were located in the posterior group nuclei as anatomically defined by Rinvik. These units, preferentially excited from contralateral receptive fields, were localized in POm, POl, suprageniculate nuclei, the magnocellular division of the medial geniculate body (Mgmc) and the ventral part of the lateral posterior nucleus. At this level two groups of units were found: those driven only by noxious stimulations and those driven by both noxious and non-noxious stimulations. On contrast, cells recorded at the levels of the VPm and VPl were not activated by noxious stimuli. These results emphasize the role of the posterior thalamic nuclei in pain processing.     

Trigeminothalamic fibre connections in the donkey (Equus asinus) studied by means of the retrograde cell degeneration method.

In this study the left thalamus of seven very young donkeys was transected and the trigeminothalamic fibre connections were investigated by means of the retrograde cell degeneration method. The animals were allowed to survive for a period of 15-45 days and the paraffin sections of the brain stem were stained according to the Klüver-Barrera and the thionine methods. It was found that the principal sensory trigeminal nucleus exhibited retrograde cell changes and cell losses, in its dorsal part, only at the side ipsilateral to the thalamic transection. As far as the nucleus of the spinal tract is concerned, slight changes were found, mainly contralaterally, in its oral subnucleus only. These findings suggest that in the donkey the main trigeminothalamic projection follows an ipsilateral course to the thalamus.     

Plastic synaptic reorganization in the sensorimotor cortex of adult cats after lesioning of the contralateral cerebellar nucleus interpositus

Intact cats and animals undergoing lesioning of the contralateral cerebellar nucleus interpositus between one and six months previously were used in this research, employing intracellular recording techniques and investigating the response of corticospinal neurons (CSN) to stimulating the aforementioned nucleus, the ipsilateral cerebellar nucleus interpositus, and the ventrolateral thalamic nucleus. A reduction was found in the stage of rise to peak in monosynaptic thalamocortical EPSP in CSN of operated animals, with a low axonal conduction velocity, pointing to distant terminal dendrosomatic sprouting and formation of new synapses at proximal sections of the CSN somatodendritic membrane. Findings are presented on formation of ipsilateral interpositothalamocortical projections duplicating similar contralateral projections in intact animals. Contralateral cortico-interposital collaterals were found in intact animals and similar sprouting of ipsilateral origin in those which had undergone surgery.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 22, No. 6, pp. 761–771, November–December, 1990.