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PubMed2004

Posture-related oscillations in human cerebellar thalamus in essential tremor are enabled by voluntary motor circuits.

The mechanism of essential tremor (ET) is unclear. Animal models of tremor and functional imaging studies in ET predict that the cerebellum and a cerebellar recipient thalamic nucleus (ventral intermediate, Vim) should exhibit oscillatory activity during rest and during tremor due to abnormal olivo-cerebellar activity. Physiologic responses of 152 single neurons were recorded during awake mapping of the ventral thalamus in seven patients with ET prior to thalamotomy. During postural tremor, spectral cross-correlation analysis demonstrated that 51% of the neurons studied exhibited a concentration of power at tremor frequency that was correlated with electromyography, i.e., tremor neurons. During rest, thalamic neurons did not exhibit tremor-frequency activity. Among the three thalamic nuclei surveyed, Vim had a significantly higher proportion of tremor neurons than did the principal somatic sensory nucleus (ventral caudal, Vc) or a pallidal recipient thalamic nucleus (ventral oral posterior, Vop). Neurons related to active movement (voluntary neurons) had significantly greater tremor-related activity than did nonvoluntary neurons. These findings are not consistent with a model of continuous olivo-cerebellar driving of the motor cortex through thalamic connections. Instead ET may be facilitated by motor circuits that enable tremor-related thalamic activity during voluntary movement. Additionally, a subgroup of tremor neurons with proprioceptive inputs were identified that may allow sensory feedback to access the central tremor network.

Action Potentials↗
PubMed2006

Neural representations of temporally modulated signals in the auditory thalamus of awake primates.

In sensory systems, the thalamus has historically been considered a relay station. Neural representations of temporal modulations in the auditory system undergo considerable changes as they pass from the inferior colliculus (IC) to the auditory cortex. We sought to determine in awake primates the extent to which auditory thalamic neurons contribute to these transformations. We tested the temporal processing capabilities of medial geniculate body (MGB) neurons in awake marmoset monkeys using repetitive click stimuli. MGB neurons were able to synchronize to periodic clicks at repetition rates significantly higher than auditory cortex neurons. Unlike responses in the MGB of anesthetized animals, >40% of MGB neurons in awake marmosets displayed nonsynchronized discharges when stimulated by high click rates (short interclick intervals). Such nonsynchronized MGB responses typically occurred at higher repetition rates than those observed in auditory cortex. In contrast to auditory cortex neurons, many MGB neurons exhibited both synchronized and nonsynchronized discharge patterns. In both MGB and auditory cortex, synchronized and nonsynchronized responses represented complementary ranges of interclick intervals (1/click rate). Furthermore, the temporal processing abilities of some MGB neurons were sensitive to the spectrotemporal parameters of the click stimuli used. Together, these findings suggest that MGB neurons participate in active transformations of the neural representations of temporal modulations from IC to auditory cortex. In particular, the MGB appears to be the first station in the auditory ascending pathway in which substantial nonsynchronized responses emerge.

Acoustic Stimulation↗
PubMed2004

Auditory thalamus bursts in anesthetized and non-anesthetized states: contribution to functional properties.

Over the last 10 years, high-frequency bursts of action potentials have been the subject of intense researches to understand their potential role in information encoding. Based on recordings from auditory thalamus neurons (n = 302) collected during anesthesia (pentobarbital, urethan, or ketamine/xylazine), waking (W), and slow-wave sleep (SWS), we investigated how bursts participate to frequency tuning, intensity-function, response latency (and latency variability), and stimulus detectability. Although present in all experimental conditions, bursts never dominated the cells mode of discharge: the highest proportion was found during ketamine/xylazine anesthesia (22%), the lowest during waking (4.5%). In all experimental conditions, bursts preferentially occurred at or around the cells best frequency (BF), thus increasing the frequency selectivity. This effect was observed at both the intensities producing the highest and the lowest evoked responses. Testing the intensity-functions indicated that for most of the cells, there was no systematic relationship between burst proportion and responses strength. Under several conditions (W, SWS, and urethan), when cells exhibited bursts >20%, the variability of their response latency was reduced in burst mode compared with single-spike mode. During W, this effect was accompanied by a reduction of the response latency. Finally, a receiver operating characteristic analysis indicated no particular relation between bursts and stimulus detectability. Compared with single-spike mode, which is present for broader frequency ranges, the prominence of bursts at the BF should contribute to filter information reaching the targets of medial geniculate cells at both cortical and subcortical levels.

Acoustic Stimulation↗
PubMed2005

Activity properties and location of neurons in the motor thalamus that project to the cortical motor areas in monkeys.

The activity of neurons in the motor nuclei of the thalamus that project to the cortical motor areas (the primary motor cortex, the ventral and dorsal premotor cortex, and the supplementary motor area) was investigated in monkeys that were performing a task in which wrist extension and flexion movements were instructed by visuospatial cues before the onset of movement. Movement was triggered by a visual, auditory, or somatosensory stimulus. Thalamocortical neurons were identified by a spike collision, and exhibited 2 distinct types of task-related activity: 1) a sustained change in activity during the instructed preparation period in response to the instruction cues (set-related activity); and 2) phasic changes in activity during the reaction and movement time periods (movement-related activity). A number of set- and moment-related neurons exhibited direction selectivity. Most movement-related neurons were similarly active, irrespective of the different sensory modalities of the cue for movement. These properties of neuronal activity were similar, regardless of their target cortical motor areas. There were no significant differences in the antidromic latencies of neurons that projected to the primary and nonprimary motor areas. These results suggest that the thalamocortical neurons play an important role in the preparation for, and initiation and execution of, the movements, but are less important than neurons of the nonprimary cortical motor areas in modality-selective sensorimotor transformation. It is likely that such transformations take place within the nonprimary cortical motor areas, but not through thalamocortical information channels.

Action Potentials↗
PubMed2006

Distinctive glycinergic currents with fast and slow kinetics in thalamus.

We examined functional properties of inhibitory postsynaptic currents (IPSCs) evoked by medial lemniscal stimulation, spontaneous IPSCs (sIPSCs), and single-channel, extrasynaptic currents evoked by glycine receptor agonists or gamma-aminobutyric acid (GABA) in rat ventrobasal thalamus. We identified synaptic currents by reversal at E(Cl) and sensitivity to elimination by strychnine, GABA(A) antagonists, or combined application. Glycinergic IPSCs featured short (about 12 ms) and long (about 80 ms) decay time constants. These fast and slow IPSCs occurred separately with monoexponential decays, or together with biexponential decay kinetics. Glycinergic sIPSCs decayed monoexponentially with time constants, matching fast and slow IPSCs. These findings were consistent with synaptic responses generated by two populations of glycine receptors, localized under different nerve terminals. Glycine, taurine, or beta-alanine applied to excised membrane patches evoked short- and long-duration current bursts. Extrasynaptic burst durations resembled fast and slow IPSC time constants. The single, intermediate time constant (about 22 ms) of GABA(A)ergic IPSCs cotransmitted with glycinergic IPSCs approximated the burst duration of extrasynaptic GABA(A) channels. We noted differences between synaptic and extrasynaptic receptors. Endogenously activated glycine and GABA(A) receptor channels had higher Cl- permeability than that of their extrasynaptic counterparts. The beta-amino acids activated long-duration bursts at extrasynaptic glycine receptors, consistent with a role in detection of ambient taurine or beta-alanine. Heterogeneous kinetics and permeabilities implicate molecular and functional diversity in thalamic glycine receptors. Fast, intermediate, and slow inhibitory postsynaptic potential decays, mostly attributed to cotransmission by glycinergic and GABAergic pathways, allow for discriminative modulation and integration with voltage-dependent currents in ventrobasal neurons.

Action Potentials↗
PubMed1984

Visuomotor functions of central thalamus in monkey. I. Unit activity related to spontaneous eye movements.

The region in and around the thalamic internal medullary lamina (IML) in the cat recently has been shown to contain neurons active with ocular saccades and responding to visual stimuli. In the present study, single-unit microelectrode recordings were made in the corresponding thalamic region of the alert monkey in order to determine whether neurons with similar properties existed. Our objective was to specify the functional characteristics of these thalamic cells in the monkey, since 1) cell populations in the central thalamus form an important link between brain stem structures, such as superior colliculus and paramedian pontine reticular formation, and cortical areas, such as frontal eye field and inferior parietal lobule; and 2) most neurophysiological information on these structures with regard to gaze mechanisms has been obtained in primates. In this first part of the study we report observations on 164 thalamic units whose activity was related to the performance of spontaneous eye movements, head fixed. The animals had been trained on a visual discrimination task but photic stimuli were used only for calibrating the eye-position recording and for inducing small saccades and smooth pursuit. The experiments were performed in dim red light and in total darkness. Three types of units were found: 67 saccadic burst units, 58 saccade pause-rebound units, and 39 eye-position units. Sixty-two of the burst units had a directional preference. Most of the on-directions were contraversive, and it was in such units that the lead time of firing before saccades was the longest (up to at least 400 ms). Some of the burst units had a movement field, others fired more intensively and with a longer lead time, depending on the eccentricity of the eye position reached in orbit. The five units with no directional preference were the ones showing the best relation of burst duration with saccade duration. Three types of pause-rebound units were distinguished, depending on whether the saccadic pause or the postsaccadic burst was the most conspicuous event or the pause occurred after saccade offset. The three types were called, respectively, omnipausers, omnirebound cells, and late pausers. Omnipausers and omnirebound cells had no directional preference but their typical firing patterns occurred very consistently with all saccades, even less than 2 degrees. In a few units, the rebound progressively faded away in total darkness. The relation of firing rate of eye-position units with eccentricity of the eyes in orbit was analyzed. Fluctuations in time and a hysteresis effect were found to affect this relation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Correlation of effects of general anesthetics on somatosensory neurons in the primate thalamus and cortical EEG power.

The effects of two types of general anesthetic on the neurophysiological properties of the primate somatosensory thalamus were correlated with effects on frontal cortex electroencephalographic (EEG) power and spectral properties. Graded doses of the intravenous agent methohexital sodium (METH) were studied in 12 cells in three monkeys on a halothane baseline anesthetic. Low doses of METH (0.2-1.0 mg/kg) produced a reduction of EEG power but had no effects on spontaneous or evoked thalamic activity. EEG power showed maximal attenuation after 2.0 mg/kg METH, whereas decreases in thalamic activity were first noted over a similar moderate dose range (2.0-5.0 mg/kg). The physiological parameter most sensitive to METH was the spontaneous activity, which showed initial changes in rate and moderate doses followed by marked inhibition at higher doses. Finally, the high dose of METH (10.0 mg/kg) produced marked reduction in all neurophysiological parameters with recovery over the following 30-45 min. The effects of the volatile anesthetic halothane were studied on 15 cells in four monkeys anesthetized with pentobarbital sodium. The low dose of halothane (0.25%) produced a facilitation of responses to cutaneous stimuli as well as decrease in the rate and burst patterns in the spontaneous activity. The power in the EEG was not affected at this concentration. The responses of the cells to the mechanical stimuli at moderate doses (0.5-1.0%) of halothane returned to the baseline magnitude, whereas spontaneous activity remained unaffected compared with initial effects. EEG power was reduced by 1% halothane. Finally, all neurophysiological parameters showed profound reduction at the highest halothane concentrations (2.0-3.0%) with recovery over the next 30-45 min. In conclusion, the two classes of anesthetics most commonly used for acute neurophysiological studies in the primate show well-defined thresholds at which changes in the response properties of thalamic neurons are produced. This threshold for the barbiturates and halothane can be predicted by monitoring of cortical EEG.

Adjuvants, Anesthesia↗
PubMed2000

Temporary inactivation in the primate motor thalamus during visually triggered and internally generated limb movements.

To better understand the contribution of cerebellar- and basal ganglia-receiving areas of the thalamus [ventral posterolateral nucleus, pars oralis (VPLo), area X, ventral lateral nucleus, pars oralis (VLo), or ventral anterior nucleus, pars parvicellularis (VApc)] to movements based on external versus internal cues, we temporarily inactivated these individual nuclei in two monkeys trained to make visually triggered (VT) and internally generated (IG) limb movements. Infusions of lignocaine centered within VPLo caused hemiplegia during which movements of the contralateral arm rarely were performed in either task for a short period of time ( approximately 5-30 min). When VT responses were produced, they had prolonged reaction times and movement times and a higher incidence of trajectory abnormalities compared with responses produced during the preinfusion baseline period. In contrast, those IG responses that were produced remained relatively normal. Infusions centered within area X never caused hemiplegia. The only deficits observed were an increase in reaction time and movement amplitude variability and a higher incidence of trajectory abnormalities during VT trials. Every other aspect of both the VT and IG movements remained unchanged. Infusions centered within VLo reduced the number of movements attempted during each block of trials. This did not appear to be due to hemiplegia, however, as voluntary movements easily could be elicited outside of the trained tasks. The other main deficit resulting from inactivation of VLo was an increased reaction time in the VT task. Finally, infusions centered within VApc caused IG movements to become slower and smaller in amplitude, whereas VT movements remained unchanged. Control infusions with saline did not cause any consistent deficits. This pattern of results implies that VPLo and VLo play a role in the production of movements in general regardless of the context under which they are performed. They also suggest that VPLo contributes more specifically to the execution of movements that are visually triggered and guided, whereas area X contributes specifically to the initiation of such movements. In contrast, VApc appears to play a role in the execution of movements based on internal cues. These results are consistent with the hypothesis that specific subcircuits within the cerebello- and basal ganglio-thalamo-cortical systems preferentially contribute to movements based on external versus internal cues.

Analysis of Variance↗
PubMed2000

Cornea-responsive medullary dorsal horn neurons: modulation by local opioids and projections to thalamus and brain stem.

Previously, it was determined that microinjection of morphine into the caudal portion of subnucleus caudalis mimicked the facilitatory effects of intravenous morphine on cornea-responsive neurons recorded at the subnucleus interpolaris/caudalis (Vi/Vc) transition region. The aim of the present study was to determine the opioid receptor subtype(s) that mediate modulation of corneal units and to determine whether opioid drugs affected unique classes of units. Pulses of CO(2) gas applied to the cornea were used to excite neurons at the Vi/Vc ("rostral" neurons) and the caudalis/upper cervical spinal cord transition region (Vc/C1, "caudal" neurons) in barbiturate-anesthetized male rats. Microinjection of morphine sulfate (2.9-4.8 nmol) or the selective mu receptor agonist D-Ala, N-Me-Phe, Gly-ol-enkephalin (DAMGO; 1.8-15.0 pmol) into the caudal transition region enhanced the response in 7 of 27 (26%) rostral units to CO(2) pulses and depressed that of 10 units (37%). Microinjection of a selective delta ([D-Pen(2,5)] (DPDPE); 24-30 pmol) or kappa receptor agonist (U50488; 1.8-30.0 pmol) into the caudal transition region did not affect the CO(2)-evoked responses of rostral units. Caudal units were inhibited by local DAMGO or DPDPE but were not affected by U50,488H. The effects of DAMGO and DPDPE were reversed by naloxone (0.2 mg/kg iv). Intravenous morphine altered the CO(2)-evoked activity in a direction opposite to that of local DAMGO in 3 of 15 units, in the same direction as local DAMGO but with greater magnitude in 4 units, and in the same direction with equal magnitude as local DAMGO in 8 units. CO(2)-responsive rostral and caudal units projected to either the thalamic posterior nucleus/zona incerta region (PO/ZI) or the superior salivatory/facial nucleus region (SSN/VII). However, rostral units not responsive to CO(2) pulses projected only to SSN/VII and caudal units not responsive to CO(2) projected only to PO/ZI. It was concluded that the circuitry for opioid analgesia in corneal pain involves multiple sites of action: inhibition of neurons at the caudal transition region, by intersubnuclear connections to modulate rostral units, and by supraspinal sites. Local administration of opioid agonists modulated all classes of corneal units. Corneal stimulus modality was predictive of efferent projection status for rostral and caudal units to sensory thalamus and reflex areas of the brain stem.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Cellular mechanisms underlying activity patterns in the monkey thalamus during visual behavior.

We show for the first time with in vitro recording that burst firing in thalamic relay cells of the monkey is evoked by activation of voltage-dependent, low threshold Ca(2+) spikes (LTSs), as has been described in other mammals. Due to variations in LTS amplitude, the number of action potentials evoked by an LTS could vary between 1 and 8. These data confirm the presence of two modes of firing in the monkey for thalamic relay cells, tonic and burst, the latter related to the activation of LTSs. With these details of the cellular processes underlying burst firing, we could account for many of the firing patterns we recorded from the lateral geniculate nucleus of the thalamus in behaving monkeys. In particular, we found clear evidence of burst firing during alert wakefulness, which had been thought to occur only during sleep or certain pathological states. This makes it likely that the burst firing seen in awake humans has the same cellular basis of LTSs, and this supports previous suggestions that burst firing represents an important relay mode for visual processing.

Action Potentials↗
PubMed2001

Effect of attentive fixation in macaque thalamus and cortex.

Attentional modulation of neuronal responsiveness is common in many areas of visual cortex. We examined whether attentional modulation in the visual thalamus was quantitatively similar to that in cortex. Identical procedures and apparatus were used to compare attentional modulation of single neurons in seven different areas of the visual system: the lateral geniculate, three visual subdivisions of the pulvinar [inferior, lateral, dorsomedial part of lateral pulvinar (Pdm)], and three areas of extrastriate cortex representing early, intermediate, and late stages of cortical processing (V2, V4/PM, area 7a). A simple fixation task controlled transitions among three attentive states. The animal waited for a fixation point to appear (ready state), fixated the point until it dimmed (fixation state), and then waited idly to begin the next trial (idle state). Attentional modulation was estimated by flashing an identical, irrelevant stimulus in a neuron's receptive field during each of the three states; the three responses defined a "response vector" whose deviation from the line of equal response in all three states (the main diagonal) indicated the character and magnitude of attentional modulation. Attentional modulation was present in all visual areas except the lateral geniculate, indicating that modulation was of central origin. Prevalence of modulation was modest (26%) in pulvinar, and increased from 21% in V2 to 43% in 7a. Modulation had a push-pull character (as many cells facilitated as suppressed) with respect to the fixation state in all areas except Pdm where all cells were suppressed during fixation. The absolute magnitude of attentional modulation, measured by the angle between response vector and main diagonal expressed as a percent of the maximum possible angle, differed among brain areas. Magnitude of modulation was modest in the pulvinar (19-26%), and increased from 22% in V2 to 41% in 7a. However, average trial-to-trial variability of response, measured by the coefficient of variation, also increased across brain areas so that its difference among areas accounted for more than 90% of the difference in modulation magnitude among areas. We also measured attentional modulation by the ratio of cell discharge due to attention divided by discharge variability. The resulting signal-to-noise ratio of attention was small and constant, 1.3 +/- 10%, across all areas of pulvinar and cortex. We conclude that the pulvinar, but not the lateral geniculate, is as strongly affected by attentional state as any area of visual cortex we studied and that attentional modulation amplitude is closely tied to intrinsic variability of response.

Analysis of Variance↗
PubMed2001

Oligodendroglial ganglioglioma with anaplastic features arising from the thalamus.

Anaplastic gangliogliomas with an oligodendroglial component are exceedingly rare tumors of uncertain growth potential. We report a 17-year-old female with a massive ganglioglioma containing anaplastic oligodendroglioma apparently arising from the thalamus. Two weeks after partial resection, she was started on a regimen including escalated doses of topotecan in combination with a fixed-dosage intensification regimen of cisplatin, cyclophosphamide and vincristine with subsequent hyperfractionated external beam radiotherapy. She currently has stable disease.

Adolescent↗
PubMed2005

Representation of somatosensory modalities in pathways ascending from the spinal anterolateral funiculus to the thalamus demonstrated by lesions in man.

Patients with cordotomies (16), and brainstem (17) or thalamic (30) infarcts, all except cordotomies verified by magnetic resonance imaging (MRI), have been subjected to quantitative sensory perception threshold testing (QST) for touch (von Frey), mechanical pain, sharpness, innocuous warmth and cold, and heat pain in the maximally affected body area and its unaffected contralateral mirror image region. Some patients were tested twice at widely spaced time intervals; no qualitative differences were found. Results show that all modalities are dissociable from one another by lesions at all levels tested, so that there must be separable representation for each of the six modalities tested. In the lower (crossed symptoms and signs), but not the upper (uncrossed symptoms), deficits for all modalities (except for touch) were more marked than at higher levels. At the level of the thalamus, deficits for innocuous and noxious thermal modalities but not for mechanical pain were recorded in the case of lesions of the principal somatosensory relay nucleus (VPL/Vc), while more medial thalamic lesions resulted in deficits for mechanical pain but not for heat pain or innocuous thermal modalities; there is a marked deficit for sharpness caused by lesions at both thalamic sites.

Afferent Pathways↗
PubMed1995

Sleeping cells in the human thalamus.

Neurons in the lateral thalamus of a patient undergoing stereotactic surgery were found to fire in a characteristic bursting pattern only when the patient was asleep. These novel observations are consistent with animal studies in which the tonic firing pattern of thalamic neurons during wakefulness changes to a bursting pattern during slow-wave sleep.

Adult↗
PubMed1992

Neurophysiological atlas created by mapping of clinical responses elicited on electrical stimulation of the human thalamus.

By computer processing of intraoperative neurophysiological data and intraoperative X-ray films, and using a 0.5-mm-step three-dimensional atlas created by interpolation of Schaltenbrand-Bailey's atlas, a neurophysiological atlas based on clinical responses upon electrical stimulation of the subcortical structures of patients who underwent stereotactic surgery in the awake state was created. There was considerable overlap in the distribution of motor and sensory responses in the vicinity of the ventral intermediate (VIM) thalamus: however, motor responses, particularly irregular movements, tended to be confined within the VIM and ventro-oralis posterior (VOP), whereas sensory responses tended to be localized in the VIM and ventroposterolateral nuclei, with considerable extension into the ventroposterior subthalamic region. In either motor or sensory responses, no definite somatotopic pattern could be determined.

Brain Mapping↗
PubMed1993

Microinjection of lidocaine into human thalamus: a useful tool in stereotactic surgery.

A new method was developed to aid in the localization of the optimal site for a permanent lesion in movement disorder patients undergoing stereotactic thalamotomy. The method involved making small injections of a local anesthetic into the thalamus, which was also useful in assessing any possible side effects that could potentially arise from the lesion. Initial results indicate that 0.5 to 2-microliters injections of 2% lidocaine at appropriate sites in the thalamic ventrocaudal or ventrointermedius nucleus can produce a temporary marked suppression of tremor. In most cases the lidocaine induced effects mimicked those produced by high frequency electrical stimulation delivered to the same site. However, lidocaine had no effect at some sites where stimulation arrested tremor. This technique promises to be useful not only in the treatment of motor disorder patients but also in other cases where functional localization prior to lesioning is desirable.

Electric Stimulation↗
PubMed1993

CT and pathological study on radiofrequency-induced lesion in cat thalamus.

In order to observe the postoperative focal changes caused by radiofrequency lesions in the ventrolateral nucleus of the thalamus in stereotactic treatment of Parkinson's disease, similar lesions were produced in cat. The CT features and their correlative pathologic changes at different intervals were divided into three types, four stages and three zones. The degree of susceptibility of nervous tissue to radiofrequency, repair characteristics and the mechanism of CT enhancement are discussed in light of the pathologic changes.

Animals↗
PubMed1980

Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man.

Stimulation of the thalamus and internal capsule with Medtronic deep brain stimulation electrodes produced improvement in pain, hemiparesis, dystonia, torticollis, tremor. speech impairment and epilepsy. Stimulation at voltages above or below clinically effective levels (e.g., 6 V, 0.3 ms, 74 Hz) resulted in a loss of clinical efficacy. Somatosensory evoked responses (short and long latency) and depth electrode recordings were helpful in localisation and 'biocalibration' of electrical stimulation.

Adult↗