Painful cutaneous laser stimuli induce event-related gamma-band activity in the lateral thalamus of humans.

Although the thalamus is an important module in "pain networks," there are few studies of the effect of experimental pain upon thalamic oscillations. We have now examined the hypothesis that, during a series of painful cutaneous laser stimuli, thalamic signals will show stimulus-related gamma-band spectral activity, which is modulated by attention to vs. distraction from the painful stimulus. When the series of laser stimuli was presented, attention was focused by counting the laser stimuli (count laser task), while distraction was produced by counting backward (count back plus laser task). We have studied the effect of a cutaneous laser on thalamic local field potentials and EEG activity during awake procedures (deep brain stimulation implants) for the treatment of essential tremor. At different delays after the stimulus, three low gamma- (30-50 Hz) and two high gamma-band (70-90 Hz) activations were observed during the two tasks. Greater high-gamma activation was found during the count laser task for the earlier window, while greater high-gamma activation was found during the count back plus laser task for the later window. Thalamic signals were coherent with EEG signals in the beta band, which indicated significant synchrony. Thalamic cross-frequency coupling analysis indicated that the phase of the lower frequency activity (theta to beta) modulated the amplitude of the higher frequency activity (low and high gamma) more strongly during the count laser task than during the count back plus laser task. This modulation might result in multiplexed signals each encoding a different aspect of pain.

Thalamic post-inhibitory bursting occurs in patients with organic dystonia more often than controls.

We now test the hypothesis that post-inhibitory bursting in the human pallidal receiving nucleus of the thalamus (ventral oral) mediates inhibitory pallido-thalamic transmission during dystonia. We have compared thalamic single neuron activity in nine patients with organic dystonia to that in a patient with psychogenic dystonia (Psyd) and in healthy waking monkeys. In organic dystonia, EMG power is commonly concentrated at the lowest frequency of the smoothed autopower spectrum (0.39Hz). Therefore, segments of spike trains with a signal-to-noise ratio ≥2 at 0.39Hz were termed dystonia frequency (DF) segments, which occurred more commonly during dystonia related to movement. Those with a SNR<2 were termed non-dystonia frequency (nDF) segments, which were associated with spontaneous dystonia. We concentrated on nDF activity since neuronal activity in our controls was measured at rest. Neuronal spike trains were categorized into those with post-inhibitory bursts (G, grouped), with single spikes (NG, non-grouped), or with both single spikes and bursts (I, intermediate). nDF spike trains in ventral oral had more G category firing in dystonia than in controls. The burst rate and the pre-burst silent period in nDF firing of organic dystonia were consistently greater than those of both the monkeys and the patient with Psyd. The distribution of the pre-burst silent period was bimodal with a longer mode of approximately GABAb (gamma amino butyric acid receptor-type b) duration. These results demonstrate distinct differences of post-inhibitory bursting in organic dystonia versus controls. The presence of inhibitory events consistent with GABAb duration suggests interventions for treatment of dystonia.

Thalamic physiology of intentional essential tremor is more like cerebellar tremor than postural essential tremor.

The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatment of tremor. Nine patients with essential tremor were divided clinically into two categories: one with a substantial component of tremor with intention (termed intention ET) and the other without (postural ET). These types of essential tremor were compared with patients having intention tremor plus other clinical signs of cerebellar disease (cerebellar tremor). Neurons in patients with either intention ET or cerebellar tremor had lower firing rates and lower spike×EMG coherence than those in patients with postural ET. Patients with intention ET had a lower spike×EMG phase lead than those with postural ET. Overall, thalamic activity measures of intention ET were different from postural ET but not apparently different from those of cerebellar tremor. One patient with the intention ET (number 4) had a good response to a left thalamotomy and then suffered a right cerebellar hemispheric infarct five years later. After the stroke the intention ET recurred, which is consistent with our hypothesis that intention ET is similar to that of the intention tremor which is characteristic of cerebellar lesions.

Mental arithmetic leads to multiple discrete changes from baseline in the firing patterns of human thalamic neurons.

Primate thalamic action potential bursts associated with low-threshold spikes (LTS) occur during waking sensory and motor activity. We now test the hypothesis that different firing and LTS burst characteristics occur during quiet wakefulness (spontaneous condition) versus mental arithmetic (counting condition). This hypothesis was tested by thalamic recordings during the surgical treatment of tremor. Across all neurons and epochs, preburst interspike intervals (ISIs) were bimodal at median values, consistent with the duration of type A and type B gamma-aminobutyric acid inhibitory postsynaptic potentials. Neuronal spike trains (117 neurons) were categorized by joint ISI distributions into those firing as LTS bursts (G, grouped), firing as single spikes (NG, nongrouped), or firing as single spikes with sporadic LTS bursting (I, intermediate). During the spontaneous condition (46 neurons) only I spike trains changed category. Overall, burst rates (BRs) were lower and firing rates (FRs) were higher during the counting versus the spontaneous condition. Spike trains in the G category sometimes changed to I and NG categories at the transition from the spontaneous to the counting condition, whereas those in the I category often changed to NG. Among spike trains that did not change category by condition, G spike trains had lower BRs during counting, whereas NG spike trains had higher FRs. BRs were significantly greater than zero for G and I categories during wakefulness (both conditions). The changes between the spontaneous and counting conditions are most pronounced for the I category, which may be a transitional firing pattern between the bursting (G) and relay modes of thalamic firing (NG).

Neural activities of tactile cross-modal working memory in humans: an event-related potential study.

In the present study, we examined the neural mechanisms underlying cross-modal working memory by analyzing scalp-recorded event-related potentials (ERPs) from normal human subjects performing tactile-tactile unimodal or tactile-auditory cross-modal delay tasks that consisted of stimulus-1 (S-1, tactile), interval (delay), and stimulus-2 (S-2, tactile or auditory). We hypothesized that there would be sequentially discrete task-correlated changes in ERPs representing neural processes of tactile working memory, and in addition, significant differences would be observed in ERPs between the unimodal task and the cross-modal task. In comparison to the ERP components in the unimodal task, two late positive ERP components (LPC-1 and LPC-2) evoked by the tactile S-1 in the delay of the cross-modal task were enhanced by expectation of the associated auditory S-2 presented at the end of the delay. Such enhancement might represent neural activities involved in cross-modal association between the tactile stimulus and the auditory stimulus. Later in the delay, a late negative component (LNC) was observed. The amplitude of LNC depended on information retained during the delay, and when the same information was retained, this amplitude was not influenced by modality or location of S-2 (auditory S-2 through headphones, or tactile S-2 on the left index finger). LNC might represent the neural activity involved in working memory. The above results suggest that the sequential ERP changes in the present study represent temporally distinguishable neural processes, such as the cross-modal association and cross-modal working memory.

Plasticity of pain-related neuronal activity in the human thalamus.

Strokes and other forms of injury to the central nervous system cause changes in function because of the injuries themselves and indirectly because injuries cause expression of neural plasticity. Studies in humans undergoing neurosurgical procedures for implantation of electrodes for deep brain stimulation and for making lesions in the brain have contributed understanding of both normal and abnormal functions of the somatic sensory system. This chapter will specifically discuss the reorganization of the ventral caudal (Vc) sensory nucleus of the thalamus that occurs in connection with pain conditions after strokes and spinal cord injuries. It is shown that pain is associated with expression of neural plasticity that alters maps of noxious and innocuous stimulation in the thalamus and affect processing of sensory information. Results from studies of neural activity in the thalamus in humans will be compared with results from animal studies.

Physiological changes in primate somatosensory thalamus induced by deafferentation are dependent on the spinal funiculi that are sectioned and time following injury.

The importance of spike bursts in thalamo-cortical processing of sensory information has received an increasing amount of interest over the past several years. Previously it has been reported that short high-frequency spike trains (3-8 action potentials occurring at 67-167 Hz), or spike bursts, are increased in both human and non-human primate thalamus following deafferentation. Here we examine the effects of lesion of the ventral spinal quadrant alone versus combined lesion of the ventral and dorsal spinal quadrants on the evoked and spontaneous spike trains in thalamic neurons. A total of 1175 neurons were sampled from 13 animals, three intact, six with ventral quadrant lesions (three with prolonged survival and three with short-term survival after spinal lesion) and four with combined ventral and dorsal quadrant lesions. Detailed analysis was conducted on 256 of these neurons, which revealed that thalamic neurons of animals with ventral quadrant lesions had elevated burst and non-burst spike rates while neurons from animals with combined ventral-dorsal lesions showed two types of change. Neurons in the forelimb areas showed increased bursts without a change in non-burst activity, while neurons in lateral VPL without receptive fields showed very low non-burst activity, but high burst spike rates. The magnitude of the effects produced by ventral-lateral spinal lesions was more pronounced in the short-term survival animals than in the long-term survival animals. These results show that the effects of deafferentation on the physiological properties of thalamic neurons are dependent on the afferent tract or tracts that are lesioned and the time after lesion.

Single-neuron analysis of human thalamus in patients with intention tremor and other clinical signs of cerebellar disease.

Tremor that occurs as a result of a cerebellar lesion, cerebellar tremor, is characteristically an intention tremor. Thalamic activity may be related to cerebellar tremor because transmission of some cerebellar efferent signals occurs via the thalamus and cortex to the periphery. We have now studied thalamic neuronal activity in a cerebellar relay nucleus (ventral intermediate-Vim) and a pallidal relay nucleus (ventralis oral posterior-Vop) during thalamotomy in patients with intention tremor and other clinical signs of cerebellar disease (tremor patients). The activity of single neurons and the simultaneous electromyographic (EMG) activity of the contralateral upper extremity in tremor patients performing a pointing task were analyzed by spectral cross-correlation analysis. EMG spectra during intention tremor often showed peaks of activity in the tremor-frequency range (1.9-5.8 Hz). There were significant differences in thalamic neuronal activity between tremor patients and controls. Neurons in Vim and Vop had significantly lower firing rates in tremor patients than in patients undergoing thalamic surgery for pain (pain controls). Other studies have shown that inputs to Vim from the cerebellum are transmitted through excitatory connections. Therefore the present results suggest that tremor in these tremor patients is associated with deafferentation of the thalamus from cerebellar efferent pathways. The thalamic X EMG cross-correlation functions were studied for cells located in Vim and Vop. Neuronal and EMG activity were as likely to be significantly correlated for cells in Vim as for those in Vop. Cells in Vim were more likely to have a phase lag relative to EMG than were cells in Vop. In monkeys, cells in the cerebellar relay nucleus of the thalamus, corresponding to Vim, are reported to lead movement during active oscillations at the wrist. In view of these monkey studies, the present results suggest that cells in Vim are deafferented and have a phase lag relative to tremor that is not found in normal active oscillations. The difference in phase of thalamic spike X EMG activity between Vim and Vop may contribute to tremor because lesions of pallidum or Vop are reported to relieve cerebellar tremor.

Microelectrode studies of normal organization and plasticity of human somatosensory thalamus.

Microelectrode studies of single units in the human thalamus during stereotactic surgery offer a unique opportunity to study the organization and plasticity of the sensory thalamus. In this review the authors present results using single-unit microelectrode recording in the mapping of human sensory thalamus in a variety of patients. First they outline the overall organization of the human sensory thalamus, including both somatosensory and pain pathways. They also show that the sensory maps for receptive and projection fields can be altered during pathologic states such as amputation and spinal transection. Additionally, the sensory maps show plasticity during states with abnormal patterns of motor activity, like dystonia. Lastly, they discuss the processing of painful and emotionally laden sensory experiences through the thalamus. The physiologic results of thalamic pain processing are discussed in relation to the sensory-limbic model of pain. The studies reviewed demonstrate the spectrum of stimulus processing and plasticity of both painful and nonpainful signals by the human thalamus.

Thalamic single neuron activity in patients with dystonia: dystonia-related activity and somatic sensory reorganization.

Indirect evidence suggests that the thalamus contributes to abnormal movements occurring in patients with dystonia (dystonia patients). The present study tested the hypothesis that thalamic activity contributes to the dystonic movements that occur in such patients. During these movements, spectral analysis of electromyographic (EMG) signals in flexor and extensor muscles of the wrist and elbow exhibited peak EMG power in the lowest frequency band [0-0.78 Hz (mean: 0.39 Hz) dystonia frequency] for 60-85% of epochs studied during a pointing task. Normal controls showed low-frequency peaks for <16% of epochs during pointing. Among dystonia patients, simultaneous contraction of antagonistic muscles (cocontraction) at dystonia frequency during pointing was observed for muscles acting about the wrist (63% of epochs) and elbow (39%), but cocontraction was not observed among normal controls during pointing. Thalamic neuronal signals were recorded during thalamotomy for treatment of dystonia and were compared with those of control patients without motor abnormality who were undergoing thalamic procedures for treatment of chronic pain. Presumed nuclear boundaries of a human thalamic cerebellar relay nucleus (ventral intermediate, Vim) and a pallidal relay nucleus (ventral oral posterior, Vop) were estimated by aligning the anterior border of the principal sensory nucleus (ventral caudal, Vc) with the region where the majority of cells have cutaneous receptive fields (RFs). The ratio of power at dystonia frequency to average spectral power was >2 (P < 0.001) for cells in presumed Vop often for dystonia patients (81%) but never for control patients. The percentage of such cells in presumed Vim of dystonia patients (32%) was not significantly different from that of controls (31%). Many cells in presumed Vop exhibited dystonia frequency activity that was correlated with and phase-advanced on EMG activity during dystonia, suggesting that this activity was related to dystonia. Thalamic somatic sensory activity also differed between dystonia patients and controls. The percentage of cells responding to passive joint movement or to manipulation of subcutaneous structures (deep sensory cells) in presumed Vim was significantly greater in patients with dystonia than in control patients undergoing surgery for treatment of pain or tremor. Dystonia patients had a significantly higher proportion of deep sensory cells responding to movement of more than one joint (26%, 13/52) than did "control" patients (8%, 4/49). Deep sensory cells in patients with dystonia were located in thalamic maps that demonstrated increased representations of parts of the body affected by dystonia. Thus dystonia patients showed increased receptive fields and an increased thalamic representation of dystonic body parts. The motor activity of an individual sensory cell was related to the sensory activity of that cell by identification of the muscle apparently involved in the cell's receptive field. Specifically, we defined the effector muscle as the muscle that, by contraction, produced the joint movement associated with a thalamic neuronal sensory discharge, when the examiner passively moved the joint. Spike X EMG correlation functions during dystonia indicated that thalamic cellular activity less often was related to EMG in effector muscles (52%) than in other muscles (86%). Thus there is a mismatch between the effector muscle for a thalamic cell and the muscles with EMG correlated with activity of that cell during dystonia. This mismatch may result from the reorganization of sensory maps and may contribute to the simultaneous activation of multiple muscles observed in dystonia. Microstimulation in presumed Vim in dystonia patients produced simultaneous contraction of multiple forearm muscles, similar to the simultaneous muscle contractions observed in dystonia. (ABSTRACT TRUNCATED)

Tremor-frequency (3-6 Hz) activity in the sensorimotor arm representation of the internal segment of the globus pallidus in patients with Parkinson's disease.

Neurons in the internal segment of the globus pallidus (GPi) oscillate at approximately the frequency of parkinsonian tremor. However, the correlation of that activity with tremor has not previously been studied. We now describe the relationship between single neuron activity in the arm sensorimotor portion of GPi and upper extremity tremor in patients with Parkinson's disease. There was a significant concentration of power in the tremor-frequency range (3-6 Hz) for 11/44 GPi neurons. However, pallidal tremor-frequency activity correlated significantly with electromyogram (EMG) activity during tremor for only a single GPi neuron. These data are most consistent with the hypothesis that the output of neurons in GPi is transformed in thalamus by a non-linear mechanism, before transmission via the cortex to the spinal motorneurons that drive movement.

Stereotactic thalamotomy in the treatment of essential tremor of the upper extremity: reassessment including a blinded measure of outcome.

The effectiveness of high frequency stimulation of the thalamic nucleus ventralis intermedius (Vim-HFS) for treatment of tremor has been studied by blinded assessment. The effectiveness of thalamotomy for essential tremor of the upper extremity by use of a blinded measure of outcome is now reported. Thalamotomy was performed in 21 patients (three operated on bilaterally) with medically intractable, essential tremor. Assessments of function, handwriting/drawing, and tremor amplitude were done before and at 3 and 12 months after surgery. The handwriting/drawing score was rated by a neurologist blinded to patient identity, laterality, and operative status. By comparison with baseline, both the total functional score and the total score from blinded assessment of handwriting/drawing improved significantly at 3 and 12 months after surgery. The two scores were significantly correlated, suggesting that the blinded assessment is a good predictor of a total disability from tremor. Complications after unilateral thalamotomy included transient dysarthria, permanent perioral numbness, and permanent mild disequilibrium in one patient each. Permanent mild dysarthria occurred in two of three patients operated bilaterally. Thus a blinded assessment of outcome establishes that unilateral thalamotomy is an effective, safe procedure for the treatment of essential tremor.

The role of the thalamus and basal ganglia in parkinsonian tremor.

The mechanism of parkinsonian tremor may involve a central oscillator, peripheral feedback to the central nervous system (CNS), or both. The thalamus or the globus pallidus is the most likely site for a central oscillator and would be predicted to generate thalamic tremor-related activity characterized, respectively, by calcium spike-associated bursts and by maximal tremor-related activity in the pallidal relay nucleus of thalamus. Thalamic spike trains demonstrate neither of these characteristics. However, cross-correlation, latency, and transfer function analysis indicate that sensory feedback is a critical element in the relationship between thalamic activity and parkinsonian tremor. Therefore, thalamic spike train activity is most consistent with parkinsonian tremor being mediated by peripheral inputs involved in either an unstable reflex loop or sensory modulation of a central oscillator.

Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury.

Stimulation of the somatosensory system is more likely to evoke pain in patients with chronic pain after nervous system injury than in patients without somatosensory abnormalities. We now describe results of stimulation through a microelectrode at microampere thresholds (threshold microstimulation; TMIS) in the region of the human thalamic principal sensory nucleus (ventral caudal; Vc) during operations for treatment of movement disorders or of chronic pain. Patients were trained preoperatively to use a standard questionnaire to describe the location (projected field) and quality of sensations evoked by TMIS intraoperatively. The region of Vc was divided on the basis of projected fields into areas representing the part of the body where the patients experienced chronic pain (pain affected) or did not experience chronic pain (pain unaffected) and into a control area located in the thalamus of patients with movement disorders and no experience of chronic pain. The region of the Vc was also divided into a core region and a posterior-inferior region. The core was defined as the region above a standard radiologic horizontal line (anterior commissure-posterior commissure line; ACPC line) where the majority of cells responded to innocuous somatosensory stimulation. The posterior-inferior area was a cellular area posterior and inferior to the core. In both the core and the posterior-inferior regions, the proportion of sites where TMIS evoked pain was larger in pain-affected and unaffected areas than in control areas. The number of sites where thermal (warm or cold) sensations were evoked was correspondingly smaller, so that the total of pain-plus-thermal (sensation of warmth or cold) sites was the same in all areas. Therefore, sites pain where stimulation evoked pain in patients with neuropathic pain (i.e., pain following an injury to the nervous system) may correspond to sites where thermal sensations were evoked by stimulation in patients without somatosensory abnormality.

Distribution of cardiovascular related cells within the human thalamus.

Representation of cardiovascular function has not been investigated in the human thalamus. In the rat, the insular cortex is the principal forebrain site of cardiovascular representation whose afferents originate from a circumscribed thalamic area (nucleus ventralis posterolateralis-parvicellular portion, VPLpc). We therefore evaluated 4481 thalamic cells for phasic cardiovascular activity using extracellular recording techniques in 60 unanesthetized patients undergoing neurosurgical procedures. We identified 26 cells with phasic activity strongly related to the cardiac cycle in 10 patients. These cells clustered within the ventrocaudal nucleus of the thalamus (the principal sensory nucleus analogous to the ventral posterior thalamic group in the rat and monkey) and were equally distributed between the right and left sides. The majority of these cells (17/26) showed peaks of phasic neuronal activity within 50 ms of the peak systolic pressure; 35% had peripheral cutaneous fields in areas to which cardiac pain is often referred. We suggest that these cells may be involved in the integration of afferent baroreceptor information; may possibly be concerned with the generation and/or processing of central cardiac pain in humans; and that their derangement may possibly contribute to the lethal cardiovascular disturbances which occur in fatal familial insomnia.

Thalamic neuronal activity correlated with essential tremor.

Animal studies suggest that an olivocerebello-bulbospinal pathway mediates harmaline induced tremor, which resembles essential tremor in humans. However, recent evidence suggests that thalamocortical pathways participate in essential tremor. Thalamic single neuron activity has been analysed during thalamotomy for essential tremor. It has been shown by spectral cross correlation analysis that thalamic activity has a significant, linear relation to forearm EMG activity during tremor. The presence of this tremor related activity at the site where a lesion abolishes essential tremor suggests that the thalamus has an important role in the mechanism of essential tremor.

Patterns of bursting occurring in thalamic cells during parkinsonian tremor.

It has been proposed that parkinsonian tremor is produced either by the activity of an intrinsic thalamic pacemaker or by the oscillation of an unstable long loop reflex arc. The former (central) hypothesis proposes that overactivity of neurons in the internal segment of the globus pallidus inhibits or hyperpolarizes thalamic neurons. When hyperpolarized, thalamic cells oscillate with bursting of the type associated with low threshold calcium spikes (low threshold spike-bursts). Low threshold spike-bursts can be identified by particular patterns of interspike intervals within the burst. The alternative (peripheral) hypothesis proposes that tremor results from oscillation of a reflex arc transmitting activity from muscle stretch receptors to thalamus, motor cortex, and back to the stretched muscle. When the gain of this reflex is increased, the arc may become unstable and oscillate. Oscillations produced by peripheral inputs may produce an acceleration-deceleration pattern within the burst which results in sinusoidal modulation of a spike train if bursting is periodic. We have assessed these two hypotheses by studying the pattern of interspike intervals occurring within bursts recorded in patients with parkinsonian tremor. The spike trains were analysed for 118 cells located in the ventral nuclear group including ventralis intermedius (thalamic cerebellar relay nucleus, n=48) and ventralis oralis posterior (thalamic pallidal relay nucleus, n=39) of patients with parkinsonian tremor. Two cells recorded in ventralis intermedius of a sleeping patient with chronic pain showed bursting activity similar to the low threshold spike-bursts recorded in sleeping animals, suggesting a common mechanism for low threshold spike-bursts across species. Forty-two cells recorded in patients with parkinsonian tremor (ventralis intermedius, n=19; ventralis oralis posterior, n=12) were classified as tremor-related cells because their activity was characterized by both a concentration of power at tremor frequency and significant correlation with tremor. Eleven tremor-related cells, 10 located in ventralis intermedius or ventralis oralis posterior and most responding to sensory inputs, had an acceleration-deceleration pattern of intraburst firing. Only one cell, a tremor-related cell in ventralis intermedius, showed the pattern expected of presumed low threshold spike-bursts. Therefore, intraburst interspike interval patterns consistent with either the central or the peripheral hypothesis were recorded in the thalamus of patients with parkinsonian tremor. Twenty-one tremor-related cells (15 cells in ventralis intermedius or ventralis oralis posterior) had bursts with intraburst interspike intervals which were independent of position of the interspike interval within the burst. Therefore, the activity of the majority of cells was not consistent with either hypothesis, suggesting that another oscillatory process may contribute to parkinsonian tremor.

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.