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Biomedical subjects

F A Lenz

Publications and source records attributed to F A Lenz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Facilitation of responses to AMPA but not kainate by cyclothiazide in primate somatosensory thalamus.

This study examines the possibility of multiple ionotropic non-N-methyl-D-aspartate (NMDA) receptors in the chief sensory nuclei of the primate thalamus. Cyclothiazide, an antagonist of rapid desensitization of non-NMDA receptors, is shown to produce a facilitation of responses to the synthetic agonist (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) but not kainate or NMDA in cells of the ventral posterior lateral and medial thalamic nuclei in the anesthetized monkey. These differential effects suggest the presence of multiple ionotropic non-NMDA excitatory amino acid receptors in the primate ventral posterior (VP) thalamus. Cyclothiazide-sensitive excitatory amino acid receptors have important roles in mechanisms of plasticity and excitotoxicity in other neural systems and so may mediate similar mechanisms in the somatosensory thalamus.

Animals↗
PubMed1998

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.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

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.

Action Potentials↗
PubMed1998

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.

Electromyography↗
PubMed1998

Neuronal activity in the region of the thalamic principal sensory nucleus (ventralis caudalis) in patients with pain following amputations.

Thalamic neuronal activity has not been studied in a primate model of peripheral nerve injury. We now report neuronal activity in the region of the human principal sensory nucleus of thalamus (ventralis caudalis) in awake patients during the physiologic exploration that precedes surgical procedures for treatment of stump pain and movement disorders. All patients with amputations showed increased thalamic representations of the stump as reflected in both receptive and projected field maps. This suggested that thalamic re-organization involved both the afferent inputs from and the perceptual representation of the limb. The spontaneous activity of neurons in the region of ventralis caudalis representing the limb with the stump (stump area) was significantly different from that in other areas of the region of ventralis caudalis in patients with amputations (stump control areas) and in patients with movement disorders (control areas). The mean interspike intervals were significantly shorter for cells located in stump areas than for those located in stump control or control areas. Cells in all areas were found to fire in three different patterns: B group (burst) characterized by bursting activity, R group (relay) characterized as a Poisson process, and III group characterized by non-bursting, non-Poisson activity. Cells in the B group were significantly more common in stump control (41%) and stump areas (33%) than in control areas (15%). Bursting cells were found to have patterns consistent with the occurrence of a calcium spike (spike-burst pattern). The spike-burst pattern was most common among cells with receptive fields in the stump area. In these cells firing between bursts (primary event rate) was significantly higher than other cells in the region of ventralis caudalis, suggesting that spike-bursts are not due to hyperpolarization, i.e. low-threshold spikes. Spike-bursts often occur as a result of low-threshold spikes, when the cell is hyperpolarized. In contrast, spike-bursts in these patients were associated with increased interburst firing rates in cells with receptive fields. Thus bursting of these cells may have been due to high-threshold dendritic calcium spikes evoked by afferent input. In that case bursting could be involved in activity-dependent changes in thalamic function following deafferentation through a calcium-mediated mechanism.

Amputation, Surgical↗
PubMed1998

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.

Adult↗
PubMed1998

Pallidal activity during dystonia: somatosensory reorganisation and changes with severity.

A woman with progressive, medically intractable right upper limb dystonia underwent a pallidotomy with only transient improvement. During the procedure her dystonia became more severe as she repeatedly made a fist to command in order to provoke dystonia transiently (movement provoked dystonia). Comparisons within cells in the internal segment of the globus pallidus (Gpi) disclosed that the firing rate was the same at rest, with making a fist, and during movement provoked dystonia. However, the firing rate compared between cells decreased significantly throughout the procedure as the patient made a fist repeatedly. During the second half of the procedure the firing rate of cells in the Gpi was similar to that in hemiballismus. The proportion of cells in the GPi which responded to sensory stimulation was significantly higher in dystonia (53%) than in hemiballismus (13%). These results suggest that pallidal activity can correlate inversely with the severity of dystonia, perhaps due to activity dependent changes in neuronal function resulting from repeated voluntary movement.

Antiparkinson Agents↗
PubMed1998

Neurons in the human thalamic somatosensory nucleus (Ventralis caudalis) respond to innocuous cool and mechanical stimuli.

A population of neurons in the principal somatosensory nucleus of human thalamus (ventralis caudalis, Vc) had a significant tonic, graded response to cool stimuli and also responded to innocuous mechanical stimuli (mechanical-cool neurons). These neurons were clustered at the dorsal aspect of medial Vc. Stimulation at the sites where these neurons were recorded evoked tingling sensations in the part of the body including or adjacent to the receptive field of these neurons. These neurons may contribute to the mechanism that mediates the perception of cold in man.

Action Potentials↗
PubMed1998

Painful stimuli evoke potentials recorded over the human anterior cingulate gyrus.

Clinical studies of cingulotomy patients and imaging studies predict that the human cingulate gyrus might display pain-related activity. We now report potentials evoked by painful cutaneous stimulation with a CO2 laser (LEP) and recorded from subdural electrodes over the medial wall of the hemisphere. In response to facial laser stimulation on both sides, a negative (latency 211-242 ms) and then a positive wave (325-352 ms) were recorded from the cortex of right medial wall and from the falcine dura overlying the left medial wall. Medial wall LEPs were similar to scalp LEPs and were largest over the anterior cingulate and superior frontal gyri just anterior to motor cortex contralateral to the side of stimulation. These results demonstrate that there is significant direct nociceptive input to the human anterior cingulate gyrus (Brodmann's area 24).

Adult↗
PubMed1998

Painful stimuli evoke potentials recorded from the parasylvian cortex in humans.

Cutaneous stimulation of the face and hand with a CO2 laser in three awake patients evoked potentials (LEPs) recorded from the dominant left parasylvian cortex. These were recorded by means of a subdural grid of electrodes implanted for evaluation of epilepsy. Stimulation of the contralateral face resulted in waveforms consisting of a negative potential (N2, 162 +/- 5 ms; mean +/- SE) followed by a positive potential (P2, 340 +/- 18 ms). Both waves occurred at longer latency after hand than after facial stimulation. N2 and P2 potentials recorded from the grid correspond well in morphology to those recorded from the scalp in four additional patients tested with the same stimulation paradigm. The N2 waves recorded from the subdural grid occurred at significantly shorter latencies than did those recorded from the scalp (184 +/- 6 ms), but the P2 waves at the grid occurred at significantly longer latencies than did those recorded at the scalp (281 +/- 13 ms). The amplitudes of the potentials recorded from the grid were maximal over the parietal operculum both for contralateral stimulation of the face or hand and for ipsilateral stimulation of the face. Potentials also were recorded in this area after stimulation of the ipsilateral hand. The cortical distributions of these potentials suggest that their generators are located in the parietal operculum or in the insula, or in both, consistent with previous PET, magnetoencephalographic, and scalp LEP source analyses. These previous analyses provide indirect evidence of nociceptive input to parasylvian cortex because the interpretation of each analysis incorporates multiple assumptions. The present results are the first direct evidence of nociceptive input to the human parasylvian cortex.

Adult↗
PubMed1998

Ablative therapy for movement disorders. Thalamotomy for Parkinson's disease.

Thalamotomy for Parkinson's disease is a well-established procedure that has been in use for more than 40 years. Technologic advances, such as computerized and magnetic resonance imaging, and refinement of stereotactic techniques have increased the safety and efficacy of this procedure. Current studies reveal good results in 70% to 90% of patients. Reported transient neurologic deficits occur in up to 60% of patients undergoing this procedure, although the highest permanent complication rates have decreased to around 10% to 20%. These data suggest the safety and efficacy of thalamotomy as a primary therapeutic option for selected patients with parkinsonian tremor.

Humans↗
PubMed1997

Pallidotomy for hemiballismus: efficacy and characteristics of neuronal activity.

A patient with unremitting, medically intractable hemiballismus underwent a pallidotomy that abolished his involuntary movements. Firing rates of cells in the internal segment of the globus pallidus (GPi) recorded during this procedure were significantly lower than those observed during pallidotomy for Parkinson's disease, either "on" or "off" medication. Firing patterns in hemiballismus were characterized by low-frequency modulation of the firing rate. These results are consistent with the hyperkinetic model, which suggests that hemiballismus results from decreased inhibition of the pallidal relay nucleus of the thalamus by the GPi. The efficacy of surgery in the case of hemiballismus demonstrates that pallidotomy can be an effective treatment for this condition and suggests that patterned neuronal activity in the GPi is important in the mechanism of hyperkinetic disorders.

Action Potentials↗
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↗
PubMed1997

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior.

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.

Brain Mapping↗
PubMed1996

Characterization of cortical spreading depression by imaging of intrinsic optical signals.

The spatiotemporal progression of cortical spreading depression was investigated by imaging of activity-dependent intrinsic optical signals in rat sensorimotor cortex. In contrast to the traditional conception of a uniformly propagating event, the evolution of the spreading depression was characterized by an asymmetrical propagating wavefront and a non-uniform dispersion of optical signals behind the wavefront. As these optical signals are a reflection of underlying molecular and metabolic processes, the imaging approach to spreading depression might constitute a useful technique for investigating the functional organization as well the pathophysiology of the cerebral cortex.

Animals↗