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P M Dougherty

Publications and source records attributed to P M Dougherty.

At least 37 records · Page 2Linked to original sources
PubMed1999

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.

Brain Mapping↗
PubMed1999

Responses of primate spinomesencephalic tract cells to intradermal capsaicin.

The responses of 32 spinomesencephalic tract cells to intradermal capsaicin were examined in anesthetized monkeys. Wide dynamic range (n = 20) and nociceptive specific (n = 6) cells showed two types of excitatory responses to intradermal injection of capsaicin. The first excitatory response shown by the majority of wide dynamic range (n = 13) and nociceptive specific (n = 4) cells was consistent with their sensitization by capsaicin. The cells showed an acute and prolonged increase in ongoing activity with capsaicin injection. Responses to mechanical stimuli were substantially increased after capsaicin and an expansion of receptive field was often observed. The responses of the same cells to excitatory amino acid agonists applied locally by iontophoresis also increased. All cells showing sensitization were antidromically activated from periaqueductal gray regions dorsal to the sulcus limitans. Electrical stimulation at these sites did not affect the ongoing or evoked discharges of these cells. The second excitatory response of wide dynamic range (n = 5) and nociceptive specific (n = 1) cells was a novel pattern not consistent with sensitization. These cells nevertheless showed an acute and prolonged increase in background activity after capsaicin injection. Yet, there was no change or a decrease in responses to cutaneous stimuli, no evidence for change in receptive field size and no increase in responses to locally released excitatory amino acids. These cells projected to regions in the periaqueductal gray ventral to the sulcus limitans. Electrical stimulation at these sites produced a decrease in spontaneous activity of the same cell. Low threshold mesencephalic-projecting neurons (n = 6) showed a single inhibitory pattern (n = 4) of responses to capsaicin. The injection produced an acute decrease in spontaneous activity that was sustained for at least 30 min after injection. The responses to cutaneous stimuli and to excitatory amino acids were also substantially reduced. Low threshold cells were found that projected to both dorsal-lateral and ventral-lateral regions of the periaqueductal gray. In summary, three patterns of responses shown by primate spinomesencephalic tract cells to intradermal capsaicin appear dependent on the functional regions of the periaqueductal gray to which they project. These results suggest that inputs of spinomesencephalic tract neurons to the periaqueductal gray may evoke important components of the systemic response to the neurogenic hyperalgesia produced by intradermal capsaicin.

Animals↗
PubMed1999

Monkey insular cortex neurons respond to baroreceptive and somatosensory convergent inputs.

To investigate possible convergence of autonomic and somatosensory input in the insula of the non-human primate, extracellular single-unit recordings were obtained from 81 neurons (43 insular and 38 in surrounding cortex) during application of cutaneous nociceptive stimuli (pinch) and baroreceptor challenge in six anesthetized monkeys (Macaca fascicularis). All cells were also tested with light touch (brush) stimulation. Twenty-six units responded to blood pressure changes; 20 (80%) were identified within the insula (P < 0.001). The majority of these insular units (16/20) also responded to nociceptive pinch (convergent units). More units responsive to changes in blood pressure (unimodal and convergent) were found in the right (18/29, 62%) than in the left insular cortex (2/14, 14%)(P = 0.004). Twenty-nine insular neurons responded to nociceptive stimuli; 16 of these were convergent units and 13 showed unimodal responses to somatosensory stimuli alone. These cells had wide bilateral receptive fields including face, hand, foot and tail. Ten insular neurons were unresponsive to both sets of stimuli (non-responsive cells); significantly more of these cells (28/38) were identified in extrainsular locations (P < 0.01). We suggest that the primate insular cortex may be involved in the integration of cardiovascular function with somatosensory (principally nociceptive) input. This view supports the emerging role of the insular cortex as an important forebrain site of viscerosomatosensory regulation with clinical implications for cardiovascular regulation under conditions of stress and arousal.

Animals↗
PubMed1999

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.

Aged↗
PubMed1998

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.

Brain Mapping↗
PubMed1998

Characterization of baroreceptor-related neurons in the monkey insular cortex.

Insular neurons responsive to baroreceptor challenge have been identified in the rat, but not previously in primates. Characterization of baroreceptor-related neurons was performed in 15 anesthetized monkeys (Macaca fascicularis) using extracellular single-unit recording techniques. 131 units were investigated within the insula and surrounding regions. Based on their responses to phenylephrine hydrochloride (PE) and sodium nitroprusside (SNP), three types of units were distinguished: 35/131 (27%) sympathoexcitatory (SE), 12/131 (9%) sympathoinhibitory (SI) and 84 (64%) null units. More baroreceptive units were found within the insula (38/73, 52%) than in surrounding areas (9/58, 16%) (p < 0.001). Lateralization was indicated with more baroreceptive units being encountered within the right insula (28/44, 64%) than the left (10/29, 34%) (p = 0.02). The majority of the responsive units were located within the dysgranular and granular insula in layers II, III and V/VI. These data suggest that cardiovascular representation may occur in the primate insula as has been shown in other species.

Animals↗
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↗
PubMed1997

Time course of degenerative and regenerative changes in the dorsal horn in a rat model of peripheral neuropathy.

The time course of histochemical changes in the dorsal horn of rats subjected to an experimental peripheral neuropathy has been examined. Qualitative and quantitative analyses of the changes in dorsal horn staining were made for soybean agglutinin (SBA)-binding glycoconjugates, the soluble lectins RL-14.5 and RL-29, the growth-associated protein (GAP)-43, and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). These analyses were made at various time points after chronic constriction of the sciatic nerve. Quantitative analysis indicated that staining density increased in the normal territories stained for SBA-binding glycoconjugates, RL-14.5, RL-29, and GAP-43 on the neuropathic side compared with the control side. In addition, there was an extension of the territories stained for SBA-binding glycoconjugates and RL-29 ipsilateral to the injury. The peak increases occurred at 14 or 28 days, followed by a decrease toward control levels by 70 days. In contrast, the staining density for SP in the ipsilateral dorsal horn decreased at 3 and 5 days and reached a peak decrease at 14 days. Then, the staining for SP returned toward control values. The staining for CGRP was unchanged at all time points examined. Dorsal rhizotomies ipsilateral to the nerve injury in neuropathic rats indicated that the increases in staining were attributable to changes in primary afferent neurons. These data suggest that peripheral neuropathy causes complex degenerative and regenerative changes in the central branches of primary afferent neurons. The associated synaptic reorganization may contribute to the sensory abnormalities that accompany peripheral neuropathy.

Animals↗
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↗