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Jonathan O Dostrovsky

Publications and source records attributed to Jonathan O Dostrovsky.

At least 19 recordsLinked to original sources
PubMed2006

Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease.

Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.

Aged↗
PubMed2006

Bursting activity of neurons in the human anterior thalamic nucleus.

Single unit microelectrode recordings were obtained under local anesthesia in 5 patients who underwent placement of deep brain stimulation electrodes in the anterior thalamic nucleus for control of intractable epilepsy. Of the 261 neurons recorded, 145 were in the anterior nucleus (AN), with the remainder ventral to AN in nucleus cucularis and dorsal dorsomedian nucleus (DM). 126 of the 261 neurons fired in bursts, and of these, 74 cells were analyzed in greater detail to characterize their bursting pattern. The bursts in 70% of the bursting neurons were characterized as low-threshold calcium spike (LTS) mediated bursts, on the basis of their intraburst firing pattern. The bursts of the remainder, although similar to LTS bursts, did not fulfil all of the criteria for an LTS burst and were termed atypical bursting cells. LTS and atypical bursting cells were found both within AN and in the nucleus cucularis and dorsal DM. The LTS bursting observed in these patients may be due to the altered electrophysiological state of the patients studied since LTS bursting in thalamus is usually only observed during sleep. This study describes for the first time the properties of this nucleus in humans and may be important in furthering our knowledge of thalamic mechanisms of epileptogenesis.

Action Potentials↗
PubMed2006

Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis.

We have previously demonstrated that application of the inflammatory irritant mustard oil (MO) to the rat molar tooth pulp induces central sensitization in nociceptive neurons within the contralateral ventroposterior medial (VPM) nucleus and posterior nuclear group (PO) of the thalamus as well as brainstem subnucleus caudalis (Vc) and subnucleus oralis (Vo). Since Vc and Vo are important relays of pulp afferent input to thalamus, the aim of this study was to test if local application of the synaptic blocker CoCl2 to Vc or Vo influences the pulp-induced thalamic central sensitization. The activity of 32 nociceptive-specific (NS) neurons within the rat VPM and immediately adjacent PO was recorded. Spontaneous activity, mechanoreceptive field (RF), mechanical activation threshold and evoked responses to graded mechanical stimuli were assessed before and after MO application to the pulp. MO application evoked immediate but short-lasting neuronal discharges in 21 of the 32 NS neurons tested, as well as central sensitization reflected in significant and long-lasting (> 60 min) RF expansion, decrease in activation threshold, and increase in graded pinch-evoked responses in all 32 NS neurons. CoCl2 applied to the ipsilateral Vc significantly attenuated these pulp-induced changes for 20 min or more. In contrast, CoCl2 applied to the ipsilateral Vo did not reverse this MO-induced central sensitization. Isotonic saline applied to Vc or Vo was also ineffective. These findings indicate that central sensitization induced in nociceptive neurons within VPM and PO by noxious stimulation of the tooth pulp is dependent upon the functional integrity of Vc but not Vo.

Animals↗
PubMed2006

Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect.

We conducted a retrospective analysis of long-term results of deep brain stimulation (DBS) for the treatment of neuropathic pain. Twenty-one patients had electrodes implanted in the ventrocaudalis thalamic nucleus (Vc) (n=13) or in both Vc and periaqueductal/periventricular gray matter (PAG/PVG) (n=8). After insertion of the electrodes, 9 patients (43%) had a substantial reduction in pain scores in the absence of stimulation (insertional effect). The effects of stimulation were studied right after surgery or upon return of the patients' pain after electrode insertion (stimulation trials). Patients with a greater than 50% reduction in pain scores were implanted with a pulse generator (IPG). Of interest, patients who had an insertional effect had a trend towards a successful stimulation trial (p=0.08). Overall, 13 of the 21 patients operated (62%) had a successful stimulation trial and received an IPG (12 with electrodes in Vc and one in both Vc and PAG/PVG). Seven patients (33%) did not benefit from stimulation and had the electrodes removed. One patient experienced a prolonged insertional effect and has not required stimulation. Of the 13 patients that received an IPG, 8 discontinued stimulation during the first year of treatment. Only 5 patients maintained long-term benefit (4 with stimulation in Vc and one in both Vc and PAG/PVG). The relatively low efficacy of DBS for the treatment of neuropathic pain stresses the need for further investigation and the exploration of new surgical targets.

Adult↗
PubMed2006

Dissociation of thalamic high frequency oscillations and slow component of sensory evoked potentials following damage to ascending pathways.

OBJECTIVE: Somatosensory evoked potentials (SEPs) recorded from the thalamus have a slow component and high frequency (approximately 1000 Hz) oscillations (HFOs). In this study, we examined how lesions in the sensory afferent pathway affect these components. METHODS: Thalamic SEPs to contralateral median nerve stimulation were recorded from deep brain stimulation electrodes in two patients. Patient 1 had spinal cord injury at the C4/5 level. Patient 2 had multiple sclerosis with mid brain lesions. Seven patients with no brain or cervical spinal cord lesions served as controls. RESULTS: In both patients, the low frequency component of the SEP (LF SEP) was delayed and/or prolonged and greatly decreased in amplitude compared with controls. HFOs were recorded in both patients. The latencies of onset and peak of the HFOs were approximately the same as those of the LF SEPs and their amplitudes were similarly reduced. However, their frequency was similar to that of the control group. Cortical SEPs were absent in both patients. CONCLUSIONS: Normal frequencies of thalamic HFOs in association with increased peak latencies, and decreased amplitudes provide further evidence that the HFOs are likely due to intrinsic oscillations in the thalamus rather than high frequency synchronous inputs. SIGNIFICANCE: Thalamic HFOs are closely associated with the LF SEP but are generated by a different mechanism.

Adult↗
PubMed2006

The motor thalamus in neurosurgery.

The motor thalamus is an important target for the treatment of tremor. It receives afferents from the cerebellum, globus pallidus internus, and substantia nigra and projects mainly to the motor cortex, premotor cortex, and supplementary motor area. Various nomenclatures have been proposed to subdivide the motor thalamus, none of which are universally accepted. Both thalamic lesions and high-frequency stimulation ameliorate tremor in diverse pathological conditions. Modern neurophysiological techniques have allowed the recording of the activity of thalamic neurons in patients with different clinical conditions. This has provided a better understanding of the functions of the motor thalamus in humans. The aim of the present article is to briefly review the major anatomic and physiological aspects of the motor thalamus as well as the electrophysiological findings described in humans undergoing surgical procedures.

Electrophysiology↗
PubMed2005

Human anterior cingulate cortex neurons encode cognitive and emotional demands.

The cortical mechanisms and substrates of cognitive and emotional demands are poorly understood. Lesion studies and functional imaging implicate the anterior cingulate cortex (ACC). The caudal ACC (cACC) has been implicated in cognitive processes such as attention, salience, interference, and response competition, mostly on the basis of neuroimaging results. To test the hypothesis that individual cACC neurons subserve these functions, we monitored neuronal activity from single cells in the cACC while subjects were engaged in a mental arithmetic task, the cognitively demanding counting Stroop task, and/or the emotional Stroop interference task. We now report the first direct measures of single neurons in humans identifying a population of cACC neurons that respond differentially or in a graded manner to cognitively demanding high- and low-conflict Stroop tasks, including those with emotional valence. These data indicate that cACC neurons may be acting as salience detectors when faced with conflict and difficult or emotional stimuli, consistent with neuroimaging results of cACC responses to abrupt sensory, novel, task-relevant, or painful stimuli.

Brain Mapping↗
PubMed2005

Firing rates of pallidal neurons are similar in Huntington's and Parkinson's disease patients.

According to the now classical basal ganglia-thalamocortical circuitry model, the chorea of Huntington's disease (HD) and the hypokinesia in Parkinson's disease (PD) are explained by a decrease in the inhibitory output (reduced firing rates) from the globus pallidus internus (GPi) in HD and increased output in PD. Differences between firing patterns might also be a factor contributing to the different symptoms, however. To test the predictions of the model we examined neuronal firing rates and patterns in two HD patients and 14 PD patients. Single-cell, microelectrode recordings were obtained from awake patients undergoing stereotactic surgery for implantation of deep brain stimulating (DBS) electrodes in the GPi. The mean neuronal firing rate in the GPi of HD patients was 81.8+/-4.3 Hz (mean+/-SEM), which was not significantly different from that in PD patients (89.9+/-3.0 Hz). Firing pattern analyses using measurements of burst index, coefficient of variation, and percentage participation of spikes in bursts revealed, however, that GPi neurons in HD patients fired in a more regular pattern (fewer "bursts") than in PD patients. These results suggest that the rate-based model does not adequately explain the motor abnormalities present in the two HD patients studied. Furthermore, the findings did reveal a difference between firing patterns in the HD and PD groups, thereby supporting the role of altered firing patterns in the pathophysiology of these diseases.

Action Potentials↗
PubMed2005

Evaluation of the time course of plasma extravasation in the skin by digital image analysis.

UNLABELLED: Plasma extravasation (PE) can be triggered by neurotransmitters as part of a neuroinflammatory response. We present a technique based on video digital image processing that provides a simple, noninvasive, reliable, and quantitative method for measuring the time course and extent of PE in the skin. After intravenous infusion of Evans Blue dye, stimulation of the saphenous nerve caused the skin on the dorsomedial region of the hind paw to become dark blue. The change in reflectance of the skin was recorded with a monochrome video camera. Images were digitized and analyzed with inexpensive or public domain software. The change in pixel intensity was determined in a selected region. Stimulation at 4 Hz caused greater darkening of the skin than at 1 Hz, and this was confirmed with spectrophotometric measurements of Evans Blue content. The NK1 receptor antagonist CP-99, 994 blocked saphenous nerve and substance P-induced darkening of the skin. The results indicate that our measurement gives results similar to those obtained with classic methods that are widely accepted as an indication of PE. This simple and quick method reveals the extent, time course, and location of PE, is cheap to implement and easy to learn, and thus represents a useful and alternative tool for studies of PE and its modulation. PERSPECTIVE: This article presents a simple technique with which to evaluate the time course and extent of plasma extravasation in the skin of animal models of neuroinflammation. The technique is well suited to answer questions about basic physiologic mechanisms of neuroinflammation and should also be useful in drug testing studies.

Animals↗
PubMed2004

Eye movement-related responses of neurons in human subthalamic nucleus.

Intraoperative microelectrode single unit recordings are routinely made in the subthalamic nucleus (STN) of awake and alert Parkinson's disease (PD) patients during surgery for implantation of deep brain stimulation (DBS) electrodes. These recordings not only assist in determining the optimal target for electrode implantation, but also offer the unique opportunity to study movement-evoked responses from the basal ganglia. We report on the responses of human STN neurons to eye movements from eight PD patients (five men and three women). Twenty percent (18/89) of tested STN neurons showed responses to eye movements. Patients made pro-saccades, voluntary saccades or smooth pursuit eye movements in four directions: up, down, left, right. The majority of STN neurons (72% or 13/18), that responded to eye movements were found in the ventral half of the nucleus, while 58% (22/38) of STN neurons that had somatic responses were found in the dorsal half of the nucleus. The firing rate for STN oculomotor neurons was 33+/-15 Hz (n = 18), which was not different from that reported previously for STN neurons. Most neurons only responded to eye movements in a single direction, but 17% (3/18) showed responses to more than one direction. The majority of responses (17/18) to eye movements were increases in firing rate although one neuron did show a pause in firing with eye movement onset. The phasic changes in firing rate in response to eye movement usually occurred up to 250 ms following eye movement onset. Neurons were found that showed task-specific responses to cued versus self-paced saccades, responded to both passive limb movement and voluntary eye movement, and appeared to show either visual or attentional responses. These human physiological data, in conjunction with previous anatomical studies, suggest that the STN might have an oculomotor role. Although there is no evidence that STN is responsible for driving eye movements, it may have a role in either sensory feedback, corollary discharge, or in focusing the substantia nigra pars reticulata to allow a saccade to occur through disinhibition of the superior colliculus.

Action Potentials↗
PubMed2004

Very fast oscillations evoked by median nerve stimulation in the human thalamus and subthalamic nucleus.

Very fast oscillations (VFOs; 500-1,500 Hz) are associated with sensory-evoked potentials (SEPs), but their origin is unknown. To characterize the origins of VFOs, we studied 35 patients with deep brain stimulation (DBS) electrodes [15 with thalamic and 20 with the subthalamic nucleus (STN) electrodes]. We recorded median nerve stimulation-evoked SEPs from the thalamus and STN with microelectrodes during stereotactic surgery and from the contacts of the DBS electrodes postoperatively. We also examined the firing of individual neurons in thalamus in relation to the VFOs. In the thalamus, VFOs with frequencies around 1,000 Hz were superimposed on slow potentials. Both slow and fast SEP components showed phase reversals in the somatosensory thalamus [ventralis caudalis (Vc)]. Median nerve poststimulus time histograms showed that single thalamic neurons fired at preferred times at intervals between 0.8 to 1.2 ms that were synchronous with the VFOs, although the neurons fired only once or a few times per trial. In the STN, low-amplitude SEPs with VFOs were observed at a latency similar to the thalamic SEPs. The VFOs from STN probably represent volume conduction, possibly from the medial lemniscus. We conclude that the thalamic VFOs are generated within Vc and that they induce time-locked firing in a network of neurons.

Adult↗
PubMed2004

Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus.

The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinson's disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 microm away. Stimulation at high frequencies (100-300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15-20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.

Action Potentials↗
PubMed2004

Subthalamic nucleus deep brain stimulation for parkinson's disease after successful pallidotomy: clinical and electrophysiological observations.

Unilateral pallidotomy is an effective treatment for contralateral parkinsonism and dyskinesia, yet symptoms progress in many patients. Little is known about whether such patients obtain a useful response to subsequent bilateral subthalamic nucleus deep brain stimulation (STN DBS). Changes in Unified Parkinson's Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores, medication requirements, and dyskinesias were measured. Clinical outcomes were compared to patients with de novo STN DBS. Neuronal recordings were performed. STN DBS resulted in a significant reduction in UPDRS Motor scores (42.1%; 95% confidence interval [CI], 26.9-57.4; P = 0.03), comparable with de novo STN DBS surgery (41%; 95% CI, 26-46%; P < 0.001). There was also less change in dyskinesia duration and disability scores (P = 0.017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy.

Activities of Daily Living↗
PubMed2004

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.

Adult↗
PubMed2004

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

OBJECTIVE: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN). METHODS: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS. RESULTS: A large SEP with a mean latency of 17.9+/-1.7 ms was recorded from thalamic contacts. Phase reversal occurred at the horizontal level of the anterior commissure-posterior commissure line. Smaller potentials with similar latency but no reversal could be recorded from STN electrodes. CONCLUSIONS: We propose that the thalamic SEP is generated by excitatory post-synaptic potentials in sensory relay neurons in nucleus ventrocaudalis. A small potential in STN at a similar latency, may be due to volume conduction from thalamus. Intraoperative and postoperative SEP recordings from DBS electrodes could be used to determine the optimal position of the contacts relative to the sensory pathways and the choice of contacts for chronic stimulation.

Adult↗
PubMed2004

Cingulotomy for psychiatric disease: microelectrode guidance, a callosal reference system for documenting lesion location, and clinical results.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)- and microelectrode recording-guided cingulotomy for patients with psychiatric disorders and to develop a new method of mapping lesion location in anterior cingulate cortex that takes into account the significant interindividual variability in callosal morphometry. METHODS: MRI and microelectrode recording were used to guide placement of radiofrequency lesions in patients with obsessive-compulsive disorder (n = 21) or affective disorders (n = 5). Postoperative improvement was evaluated with the Yale-Brown Obsessive-Compulsive Scale in 15 of the 21 obsessive-compulsive disorder patients studied. From the postoperative MRI scans, we developed a coordinate system for position in the anterior cingulate cortex. The callosal line passes from the most anterior point of the corpus callosum (c = 0) to the most posterior (c = 100). We reconstructed the lesions onto a sagittal map from the Talairach and Tournoux atlas using the distance along the callosal line and the distance above the upper surface of the corpus callosum. RESULTS: The location of neuronal activity distinguished gray and white matter and was useful in delineating the upper and lower cortical banks of the cingulate gyrus, the cingulate bundle, and the corpus callosum. This information was used to place the lesions. Lesions typically were 6 to 8 mm in diameter on T2-weighted MRI scans. The inferior margins were along the corpus callosum from c = 16 to c = 38. Four of 15 patients with obsessive-compulsive disorder had a documented decrease of more than 35% on the Yale-Brown Obsessive-Compulsive Scale, but only one patient had a sustained benefit for more than 1 year. CONCLUSION: Microelectrode recording is useful for lesion placement. Our system for reporting location in anterior cingulate cortex normalizes for differences in callosal morphometry. These techniques may aid future study.

Adult↗
PubMed2004

Histological analysis of the location of effective thalamic stimulation for tremor. Case report.

Chronic electrical stimulation of the thalamus is an effective treatment for essential and parkinsonian tremor. Although the preferred surgical target is generally accepted to lie within the ventral intermediate nucleus (Vim), the relationship between the surgically defined target and the true histologically defined target is addressed in only a few reports, due in large measure to the need for advanced cytoarchitectonic techniques to define the borders of the thalamic nuclei. The authors report on a patient who underwent effective thalamic deep brain stimulation (DBS) for tremor. By defining the boundaries of the thalamic nuclei, they were able to relate effective DBS to electrode location within the anterior region of the ventral posterior lateral nucleus--the proprioceptive shell of the sensory nucleus--and the posteroventral region of the ventral lateral nucleus, which are equivalent to the Vim defined by Hassler, et al.

Brain Mapping↗