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Biomedical subjects

A M Lozano

Publications and source records attributed to A M Lozano.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of acute stimulation through contacts placed on the motor cortex for chronic stimulation.

OBJECTIVES: We tried to determine which neural elements were activated in awake subjects by stimulation through contacts placed chronically on the motor cortex. METHODS: We recorded the motor effects of stimulation through 4 disc contacts placed in the subdural space over the motor cortex in 9 patients undergoing chronic stimulation for the control of pain or for the control of the rigidity of multiple system atrophy. RESULTS: Single stimuli could elicit short latency motor evoked potentials or facilitate active motoneurons in the contralateral limbs. The responsible neural elements had a short chronaxie (the pulse duration necessary to reach threshold with a stimulus intensity twice that required to reach threshold at the longest pulse duration used) and refractory period implying that they were myelinated axons. The facilitation was larger with cathodal than with anodal monopolar stimulation. The short latency facilitation in response to the second of two stimuli was greater at condition test intervals of 2-5 ms. This enhancement could be demonstrated with conditioning stimuli subthreshold for the excitation of active motoneurons suggesting that it arose, in part, at the level of the cortex. Single cortical stimuli could result in inhibition of voluntarily activated motoneurons. The inhibition was larger with cathodal than anodal monopolar stimulation. The responsible neural elements also had a short chronaxie and refractory period. CONCLUSIONS: Stimulation in awake subjects through contacts placed chronically over the motor cortex appears to activate axons in the cortex, which excite both corticospinal neurons and inhibitory neurons.

Adult↗
PubMed2001

Effects of internal globus pallidus stimulation on motor cortex excitability.

BACKGROUND: Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD. METHODS: The physiologic effects of internal globus pallidus (GPi) stimulation in seven patients with PD and seven age-matched healthy volunteers were studied. The stimulators were set at the optimal parameters (ON), at half the optimal amplitude (Half-Amp), or switched off (OFF) in random order. Patients were taking their usual medications. Magnetic stimulation was applied to the motor cortex, and motor evoked potentials (MEP) were recorded from the contralateral first dorsal interosseous muscle. Several excitatory and inhibitory pathways that have been found to be abnormal in PD were tested. RESULTS: The motor threshold (MT), MEP recruitment curve (stimulus intensities from 100 to 150% of MT), short and long interval intracortical inhibition, and intracortical facilitation were similar in the three stimulator conditions tested both at rest and during voluntary contraction. The silent period (SP) was longer in the OFF and Half-Amp conditions than in normal control subjects. In the stimulator ON condition, the SP was significantly reduced compared with the OFF condition and became similar to that in normal control subjects. CONCLUSIONS: GPi stimulation while on dopaminergic medications reduced the SP following magnetic stimulation but did not change corticospinal excitability or other measures of intracortical inhibition and facilitation. The reduction of SP may be related to the antidyskinetic and levodopa-blocking effects of ventral GPi stimulation.

Aged↗
PubMed2001

Functional correlates of pallidal stimulation for Parkinson's disease.

We measured regional cerebral blood flow with H2 15O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right-handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication-free state. Internal globus pallidus deep brain stimulation improved off-state United Parkinson's Disease Rating Scale motor ratings (37%, p < 0.002) and reduced timing errors (movement onset time, 55%, p < 0.01) as well as spatial errors (10%, p < 0.02). Concurrent regional cerebral blood flow recordings revealed a significant enhancement of motor activation responses in the left sensorimotor cortex (Brodmann area [BA] 4), bilaterally in the supplementary motor area (BA 6), and in the right anterior cingulate cortex (BA 24/32). Significant correlations were evident between the improvement in motor performance and the regional cerebral blood flow changes mediated by stimulation. With internal globus pallidus deep brain stimulation, improved movement initiation correlated with regional cerebral blood flow increases in the left sensorimotor cortex and ventrolateral thalamus and in the contralateral cerebellum. By contrast, improved spatial accuracy correlated with regional cerebral blood flow increases in both cerebellar hemispheres and in the left sensorimotor cortex. These results suggest that internal globus pallidus deep brain stimulation may selectively improve different aspects of motor performance. Multiple, overlapping neural pathways may be modulated by this intervention.

Adult↗
PubMed2001

Potentials recorded at the scalp by stimulation near the human subthalamic nucleus.

OBJECTIVE: To record the potentials evoked at the scalp by stimulation through electrodes targeted at the human subthalamic nucleus (STN) and to determine whether the responsible pathways continue to be excited or become blocked with high frequency stimulation. METHODS: We recorded the potentials evoked at the scalp in response to single and multiple stimuli delivered through STN contacts in 6 patients with Parkinson's disease. RESULTS: On 9/11 sides tested, single stimuli elicited a negative potential with latency of approximately 3 ms which was largest over the frontal region. Its short chronaxie (50 micros) and refractory period imply that it arose from the activation of low threshold neural elements, possibly myelinated axons. This potential could follow at 100 Hz. This early potential was sometimes followed by later negative potentials at approximately 5 ms (6/11 sides) and approximately 8 ms (8/11 sides). The responsible neural elements had the same short chronaxie. These potentials were augmented by paired stimuli at separations of 2-7 ms and by trains of stimuli at 200 Hz. CONCLUSIONS: Trains of stimuli delivered to the STN may excite low threshold neural elements which can transmit impulses at frequencies >100 Hz without blocking and which may produce postsynaptic facilitation at the cortex.

Electric Stimulation Therapy↗
PubMed2001

Lidocaine and muscimol microinjections in subthalamic nucleus reverse Parkinsonian symptoms.

Inactivation of neurones in the subthalamic nucleus (STN) of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated monkey model of Parkinson's disease has been shown to relieve parkinsonian motor symptoms. In patients with Parkinson's disease, neurones in the STN display hyperactive firing rates and rhythmic discharge activity such as tremor-related oscillations (3-8 Hz) and synchronous high-frequency oscillations (15-30 Hz). In this study, microinjections of lidocaine (n = 4) and muscimol, a GABA(A) receptor agonist (n = 2), were performed in the STN of six patients with Parkinson's disease to determine whether the focal suppression of STN neuronal activity can lead to an improvement in tremor, bradykinesia and rigidity. We also report the first use of microelectrode recording of the effects of microinjections on neuronal activity in the human brain (n = 2). Microinjections of 10-23 microl of lidocaine produced striking improvements in bradykinesia, limb tremor and rigidity in three out of three patients. These improvements were correlated with good therapeutic effects of subsequent STN deep brain stimulation performed in the same microelectrode trajectories as these injections. The most dramatic observation following lidocaine injections was the appearance of dyskinetic limb movements. In one patient, simultaneous microelectrode recording during an injection of 3.5 microl of lidocaine demonstrated a suppression of neuronal activity at distances of < 0.9 mm from the injection site, but no suppression was observed at > or = 1.2 mm from the injection site. Microinjections of 5-10 microl of muscimol in a region with tremor-related activity resulted in suppression of limb tremor in two out of two patients. Interestingly, in one of these patients, 4 Hz oscillatory activity was diminished in a neurone recorded 1.3 mm from the injection site, but there was no reduction in the mean firing rate or 20 Hz oscillatory activity. These results demonstrate that inactivation of neuronal activity in the STN of patients with Parkinson's disease improves motor symptoms. These findings also suggest that a focal block of the STN might alter the oscillatory activity of neurones located beyond the inhibited region.

Aged↗
PubMed2001

Networks mediating the clinical effects of pallidal brain stimulation for Parkinson's disease: a PET study of resting-state glucose metabolism.

Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic changes occur in Parkinson's disease patients treated with deep brain stimulation (DBS) of the GPi. We studied seven Parkinson's disease patients with FDG-PET to measure resting regional cerebral glucose utilization on and off GPi stimulation. We used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. We also quantified stimulation-related changes in the expression of a specific abnormal Parkinson's disease-related pattern of metabolic covariation (PDRP) that had been identified in earlier FDG-PET studies. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings (36%, P < 0.001) and significantly increased regional glucose metabolism in the premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi DBS also resulted in a significant (P < 0.01) decline in PDRP activity ipsilateral to stimulation, which correlated significantly with clinical improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS is associated with reduced expression of an abnormal Parkinson's disease-related metabolic network involving elements of the cortico-striato-pallido-thalamocortical and the cerebello-cortical motor loops.

Adult↗
PubMed2001

Deep brain stimulator electrodes used for lesioning: proof of principle.

OBJECTIVE: Patients with chronically implanted deep brain stimulator (DBS) electrodes can encounter complications requiring hardware removal. We assessed the safety and efficacy of using implanted DBS electrodes to create a therapeutic lesion before their removal. METHODS: Revision or removal of the DBS electrodes was required in two patients who had previously undergone DBS implantation. We conducted a series of in vitro experiments to confirm that the DBS electrodes could be used to generate radiofrequency lesions and to assess the relationship between radiofrequency parameters and lesion size. With this information, and with the approval of the hospital ethical review board, implanted electrodes were used to create incremental radiofrequency lesions in the thalamus in one patient and in the subthalamic nucleus in another. The procedures were performed under local anesthesia with contiguous contacts of the DBS lead connected to the active and reference sites of the RF generator to create a bipolar lesion. RESULTS: A 51-year-old man with essential tremor and a thalamic DBS required repeated battery changes secondary to tolerance and high voltage demands. Rather than replacing the battery, a radiofrequency thalamotomy was performed by using the existing left DBS electrode. At the 6-month follow-up examination, successful lesioning provided near complete tremor control. A second patient, a 50-year-old man with Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation, developed skin erosion over the DBS hardware. A subthalamic nucleus lesion was made through the right DBS electrode. Lesion position and size were confirmed with magnetic resonance imaging. CONCLUSION: Lesions can be made through chronically implanted DBS electrodes in a safe, graded fashion and can produce therapeutic benefit.

Device Removal↗
PubMed2001

Effects of apomorphine on subthalamic nucleus and globus pallidus internus neurons in patients with Parkinson's disease.

This study examines the effect of apomorphine (APO), a nonselective D(1)- and D(2)-dopamine receptor agonist, on the firing activity of neurons in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) in patients with Parkinson's disease (PD). Single-unit microelectrode recordings were conducted in 13 patients undergoing implantation of deep brain stimulation electrodes in STN and 6 patients undergoing a pallidotomy. Doses of APO (2.5-8 mg) were sufficient to produce an ON state, but not intended to induce dyskinetic movements. Following baseline recordings from a single neuron, APO was administered and the activity of the neuron followed for an average of 15 min. The spontaneous discharge of neurons encountered before (n = 309), during (n = 146, 10-60 min), and after the effect of APO had waned (n = 127, >60 min) was also sampled, and the response to passive joint movements was noted. In both nuclei, APO increased the overall proportion of spikes in burst discharges (as detected with Poisson "surprise" analysis), and a greater proportion of cells with an irregular discharge pattern was observed. APO significantly decreased the overall firing rates of GPi neurons (P < 0.01), but there was no change in the overall firing rate of neurons in the STN (P = 0.68). However, the mean firing rates of STN neurons during APO-induced movements (choreic or dystonic dyskinesias) that occurred in four patients were significantly lower than OFF-period baseline values (P < 0.05). Concurrent with a reduction in limb tremor, the percentage of cells with tremor-related activity (TCs) was found to be significantly reduced from 19 to 6% in the STN and 14 to 0% in the GPi following APO administration. APO also decreased the firing rate of STN TCs (P < 0.05). During the OFF state, more than 15% of neurons tested (STN = 93, GPi = 63) responded to passive movement of two or more joints. After APO, this proportion decreased significantly to 7% of STN cells and 4% of GPi cells (STN = 28, GPi = 26). These findings suggest that the APO-induced amelioration of parkinsonian symptoms is not solely due to a decrease in overall activity in the GPi or STN as predicted by the current model of basal ganglia function in PD.

Action Potentials↗
PubMed2001

Pallidotomy for parkinson disease: a review of contemporary literature.

OBJECT: The authors conducted an evidence-based review of contemporary published articles on pallidotomy to obtain an appraisal of this procedure in the treatment of Parkinson disease (PD). METHODS: A search of the Pubmed database performed using the key word "pallidotomy" yielded 263 articles cited between January 1, 1992, and July 1, 1999. Articles that included original, nonduplicated descriptions of patients with PD treated with radiofrequency pallidotomy were selected. In 85 articles identified for critical review, 1959 patients with PD underwent pallidotomies at 40 centers in 12 countries. There were 1735 unilateral (88.6%) and 224 bilateral procedures (11.4%). The mean age of the patients was 61.4+/-3.6 years and the mean duration of PD symptoms in these patients was 12.3+/-1.9 years. Microelectrode recordings were used in 46.2% of cases. Outcomes were objectively documented using the Unified Parkinson Disease Rating Scale (UPDRS) in 501 (25.6%) of the cases at 6 months and in 218 (11.1%) of the cases at 1 year. There was a consensus on the benefits of pallidotomy for off period motor function and on period, drug-induced dyskinesias, with variations in the extent of symptomatic benefit across studies. At the 1-year assessment, the mean improvement in the UPDRS motor score during off periods was 45.3% and the mean improvement in contralateral dyskinesias during on periods was 86.4%. The overall mortality rate was 0.4% and the rate of persistent adverse effects was estimated at 14%. Major adverse events, including intracerebral hemorrhages, contralateral weakness, and visual field defects, occurred in 5.3% of patients reported. CONCLUSIONS: Unilateral pallidotomy is effective and relatively safe in the treatment of PD; however, limited data are available on the long-term outcome of this procedure.

Globus Pallidus↗
PubMed2000

High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor.

It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization of neuronal firing in the basal ganglia. This study examines the discharge activity of 121 pairs of subthalamic nucleus (STN) neurons in nine PD patients undergoing functional stereotactic mapping. Four patients had a previous pallidotomy. A double microelectrode setup was used to simultaneously record from two neurons separated by distances as small as 250 micrometer. In the six patients who had limb tremor during the recording session (n = 76 pairs), the discharge pattern of 12 pairs of tremor cells (TCs) was found to be coherent at the frequency of the limb tremor. Both in-phase and out-of-phase relationships were observed between TCs. Interestingly, in these six patients, 63/129 single neurons displayed 15-30 Hz oscillations, whereas 36/76 pairs were coherent in this frequency range. Although the oscillatory frequencies were variable between patients, they were highly clustered within a patient. The phase difference between these pairs was found to be close to 0. High-frequency synchronization was observed during periods of limb tremor as well as during intermittent periods with no apparent limb tremor. In contrast, in the three patients without limb tremor during the recording session, only 1/84 neurons had high-frequency oscillatory activity, and no TCs or synchronous high-frequency oscillatory activity was observed (n = 45 pairs). These findings demonstrate that in PD patients with limb tremor, many STN neurons display high-frequency oscillations with a high degree of in-phase synchrony. The results suggest that high-frequency synchronized oscillatory activity may be associated with the pathology that gives rise to tremor in PD patients.

Action Potentials↗
PubMed2000

Long-term follow-up of unilateral pallidotomy in advanced Parkinson's disease.

BACKGROUND: Although the short-term benefits of posteroventral pallidotomy for patients with advanced Parkinson's disease have been well documented, little is known about the long-term outcome of the procedure. METHODS: We conducted a long-term follow-up study of a cohort of 40 patients who had undergone unilateral posteroventral medial pallidotomy between 1993 and 1996. Twenty patients were not evaluated because they had undergone a second surgical procedure (11 patients) or had died (2) or because they had dementia or another debilitating illness (4), lived too far away (1), or had been lost to follow-up (2). We conducted serial postoperative assessments of parkinsonism in the remaining 20 patients while they were taking medications ("on" period) and after overnight withdrawal of the drugs ("off" period). The mean follow-up time was 52 months (range, 41 to 64). RESULTS: The combined off-period score for activities of daily living and motor function on the Unified Parkinson's Disease Rating Scale was 18.0 percent better at the last evaluation than at base line (95 percent confidence interval, 4.9 to 31.0 percent; P=0.01). Significant improvements were also evident in the off-period scores for contralateral tremor (65.4 percent improvement, P=0.007), rigidity (43.2 percent, P=0.03), and bradykinesia (18.2 percent, P=0.04) and in the on-period score for contralateral dyskinesia (70.6 percent, P<0.001). Changes in medication did not contribute to the sustained improvement. The 20 patients who could not be included in the long-term analysis had similar base-line characteristics but a worse response to surgery at six months. CONCLUSIONS: In the group of patients with advanced Parkinson's disease who could be enrolled in our long-term follow-up study of unilateral posteroventral medial pallidotomy (20 patients from the original cohort of 40), significant early improvements in off-period contralateral signs of parkinsonism were sustained for up to five and a half years. There was a sustained significant improvement in on-period contralateral dyskinesia but not in other on-period signs of parkinsonism.

Activities of Daily Living↗
PubMed2000

An investigation of the effects of subthalamic nucleus stimulation on acoustic measures of voice.

Seven patients with Parkinson's disease were implanted with deep brain stimulators to provide chronic electrical stimulation to the subthalamic nucleus bilaterally. Acoustic recordings and neurologic assessments were undertaken before surgery in the medication-off and medication-on conditions and after surgery with and without electrical stimulation in the medication-off and medication-on conditions. The data showed significant improvements in limb motor performance in response to medication before surgery and when the subthalamic nucleus was stimulated after surgery. Six months after surgery, there were small but statistically significant increases in sound pressure level and fundamental frequency variability in response to stimulation in the medication-on condition. No other statistically significant speech changes were measured. These findings are consistent with several other studies that have reported disparity between limb and speech improvements after neurosurgical intervention for Parkinson's disease.

Adult↗
PubMed2000

Neuropsychological outcome of GPi pallidotomy and GPi or STN deep brain stimulation in Parkinson's disease.

This paper highlights the neuropsychological sequelae of posteroventral pallidotomy (PVP) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) at 3/6 months postoperatively. Results are based on our extensive experience with PVP and our preliminary observations with DBS. Patients with borderline cognitive or psychiatric functioning risk postoperative decompensation. Nonlateralizing attentional and hemisphere-specific impairments of frontostriatal cognitive functions followed unilateral PVP. "Frontal" behavioral dyscontrol was observed in approximately 25% of patients. Three cases of staged bilateral PVP suggest that premorbid factors may predict outcome, although lesion size and location are also critical. Older patients are at risk for significant cognitive and behavioral decline after bilateral STN DBS, while GPi DBS may be safer.

Adult↗
PubMed2000

Stereotactic surgery for temporal lobe epilepsy.

In light of the recent resurgence of interest in stereotactic functional procedures, the authors have reviewed the role of stereotactic ablative surgery in the treatment of temporal lobe epilepsy. Literature pertaining to stereotactic amygdalotomy, hippocampotomy and fornicotomy is reviewed and summarized. However, the results presented in those early studies are difficult to interpret given the surgical techniques and outcome assessment used. Modern stereotactic ablative surgery using current image-guided technology offers the opportunity to revisit some of these techniques. In recent studies of stereotactic amygdalohippocampotomy, outcomes are not as favorable as those obtained with standard temporal resections. However, these relatively discrete ablative techniques may shed light on the anatomical substrate underlying temporal lobe epilepsy.

Amygdala↗
PubMed2000

Advances in neurostimulation for movement disorders.

In just 12 years since its introduction, deep brain stimulation (DBS) has become well established as a safe and effective therapy in the treatment of medically refractory movement disorders. Ventralis intermedius (Vim) DBS has virtually replaced thalamotomy in the routine clinical treatment of essential tremor, affording relief to thousands of patients who previously would not have undergone surgery, and there is increasing usage of Vim DBS in other tremors of intention (e.g., multiple sclerosis). Subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS have revolutionized the treatment of advanced stage Parkinson's disease, improving all cardinal disease features and increasing 'on' time without dyskinesias. Finally, DBS of various sub-cortical structures is being developed and tested in other less prevalent movement disorders such as dystonia. Future developments in this rapidly advancing area will no doubt include widening indications for this relatively safe surgical procedure, elucidation of the mechanisms of action of electrical stimulation, and technological advancements improving effectiveness and convenience.

Brain↗