Biomedical subjects

A M Lozano

Publications and source records attributed to A M Lozano.

At least 55 records · Page 3Linked to original sources

PubMed2000

Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease.

The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 +/- 8 years, years with Parkinson's disease = 15 +/- 3, verbal IQ = 114 +/- 12) were evaluated (in their best 'on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3-6 months (n = 11) and at 9-12 months (n =10) post-operatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3-6 months post-operative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. 'Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9-12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.

Affect↗

PubMed2000

Relationship of lesion location to cognitive outcome following microelectrode-guided pallidotomy for Parkinson's disease: support for the existence of cognitive circuits in the human pallidum.

Current models of basal ganglia anatomy posit the existence of multiple parallel, anatomically segregated circuits. Anatomical data from non-human primates suggest that the circuits subserving motor functions are segregated from those subserving cognitive functions. Here we present data that demonstrate that, in humans, motor and cognitive frontosubcortical circuits are segregated. We studied a group of patients with Parkinson's disease undergoing surgical lesioning of the globus pallidus internus for relief of their symptoms. Lesion location along an anteromedial-to-posterolateral axis was found to be related to postsurgical outcome on both cognitive and motor measures. Performance on several neuropsychological measures, including the generation of category exemplars and continuous mental addition, was linearly related to distance along this axis, with anteromedial lesions leading to postsurgical impairment, intermediate lesions having little effect and posterolateral lesions leading to an improvement on several measures. The same relationship was found between memory performance under conditions of proactive interference and lesion location within the globus pallidus internus. In contrast, bradykinesia, assessed as the speed of finger-tapping, had a non-linear relationship to lesion location, intermediate lesions leading to greater postsurgical improvement than lesions in more extreme anteromedial or posterolateral locations. These data demonstrate that the cognitive effects of pallidotomy can be dissociated from the motor effects. These effects depend upon the placement of the lesions within the globus pallidus internus, supporting the segregation of functionally distinct circuits in the human pallidum.

Cognition↗

PubMed2000

The pedunculopontine nucleus and Parkinson's disease.

Akinesia and gait disturbances are particularly incapacitating for patients with Parkinson's disease. The anatomical and physiological substrates for these disturbances are poorly understood. The pedunculopontine nucleus (PPN) is thought to be involved in the initiation and modulation of gait and other stereotyped movements, because electrical stimulation and the application of neuroactive substances in the PPN can elicit locomotor activity in experimental animals. Glutamatergic neurones of the PPNd (pars dissipatus) are thought to be important regulators of the basal ganglia and spinal cord. The other component of the PPN, the cholinergic pars compacta (PPNc), is a principal component in a feedback loop from the spinal cord and limbic system back into the basal ganglia and thalamus. Electrophysiological studies suggest that 'bursting' glutamatergic PPNd neurones are related to the initiation of programmed movements while non-bursting cholinergic PPNc neurones are related to the maintenance of steady-state locomotion. Furthermore, since patients with Parkinson's disease have significant loss of PPN neurones and experimental lesions in the PPN of normal monkeys result in akinesia, the degeneration of PPN neurones or their dysfunction may be important in the pathophysiology of locomotor and postural disturbances of parkinsonism. The goal of this review is (i) to highlight the anatomical connections and physiological attributes of the PPN, (ii) to discuss how the function of these connections may be altered in the parkinsonian state, and (iii) to speculate how present and potential future therapy directed to the PPN might improve akinesia and gait difficulties in parkinsonian patients.

Animals↗

PubMed2000

Central nystagmus induced by deep-brain stimulation for epilepsy.

PURPOSE: The goal of the present study was to describe the localization of central nystagmus induced as a side effect of electrical deep-brain stimulation for epilepsy. METHODS: Bilateral deep-brain stimulating electrodes were inserted in the centromedian nucleus of the thalamus to control seizures in a patient with intractable epilepsy. RESULTS: Cathodal high-frequency stimulation through the deepest contact of each electrode elicited cycles of slow ipsiversive conjugate eye deviations, each followed by rapid contralateral jerks. The involved electrode contacts were situated at the mesodiencephalic junction just inferior to the centromedian nucleus of the thalamus and rostral to the superior colliculus. Right-sided stimulation evoked left beating nystagmus and left-sided stimulation evoked right beating nystagmus. Stimulation through other electrode contacts did not induce nystagmus. Electronystagmography showed the nystagmus to have constant velocity slow phases. CONCLUSIONS: A central nystagmogenic area exists in humans that appears to be homologous to the nucleus of the optic tract, a region described in nonhuman primates to play a role in the generation of optokinetic nystagmus.

Adult↗

PubMed2000

Human anterior cingulate cortex neurons modulated by attention-demanding tasks.

Recent imaging studies have implicated the anterior cingulate cortex (ACC) in various cognitive functions, including attention. However, until now, there was no evidence for changes in neuronal activity of individual ACC neurons during performance of tasks that require attention and effortful thought. We hypothesized these neurons must exist in the human ACC. In this study, we present electrophysiological data from microelectrode single neuron recordings in the human ACC of neuronal modulation during attention-demanding tasks in 19% of 36 neurons tested. These findings provide the first direct evidence of an influence of a cognitive state on the spontaneous neuronal activity of human ACC neurons.

Adult↗

PubMed2000

Microstimulation-induced inhibition of neuronal firing in human globus pallidus.

Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectively reduce L-dopa-induced dyskinesias and bradykinesia, but the mechanisms are unknown. The present study examined the effects of microstimulation in GPi on the activity of neurons close to the stimulation site. Recordings were made from GPi using two fixed or independently controlled microelectrodes, with the electrode tips usually approximately 250 or >600 micrometer apart in PD patients undergoing stereotactic exploration to localize the optimal site for placement of a lesion or DBS electrode. The spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three patients was inhibited by microstimulation at currents typically <10 microA (0.15-ms pulses at 5 Hz). The inhibition had a duration of 10-25 ms at threshold. These findings suggest that microstimulation within GPi preferentially excites the axon terminals of striatal and/or external pallidal neurons causing release of GABA and inhibition of GPi neurons.

Action Potentials↗

PubMed2000

Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study.

OBJECT: Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS. METHODS: The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas. CONCLUSIONS: The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.

Adult↗

PubMed2000

Neuronal recordings in Parkinson's disease patients with dyskinesias induced by apomorphine.

Dopaminergic agents reverse parkinsonism but commonly induce dyskinesia in patients with Parkinson's disease (PD) on long-term levodopa therapy. The aim of this study was to determine the neurophysiologic correlates of the amelioration of parkinsonism and the involuntary movements produced by the dopamine agonist apomorphine. Seventeen PD patients were given apomorphine (2-6 mg) before surgery. Neural activity was recorded for individual neurons and for populations of neurons before and after apomorphine. Both internal (GPi) and external (GPe) segments of the globus pallidus were sampled in patients undergoing pallidal surgery. The subthalamic nucleus (STN) was sampled in STN surgery patients. Results suggest that dopaminergic agents act by decreasing GPi and STN activity, and increasing GPe activity, and that drug-induced dyskinesias results from a large reduction in GPi firing.

Action Potentials↗

PubMed2000

Targeting the basal ganglia for deep brain stimulation in Parkinson's disease.

The revitalization of surgery for Parkinson's disease (PD) has fueled discussion about the best methodology to define the target. Placement of electrodes for deep brain stimulation (DBS) requires the usual stereotactic technique but the argument is mainly centered on whether or not microrecording neuronal activity is necessary. We compared the accuracy of calculating the coordinates X (medio-lateral) and Y (rostro-caudal) considered by the classic stereotactic method, i.e., definition of the AC-PC intercomissural line by MRI and a digitized version of the Schaltenbrand's atlas, with final electrode placement according with microrecording and microstimulation in 21 patients. For both the globus pallidum internum (GPi) (n = 21) and the subthalamic nucleus (STN) (n = 36) there was, respectively, a 43% and 45% mismatching of more than 3 mm between the theoretic coordinates and the final site of electrode location. This applies to both the X and Y planes. Accuracy was not improved in patients (n = 11) in whom the bilateral procedure was undertaken in a single day. We conclude that proper electrode positioning of the STN and GPi requires fine electrophysiologic assessment.

Adult↗

PubMed2000

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

Adult↗

PubMed1999

Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation.

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in a patient with severe idiopathic generalized dystonia resulted in immediate improvement of all aspects of dystonia. During joystick movement, GPi DBS reduced PET activation bilaterally in the primary motor, lateral premotor, supplementary motor, anterior cingulate, and prefrontal areas and ipsilaterally in the lentiform nucleus. Altering basal ganglia function with GPi DBS reverses the overactivity of certain motor cortical areas present in dystonia.

Brain↗

PubMed1999

Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation.

OBJECTIVE: To compare the effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) with bilateral STN DBS in advanced PD. METHODS: Our initial 10 consecutive patients with medication-refractory motor fluctuations and levodopa-induced dyskinesias undergoing chronic bilateral STN DBS underwent a standardized evaluation of unilateral and bilateral STN DBS in the medication-off state 6 to 18 months after electrode implantation. RESULTS: Bilateral STN DBS improved the mean total Unified Parkinson's Disease Rating Scale motor score by 54%, whereas unilateral stimulation improved motor scores only 23%. Unilateral STN DBS improved postural stability and gait 14%, other axial motor features 19%, and overall parkinsonism in limbs contralateral to stimulation by 46%, including an 86% improvement in contralateral tremor. However, bilateral STN DBS resulted in greater improvement in each of these domains, including limb function, i.e., the reduction in scores from the limbs on one side was greater with bilateral than with unilateral stimulation of the contralateral STN. CONCLUSIONS: Bilateral STN DBS improves parkinsonism considerably more than unilateral STN DBS; bilateral simultaneous electrode implantation may be the most appropriate surgical option for patients with significant bilateral disability. Unilateral STN DBS results in moderate improvement in all aspects of off-period parkinsonism and improves tremor as much as is typically reported with DBS of the ventral intermedius nucleus of the thalamus (Vim). For this reason, STN DBS may be a more appropriate choice than Vim DBS or thalamotomy for parkinsonian tremor. Some patients with highly asymmetric tremor-dominant PD might be appropriately treated with unilateral instead of bilateral STN DBS.

Aged↗

PubMed1999

Neuronal age influences the response to neurite outgrowth inhibitory activity in the central and peripheral nervous systems.

Axonal regeneration is abortive in the central nervous system (CNS) of adult mammals, but readily occurs in the injured peripheral nervous system (PNS). Recent experiments indicate an important role for both intrinsic neuronal features and extrinsic substrate properties in determining the propensity for axonal regrowth. In particular, certain components of adult mammalian CNS myelin have been shown to exert a strong inhibitory influence on neurite outgrowth. To determine whether the potent neurite outgrowth inhibitory activity found in CNS myelin may also be present in PNS myelin and to study the influence of neuronal age on neurite outgrowth, we used a cryoculture assay in which dissociated rat dorsal root ganglion (DRG) neurons of different ages were challenged to extend neurites on fractionated myelin and cryostat sections from the PNS (sciatic nerve and myelin-free degenerated sciatic nerve) and CNS (optic nerve) of adult rats. The CNS environment of the optic nerve did not support E17 to P8 DRG neurite adhesion or outgrowth. E17 DRG neurons, unlike their older counterparts, however, were able to attach and extend neurites onto normal sciatic nerve and onto purified PNS myelin. In contrast, a vigorous neurite outgrowth response from all the ages tested was observed on the myelin-free degenerated sciatic nerve. These results indicate that PNS myelin is a potent inhibitor of neurite outgrowth and that DRG neuronal age plays an important role in determining the propensity for neurite outgrowth and regenerative response on inhibitory PNS and CNS substrata.

Animals↗

PubMed1999

Tremor arrest with thalamic microinjections of muscimol in patients with essential tremor.

Six patients undergoing stereotactic procedures for essential tremor received microinjections of muscimol (a gamma-aminobutyric acid-A [GABA(A)] agonist) into the ventralis intermedius thalamus in areas where tremor-synchronous cells were identified electrophysiologically with microelectrode recordings and where tremor reduction occurred with electrical microstimulation. Injections of muscimol but not saline consistently reduced tremor in each patient. The effect had a mean latency of 7 minutes and lasted an average of 9 minutes. We propose that GABA-mediated thalamic neuronal inhibition may represent a mechanism underlying the effectiveness of surgery for tremor and that GABA analogues could potentially be used therapeutically.

Aged↗

PubMed1999

Posteroventral medial pallidotomy in Parkinson's disease.

There has been a resurgence in the use of functional neurosurgery for Parkinson's disease. An important factor that has played a role in this development is the recent understanding of the functional anatomy of the basal ganglia including a knowledge of the changes in the activities of neurons in the internal segment of the globus pallidus (Gpi) and the subthalamic nucleus (STN) in Parkinson's disease as well as the knowledge of the presence of segregated functional loops within the basal ganglia which include a sensory-motor loop that involves the posteromedial globus pallidus rather than the anterior GPi where earlier pallidotomy lesions had been made. Laitinen reintroduced the modern posteroventral medial pallidotomy (PVMP) in 1992. Since then it has become clear that this treatment has major effects on levodopa-induced dyskinesias and, unlike Vim thalamotomy, improves bradykinesia and rigidity as well as tremor. In this report, we review a number of topics related to PVMP including the clinical results of pallidotomy available in the literature as well as an update of our own 2 year follow-up data, studies evaluating factors that might predict the subsequent response to pallidotomy, the neuropsychological effects of the procedure, results of imaging studies including the correlation of clinical effects with lesion location, the question of bilateral pallidotomy and pallidotomy combined with deep brain stimulation and finally whether PVMP is effective in other parkinsonian disorders.

Globus Pallidus↗

PubMed1999

Mechanism of the silent period following transcranial magnetic stimulation. Evidence from epidural recordings.

We investigated the nature of the silent period (SP) following transcranial magnetic stimulation by recording corticospinal volleys in a patient with implanted cervical epidural electrodes. Single suprathreshold test stimuli and paired stimuli at interstimulus intervals (ISIs) of 50-200 ms were delivered while the subject maintained a constant background contraction. The silent period duration from a single test stimulus was 357+/-62 ms. The test motor-evoked potentials were markedly reduced at all the ISIs tested. The I (indirect) waves induced by the test stimulus were largely unchanged at an ISI of 50 ms, suggesting that there was little change in motor cortex excitability. However, the corticospinal volleys, especially the late I waves, were substantially reduced at ISIs of 100 ms, 150 ms, and 200 ms. Our findings suggest that the early part of the SP is mainly due to spinal mechanisms, while the late part of the SP is related to reduced motor cortex excitability.

Accidents, Traffic↗

PubMed1999

A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients.

Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical procedures for the treatment of pain and movement disorders. Burst indices (the number of bursting cells per electrode track) were computed for all the explorations in the two groups. The burst indices in the pain and non-pain groups (1.73 +/- 0.28 and 1.14 +/- 0.16, respectively) were not significantly different from each other. The bursts were analyzed to see if they fulfilled the criteria of low-threshold calcium spike (LTS)-evoked bursts characterized by (i) a shortening of the first interspike interval with an increase in the number of interspike intervals in the burst and also (ii) a progressive prolongation of successive interspike intervals. LTS-evoked bursts were identified in 27/47 (57%) bursting cells in pain patients and 15/32 (47%) cells in non-pain patients. These data demonstrate that the occurrence of bursting activity and of LTS-evoked bursts in the human thalamus is prevalent in both pain and non-pain patients. This suggests that the bursting activity of thalamic neurons in pain patients is not necessarily related to the occurrence of their pain.

Action Potentials↗

PubMed1999

On the focal nature of inhibition and facilitation in the human motor cortex.

OBJECTIVE: To find the area of the human cortex from which inhibition and facilitation of corticospinal neurons could be obtained. METHODS: A patient with seizures had an array of 64 electrodes placed over the left fronto-temporal cortex. The motor evoked potential (MEP) elicited by stimulating through one pair of electrodes was conditioned by stimuli that were subthreshold for a MEP given through adjacent pairs of electrodes. RESULTS: The MEP recorded over the right abductor pollicis brevis produced by stimulating over the hand area of the left cortex could be inhibited (at intervals less than 5 ms) and facilitated (at intervals greater than 5 ms) by subthreshold conditioning stimuli delivered through neighbouring pairs of electrodes. The inhibition and facilitation were only obtained when the conditioning stimuli were delivered within 1-2 cm of the test site. The sites producing inhibition and facilitation were not identical. Conditioning stimuli over the face area did not inhibit the MEP produced by stimulating the hand area or vice versa. CONCLUSION: The inhibition and facilitation of corticospinal neurons projecting to a given muscle arise from small areas close to those corticospinal neurons.

Electric Stimulation↗