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Biomedical subjects

Andres M Lozano

Publications and source records attributed to Andres M Lozano.

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

Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy.

OBJECTIVE: To investigate the neurophysiological characteristics and prognostic impact of EEG synchronization with low frequency thalamic stimulation in patients with intractable epilepsy. METHODS: Electrical stimuli were delivered through deep brain stimulating (DBS) electrodes at 2, 5 or 10Hz to the anterior nucleus (AN) and the dorsomedial nucleus (DM) of six patients using the implanted programmable stimulation device. EEGs were recorded from 27 scalp electrodes. "Modeled" responses for 5 and 10Hz stimulation were computed based on the cerebral responses (CRs) evoked by "single pulse" (2Hz) stimulation and compared with the recorded EEG results. RESULTS: Rhythmic cortical 5Hz EEG synchronization occurred in 4/6 patients, with stimulation at 6/11 AN and 5/11 DM sites. Three of four patients with synchronization, but neither of the two patients without, had a significant reduction in seizure frequency. The magnitude of 5 and 10Hz EEG synchronization was positively related to the amplitudes of "single pulse" CRs. Simple temporal superposition of "single pulse" CRs resulted in "modeled" responses with strikingly similar morphology and scalp voltage distribution. CONCLUSIONS: Rhythmic EEG synchronization with low frequency stimulation primarily reflects spatiotemporal summation (interference) of "single pulse" CRs. SIGNIFICANCE: Rhythmic EEG synchronization might not serve as a physiologic verification of optimal localization of DBS electrodes. Its usefulness for the prediction of clinical efficacy is questionable.

Adult↗
PubMed2006

Subthalamic nucleus stimulation: improvements in outcome with reprogramming.

BACKGROUND: Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE: To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through "hands-on" involvement of a neurologist expert in both movement disorders and DBS programming. METHODS: In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean +/- SD, 3.5 +/- 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS: In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS: Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.

Antiparkinson Agents↗
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

Depth electrode recorded cerebral responses with deep brain stimulation of the anterior thalamus for epilepsy.

OBJECTIVE: We investigated the relation between anterior thalamic stimulation and the morphology of the evoked cerebral responses (CRs) using intracerebral depth electrodes in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Monopolar cathodic and bipolar stimuli were delivered at a rate of 2 or 1 Hz to the anterior nucleus (AN) and the dorsomedian nucleus (DM) of two patients using the programmable stimulation device (Medtronic ITREL II) or a GRASS stimulation device (S12). CRs were recorded from depth or DBS electrodes, situated bilaterally in mesial temporal (hippocampus, both patients), lateral temporal (one patient), orbitofrontal (Brodmann area 11, one patient) and anterior thalamic sites (one patient). RESULTS: The distribution and morphology of the CRs depended primarily on the site of stimulation within the anterior thalamic region. Overall, monopolar cathodic and bipolar stimulation of the AN elicited CRs mainly in ipsilateral mesial temporal cortical areas, whereas stimulation of the DM evoked high-amplitude CRs predominantly in ipsilateral orbitofrontal areas. The amplitude of the CR was positively related to the strength of the stimulus and generally higher with monopolar than with bipolar stimulation. The differences between CRs elicited during wakefulness or slow wave sleep were minimal. CONCLUSIONS: The distribution of the CRs corresponded with the intracerebral pathways of the involved structures and the findings are in good accordance with those of our previous study investigating the sources of CRs using statistical non-parametric mapping of low resolution electromagnetic tomography (LORETA) values. SIGNIFICANCE: Our findings indicate a certain degree of point-to-point specificity within the thalamocortical circuitry, which may make optimal localization of DBS electrodes important in patients with epilepsy.

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

Deep brain stimulation: postoperative issues.

Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Bacterial Infections↗
PubMed2006

Novel surgical therapies for Tourette syndrome.

Tourette syndrome is a common neurologic disorder with close ties to obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The majority of patients improve spontaneously as they near adulthood. Most others are effectively treated with pharmacologic agents, although these therapies fail for an unfortunate few. For patients debilitated by the disease despite medical therapy, surgery can become an important option.

Brain↗
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↗
PubMed2006

Neural stimulation for Parkinson's disease: current therapies and future directions.

Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Brain↗
PubMed2005

Cortical activation with deep brain stimulation of the anterior thalamus for epilepsy.

OBJECTIVE: We studied the relation between thalamic stimulation parameters and the morphology, topographic distribution and cortical sources of the cerebral responses in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Bipolar and monopolar stimuli were delivered at a rate of 2 Hz to the anterior (AN, four patients), the dorsomedian (DM, four patients), and the centromedian nucleus (CM, one patient) using the programmable stimulation device (Medtronic ITREL II). Source modeling was carried out by using statistical non-parametric mapping of low-resolution electromagnetic tomography (LORETA) values. RESULTS: All patients demonstrated reproducible time-locked cortical responses (CRs) consisting of a sequence of components with latencies between 20 and 320 ms. The morphology of these CRs, however, was very heterogeneous, depending primarily on the site of stimulation. Following AN stimulation, cortical activation was most prominent in ipsilateral cingulate gyrus, insular cortex and lateral neocortical temporal structures. Stimulation of the DM mainly showed activation of the ipsilateral orbitofrontal and mesial and lateral frontal areas, but also involvement of mesial temporal structures. Stimulation of the CM showed a rather diffuse (though still mainly ipsilateral) increase of cortical activity. The magnitude of cortical activation was positively related to the strength of the stimulus and inversely related to the impedance of the electrode. CONCLUSIONS: The pattern of cortical activation corresponded with the hodology of the involved structures and may underscore the importance of optimal localization of DBS electrodes in patients with epilepsy. SIGNIFICANCE: The method of analyzing sources of CRs could potentially be a useful tool for titration of DBS parameters in patients with electrode contacts in clinically silent areas. Furthermore, the inverse relation of the cortical activation and the impedance of the electrode contacts might suggest that these impedance measurements should be taken into consideration when adjusting DBS parameters in patients with epilepsy.

Adult↗
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

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress.

Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1-/-embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.

Animals↗
PubMed2005

Deep brain stimulation for treatment-resistant depression.

Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.

Adult↗