andres lozano | University of Toronto (original) (raw)

Papers by andres lozano

Experimental Brain …, 2008

The lancet. Psychiatry, 2015

Expert review of neurotherapeutics, 2015

The subthalamic nucleus (STN) has been a major target of deep brain stimulation (DBS) for Parkins... more The subthalamic nucleus (STN) has been a major target of deep brain stimulation (DBS) for Parkinson's disease (PD) over the past 20 years. The benefits of DBS of the STN include: decreased motor fluctuations and bradykinesia, tremor reduction and a reduction in dopaminergic drug requirements and dyskinesias. Despite these overall positive effects, the outcomes of STN DBS can be variable, contributing to the debate over the best DBS target for PD. Here, the authors review the current practice of STN DBS and also review both the existing and emerging technologies that are likely to improve the accuracy and effectiveness of STN DBS for PD. The authors emphasize patient selection, accuracy of electrode placement within the brain and the selection of appropriate stimulation parameters to optimize clinical benefits.

NeuroImage, Jan 23, 2015

Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate regio... more Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS. Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the "micro-lesion" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry. The DBS group de...

Journal of Neurology, Neurosurgery & Psychiatry, 2015

The effect of the variability of electrode placement on outcomes after bilateral deep brain stimu... more The effect of the variability of electrode placement on outcomes after bilateral deep brain stimulation of subthalamic nucleus has not been sufficiently studied, especially with respect to the sequence of hemisphere implantation. We retrospectively analysed the clinical and radiographic data of all the consecutive patients with Parkinson&amp;amp;amp;#39;s disease who underwent surgery at our centre and completed at least 1 year follow-up. The dispersion in electrode location was calculated by the square of deviation from population mean, and the direction of deviation was analysed by comparing the intended and final implantation coordinates. Linear regression analysis was performed to analyse the predictors of postoperative improvement of the motor condition, also controlling for the sequence of implanted hemisphere. 76 patients (mean age 58±7.2 years) were studied. Compared with the first side, the second side electrode tip had significantly higher dispersion as an overall effect (5.6±21.6 vs 2.2±4.9 mm(2), p=0.04), or along the X-axis (4.1±15.6 vs 1.4±2.4 mm(2), p=0.03) and Z-axis (4.9±11.5 vs 2.9±3.6 mm(2), p=0.02); the second side stimulation was also associated with a lower threshold for side effects (contact 0, p&amp;amp;amp;lt;0.001 and contact 3, p=0.004). In the linear regression analysis, the significant predictors of outcome were baseline activities of daily living (p=0.010) and dispersion of electrode on the second side (p=0.005). We observed a higher dispersion for the electrode on the second implanted side, which also resulted to be a significant predictor of motor outcome at 1 year.

Epilepsia, 2015

The feasibility of automated detection of cortical-onset epileptic seizures from subcortical stru... more The feasibility of automated detection of cortical-onset epileptic seizures from subcortical structures such as the thalamus was investigated via simultaneous recording of electroencephalography (EEG) and anterior and centromedian thalamic nuclei electrical signals (electrothalamography) in nine subjects with pharmacoresistant seizures admitted to an epilepsy monitoring unit after deep brain stimulating electrode implantation. Thalamic electrical signals were analyzed using a validated seizure detection algorithm, and times of seizure onset and termination were compared to those determined through visual analysis of video-EEG. Ictal activity was recorded from the scalp and thalamic nuclei in three subjects who had seizures during the 3-4-day recording period. In the majority of seizures, ictal activity in the thalamic nuclei preceded electrographic onset as determined from the EEG or clinical onset as determined from behavioral observations. Interictal epileptiform discharges were also recorded from the thalamus and in certain instances had no scalp representation. Subcortical/thalamic detection of cortical-onset seizures is feasible. This approach would enable contingent therapy delivery and may be particularly valuable for subjects with multiple or difficult-to-localize epileptogenic regions.

Journal of neurosurgery, Jan 26, 2015

OBJECT Recent works have assessed academic output across neurosurgical programs using various ana... more OBJECT Recent works have assessed academic output across neurosurgical programs using various analyses of accumulated citations as a proxy for academic activity and productivity. These assessments have emphasized North American neurosurgical training centers and have largely excluded centers outside the United States. Because of the long tradition and level of academic activity in neurosurgery at the University of Toronto, the authors sought to compare that program's publication and citation metrics with those of established programs in the US as documented in the literature. So as to not rely on historical achievements that may be of less relevance, they focused on recent works, that is, those published in the most recent complete 5-year period. METHODS The authors sought to make their data comparable to existing published data from other programs. To this end, they compiled a list of published papers by neurosurgical faculty at the University of Toronto for the period from 200...

Neurology, 2015

To evaluate changes in the diagnosis of Axis I psychiatric disorders in patients with primary and... more To evaluate changes in the diagnosis of Axis I psychiatric disorders in patients with primary and secondary dystonia after deep brain stimulation (DBS) of the globus pallidus internus (GPi). Structured Clinical Interviews for the DSM-IV, Axis I psychiatric disorders, were prospectively performed before and after surgery. Diagnoses were made based on DSM-IV criteria. Psychiatric disorders were grouped into 5 categories: mood, anxiety, addiction, obsessive-compulsive disorders, and psychosis. Patients could be stratified to more than one category. Rates for unchanged diagnoses, diagnoses in remission, and new-onset diagnoses after surgery for each category were calculated. Fifty-seven patients with primary and secondary dystonia were included. Mean ± SD age at surgery and dystonia duration at time of surgery was 50.6 ± 13.8 and 19.0 ± 13.2 years, respectively. Preoperatively, 37 Axis I diagnoses were made in 25 patients, 43.8% of those presenting with at least 1 Axis I diagnosis (mostly mood and anxiety disorders). Mean ± SD duration of psychiatric follow-up was 24.4 ± 19.6 months. Overall, after surgery no significant changes (p = 0.16) were found in Axis I diagnoses (23 patients, 40.3%): 27 (73%) unchanged, 10 (27%) in complete remission, and 4 (12.9%) new-onset diagnoses. Our results support the overall psychiatric stability of patients with primary and secondary dystonia treated with GPi DBS. However, considering the high psychiatric morbidity in the dystonia population, psychiatric assessments before and after surgery are strongly recommended. This study provides Class IV evidence that GPi DBS does not change Axis I psychiatric diagnoses in patients with primary and secondary dystonia.

Neurosurgical Focus, 2015

The European journal of neuroscience, Jan 25, 2015

Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucl... more Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus (STN) deep brain stimulation (DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesized that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analyzed microelectrode recording (MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER, 27 cells from 7 patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analyzed using the Kaneoke-Vitek methodology and local field potential (LFP) oscillatory activity was also interrogated. Dexmedetomidine was associat...

Annals of neurology, Jan 10, 2015

A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AA... more A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra. We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-mo...

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000

It has been hypothesized that in Parkinson's disease (PD) there is increased synchronization ... more 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 withi...

Proceedings of the National Academy of Sciences of the United States of America, Jan 14, 2014

Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditio... more Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive...

Brain : a journal of neurology, 2014

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a v... more Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive a...

Stereotactic and functional neurosurgery, 2012

Functional neurosurgery is a rapidly expanding field, with an exponentially growing literature. H... more Functional neurosurgery is a rapidly expanding field, with an exponentially growing literature. However, as with other fields, it can sometimes be difficult to distinguish between what is incremental and what is transformational. One way of measuring durable impact is examining the number of times a specific piece of scholarship is cited by others in the field. For example, papers that have been cited at least 400 times are designated 'citation classics' or works that, by virtue of very high citations, have been deemed of particular importance by researchers working in related disciplines. We queried a large, web-based scholarly database using 49 pre-selected search terms. The results for each individual query was manually examined for relevance to the functional neurosurgery field in order to arrive at the top 100 most highly cited papers as well as the citation classics. The top 100 most cited papers, including 61 citation classics, in the stereotactic and functional neuro...

Advances in neurology, 2003

Stereotactic and functional neurosurgery, 1995

Failed stereotactic biopsy is one in which a definitive histological or microbiological diagnosis... more Failed stereotactic biopsy is one in which a definitive histological or microbiological diagnosis is not achieved based on the tissue obtained. Of 518 consecutive CT-guided stereotactic biopsies of intra-axial mass lesions, 42 (8.1%) cases were failed biopsies. Inflammatory changes were seen in 10 cases (24%); gliosis was seen in 11 cases (26%); 9 cases (21%) yielded necrotic specimens; normal brain was retrieved in 7 cases (17%); blood/hemorrhagic brain was seen in 3 cases and in 2 cases, no tissue could be obtained. Variables that significantly influenced the diagnostic success included the immune status (HIV positive; p < 0.001). The complication rate in the failed biopsy group was significantly higher. The subsequent management and outcome of patients who suffered a failed stereotactic biopsy are discussed.