Deep Brain Stimulation Site Research Articles

Mapping Lesion-Related Human Aggression to a Common Brain Network

BackgroundAggression exacts a significant toll on human societies and is highly prevalent among neuropsychiatric patients. The neural mechanisms of aggression are unclear and treatment options are limited. MethodsUsing a recently validated lesion network mapping technique, we derived an aggression-associated network by analyzing data from 182 patients who had experienced penetrating head injuries during their service in the Vietnam War. To test whether damage to this lesion-derived network would increase the risk of aggression-related neuropsychiatric symptoms, we used the Harvard Lesion Repository (N = 852). To explore potential therapeutic relevance of this network, we used an independent deep brain stimulation dataset of 25 patients with epilepsy, in which irritability and aggression are known potential side effects. ResultsWe found that lesions associated with aggression occurred in many different brain locations but were characterized by a specific brain network defined by functional connectivity to a hub region in the right prefrontal cortex. This network involves positive connectivity to the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, frontal pole, posterior cingulate cortex, anterior cingulate cortex, temporal-parietal junction, and lateral temporal lobe and negative connectivity to the amygdala, hippocampus, insula, and visual cortex. Among all 24 neuropsychiatric symptoms included in the Harvard Lesion Repository, criminality demonstrated the most alignment with our aggression-associated network. Deep brain stimulation site connectivity to this same network was associated with increased irritability. ConclusionsWe conclude that brain lesions associated with aggression map to a specific human brain circuit, and the functionally connected regions in this circuit provide testable targets for therapeutic neuromodulation.

Mapping Lesion-Related Epilepsy to a Human Brain Network

It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Epilepsy or no epilepsy. Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

Neuronal Quantification of Subthalamic Nucleus in Adult Human Cadaveric Brain- A Histological Study

Introduction: The Subthalamic Nucleus (STN) has emerged as a preferred target site for deep brain stimulation for various neurological disorders. There is scarcity of literature on the internal structure of subthalamic nucleus. Aim: To study its microanatomy and quantification of its various cells in different age groups. Materials and Methods: The study design of the current study is of cross-sectional type which was done on 30 cadaveric brains in Anatomy department of Lady Hardinge medical college, New Delhi which were divided into three age groups ranging from 20 to &gt;50 years. The subthalamic nucleus was fixed and subjected to standard tissue processing procedure. The sections were stained with Haematoxylin and Eosin (H&amp;E), Nissl and Haggqvist staining. The neurons and neuroglia were studied in 25 representative areas, measuring 75166 μm2 in each age group, using the upright binocular optical microscope and image analysis software. The number of neurons and neuroglia with their ratio was calculated and results were statistically analysed using Microsoft Excel software (2010 version). Results: Three types of neurons were identified as multipolar, fusiform and pear-shaped neurons. The ratio of neuroglia to neurons in the three age groups was calculated as: Group A-9.197, Group B-9.274 and Group C-10.478. A p-value of 0.04 was observed on comparing the neuronal and neuroglial density in Group A and C, demonstrating a significant increase in the density of neuroglia with age. Conclusion: The results obtained in the present study can provide prerequisite knowledge to anatomists, pathologists, and neurosurgeons for detection of various pathologies and interventional procedures, respectively.

Author response: Optimal deep brain stimulation site and target connectivity for chronic cluster headache.

We thank Dr. Gupta for his interest in our article.1 Dr. Gupta suggests that a trial of high-dose indomethacin should be considered for patients with chronic cluster headache (CCH). Whether patients with a phenotype of cluster headache (CH), who respond to indomethacin, should be classified as having paroxysmal hemicrania (PH) or indomethacin-responsive CH is unclear. Furthermore, these sparse case reports of indomethacin-responsive CH may be due to a placebo response.2 Headache disorders with the clinical phenotype of either PH or CH that respond to indomethacin should be classified as PH for now, until the pathophysiology of these disorders is better understood.

Reader response: Optimal deep brain stimulation site and target connectivity for chronic cluster headache.

I read with interest the article by Akram et al.1 The investigators accepted that the pathophysiology of cluster headache (CH) is not fully understood, that evidence for primary involvement of the hypothalamus is suggestive, and that primary activation of trigeminoparasympathetic brainstem reflex is uncertain. An unresolved discrepancy exists between posterior hypothalamus and the ventral tegmental area as the key pathophysiologic focus.1–3 The investigators also accepted that the mode of action of deep brain stimulation (DBS), the optimal stimulation site, and the neural networks involved remain poorly understood.1 CH is not a pan-trigeminal disorder, but dominantly involves the ophthalmic division. It is unclear whether DBS selectively affected the ophthalmic trigeminal nerve in this study or how intrinsic trigeminohypothalamic activation can generate unilateral CH.

Editors' note: Optimal deep brain stimulation site and target connectivity for chronic cluster headache

In reference to “Optimal deep brain stimulation site and target connectivity for chronic cluster headache,” Dr. Gupta suggests that patients should fail a trial of indomethacin, at appropriate dose and over an adequate time period, before surgical intervention is considered for cluster headache. Authors Akram et al. contend that patients presenting with the cluster headache phenotype, and who respond to indomethacin, should be classified as having paroxysmal hemicranias based on the International Classification of Headache Disorders, 3rd edition. The authors further clarify that, in their study, patients either failed a trial of indomethacin or that indomethacin was contraindicated. In reference to “Optimal deep brain stimulation site and target connectivity for chronic cluster headache,” Dr. Gupta suggests that patients should fail a trial of indomethacin, at appropriate dose and over an adequate time period, before surgical intervention is considered for cluster headache. Authors Akram et al. contend that patients presenting with the cluster headache phenotype, and who respond to indomethacin, should be classified as having paroxysmal hemicranias based on the International Classification of Headache Disorders, 3rd edition.

Optimal deep brain stimulation site and target connectivity for chronic cluster headache.

Objective:To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area.Methods:Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of ≥30% in headache load.Results:There was no surgical morbidity. Average follow-up was 34 ± 14 months. Patients showed reductions of 76 ± 33% in headache load, 46 ± 41% in attack severity, 58 ± 41% in headache frequency, and 51 ± 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas.Conclusions:We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.

Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity.

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS.

Deep brain stimulation in the globus pallidus externa promotes sleep

The basal ganglia, a network of subcortical structures, play a critical role in movements, sleep and mental behavior. Basal ganglia disorders such as Parkinson’s disease and Huntington’s disease affect sleep. Deep brain stimulation (DBS) to treat motor symptoms in Parkinson’s disease can ameliorate sleep disturbances. Our series of previous studies lead the hypothesis that dopamine, acting on D2 receptors on the striatopallidal terminals, enhances activity in the globus pallidus externa (GPe) and promotes sleep. Here, we tested if DBS in the GPe promotes sleep in rats. We found that unilateral DBS (180Hz at 100μA) in the GPe in rats significantly increased both non-rapid eye movement and rapid eye movement sleep compared to sham DBS stimulation. The EEG power spectrum of sleep induced by DBS was similar to that of the baseline sleep, and sleep latency was not affected by DBS. The GPe is potentially a better site for DBS to treat both insomnia and motor disorders caused by basal ganglia dysfunction.

Functional anatomy of subthalamic nucleus stimulation in Parkinson disease.

We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS. Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site. Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory). Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN.

Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus in idiopathic Parkinson’s disease: Effects on gait initiation and performance

The pedunculopontine tegmental nucleus (PPTg) is a component of the locomotor mesencephalic area. In recent years it has been considered a new surgical site for deep brain stimulation (DBS) in movement disorders. Here, using objective kinematic and spatio-temporal gait analysis, we report the impact of low frequency (40Hz) unilateral PPTg DBS in ten patients suffering from idiopathic Parkinson’s disease with drug-resistant gait and axial disabilities. Patients were studied for gait initiation (GI) and steady-state level walking (LW) under residual drug therapy. In the LW study, a straight walking task was employed. Patients were compared with healthy age-matched controls. The analysis revealed that GI, cadence, stride length and left pelvic tilt range of motion (ROM) improved under stimulation. The duration of the S1 and S2 sub-phases of the anticipatory postural adjustment phase of GI was not affected by stimulation, however a significant improvement was observed in the S1 sub-phase in both the backward shift of centre of pressure and peak velocity. Speed during the swing phase, step width, stance duration, right pelvic tilt ROM phase, right and left hip flexion-extension ROM, and right and left knee ROM were not modified.Overall, the results show that unilateral PPTg DBS may affect GI and specific spatio-temporal and kinematic parameters during unconstrained walking on a straight trajectory, thus providing further support to the importance of the PPTg in the modulation of gait in neurodegenerative disorders.

Reply: The cuneiform nucleus may be involved in the regulation of skeletal muscle tone by motor pathway: a virally mediated trans-synaptic tracing study in surgically sympathectomized mice

Sir, We appreciate the opportunity to respond to the comment by Xiang et al. (2013) on our review on interspecies differences in the pedunculopontine nucleus area. As exemplified by the data of Xiang et al. (2013) it is evident that the mesencephalic locomotor region compromises several distinct structures that are involved in initiation and inhibition of gait, and certainly the implications of both the cuneiform nucleus and the subcuneiform nucleus need to be studied in more detail. Also, as mentioned in our review, there is a paucity of data on the downstream mechanisms mediating neuronal activity in the mesencephalic locomotor region. The role of the pedunculopontine nucleus area as a target site for deep brain stimulation for treatment of medically refractory gait and postural abnormalities in late stage Parkinson’s disease and progressive supranuclear palsy still needs further clarification. Because post-mortem studies in Parkinson’s disease and progressive supranuclear palsy show ∼60% loss of cholinergic neurons in the pedunculopontine nucleus (Jellinger, 1988) it should also …

Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease

Difficulty with step initiation, called "start hesitation," is related to gait bradykinesia and is an early hallmark of gait freezing in Parkinson disease (PD). Authors of this study investigated the effects of deep brain stimulation (DBS) and levodopa on step initiation before and 6 months after DBS surgery in 29 patients with PD who were randomized to either the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) as the DBS site. The authors measured the amplitude and duration of anticipatory postural adjustments (APAs), the feed-forward postural preparation that precedes the onset of voluntary step initiation, based on center-of-pressure displacements on a force plate. They also measured the length and velocity of the first step using a motion analysis system to study kinematics. Some of the patients (22) were from a large, multicenter, double-blind clinical trial, and all patients in the study (29, PD-DBS group) were randomized to DBS in either the bilateral STN (15 patients) or bilateral GPi (14 patients). Differences in step initiation were investigated in 2 conditions before surgery (off/on levodopa) and in 4 conditions after surgery (off/on levodopa combined with off/on DBS). Twenty-eight elderly healthy control volunteers (CTRL group) were also tested, and 9 control volunteers with PD who met the criteria for DBS (PD-C group) were tested at baseline and 6 months later. Patients in the PD-DBS group had smaller amplitudes and longer durations of APAs compared with those in the 28 healthy control volunteers in all conditions. Before surgery, APAs improved with levodopa. After surgery, the APAs were significantly worse than in the best-treatment state before surgery (DOPA condition), and responsiveness to levodopa decreased. No differences in APAs were detected between the STN and GPi groups. A comparison with PD control volunteers who did not undergo DBS surgery confirmed that a deterioration in step preparation was not related to disease progression. Step length and velocity were smaller in the PD-DBS group than in controls in all conditions. Before surgery, levodopa improved the length and velocity of the first step. Both step length and velocity were unchanged in the best-treatment state before surgery (DOPA condition) as compared with after surgery (DBS+DOPA), with only step velocity in the STN group getting worse after surgery. Six months of DBS in the STN or GPi impaired anticipatory postural preparation for step initiation, the opposite effect as with levodopa. Deep brain stimulation disrupted postural preparation more than step execution, suggesting independent motor pathways for preparation and execution of gait. Although turning the stimulators on after surgery combined with levodopa benefited the postural preparation to step, a comparison of pre- and postsurgery conditions suggests that either the surgery itself or 6 months of continuous stimulation may lead to an alteration of circuits or plastic changes that impair step initiation.

Spatiotemporal visualization of deep brain stimulation‐induced effects in the subthalamic nucleus

Deep brain stimulation (DBS) is a successful surgical therapy used to treat the disabling symptoms of movement disorders such as Parkinson's disease. It involves the chronic stimulation of disorder-specific nuclei. However, the mechanisms that lead to clinical improvements remain unclear. Consequently, this slows the optimization of present-day DBS therapy and hinders its future development and application. We used a computational model to calculate the distribution of electric potential induced by DBS and study the effect of stimulation on the spiking activity of a subthalamic nucleus (STN) projection neuron. We previously showed that such a model can reveal detailed spatial effects of stimulation in the vicinity of the electrode. However, this multi-compartmental STN neuron model can fire in either a burst or tonic mode and, in this study, we hypothesized that the firing mode of the cell will have a major impact on the DBS-induced effects. Our simulations showed that the bursting model exhibits behaviour observed in studies of high-frequency stimulation of STN neurons, such as the presence of a silent period at stimulation offset and frequency-dependent stimulation effects. We validated the model by simulating the clinical parameter settings used for a Parkinsonian patient and showed, in a patient-specific anatomical model, that the region of affected tissue is consistent with clinical observations of the optimal DBS site. Our results demonstrated a method of quantitatively assessing neuronal changes induced by DBS, to maximize therapeutic benefit and minimize unwanted side effects.

Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced parkinson's disease

BackgroundDespite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Patients and methodsInvestigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. ResultsThe comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. ConclusionDeep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects.

Long-term benefit from deep brain stimulation of the subthalamic nucleus: is it for everyone?

Although deep brain stimulation (DBS) has revolutionized our approach to therapy for patients with advanced Parkinson's disease, many questions remain. Should DBS be instituted earlier in the course of the disease? Why do some patients show striking improvements whereas others show limited benefit even when lead locations appear to be similar? Why can some patients markedly reduce medications whereas others cannot? What is the optimal target site for DBS and how does it work? One question that has long been asked but only recently become addressable is how long the therapeutic effect of DBS can be sustained in the face of what is still a progressive, neurodegenerative disease? A recent article by Castrioto and colleagues, 'Ten-year outcome of subthalamic stimulation in Parkinson disease', seeks to address this question. The authors report significant improvement at 10 years following the onset of subthalamic nucleus DBS in the off UPDRS (Unified Parkinson's Disease Rating Scale) III total motor score, tremor and bradykinesia subscores, UPDRS II meds on and off scores, and UPDRS IV dyskinesia and motor fluctuation score as well as a significant reduction in the levodopa equivalent daily dose when compared with baseline. Does this finally answer our question of the longevity of DBS? I would suggest not. The article by Castrioto and colleagues provides evidence that some patients can expect improvement for 10 years or longer. However, the young age of onset for patients in this study (average of less than 40 years) combined with a substantial loss of patients to follow-up (23 out of 41) likely leads to a data set that was biased in favor of better long-term outcomes, making it unlikely that the data from this study can be applied to the majority of older patients undergoing DBS, who are more likely to follow a more progressive course. Thus, the present findings are encouraging for some but are not likely to be predictive for all or even for most of the patients currently undergoing this procedure. In spite of these problems, one cannot help but be encouraged by the results of a study that was done early in the course of implementing DBS and that shows continued improvement for patients as long as 10 years following implantation.

Effect of globus pallidus internus stimulation on neuronal activity in the pedunculopontine tegmental nucleus in the primate model of Parkinson's disease

The pedunculopontine tegmental nucleus (PPN) is being explored as a site for deep brain stimulation (DBS) for the treatment of patients with medically refractory gait and postural abnormalities (MRGPA) associated with Parkinson's disease (PD). The PPN is involved in initiation and modulation of gait and other stereotyped motor behaviors and is inter-connected with the pallido-thalamo-cortical circuit. Internal segment of the globus pallidus (GPi) DBS is effective at treating the motor signs associated with PD, however its impact on MRGPA is limited and its effect on PPN neuronal activity is unknown. The current work characterizes the effect of therapeutically-effective GPi DBS on PPN neuronal activity in a single rhesus monkey made parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A scaled-down, quadripolar DBS lead was implanted into sensorimotor GPi under electrophysiological and stereotactic guidance. Single-neuron activity was recorded from PPN before, during and after DBS. GPi DBS reduced the mean discharge rate of PPN neurons from 16.8Hz to 12.8Hz, with 30 (66.7%) neurons showing a decreased mean rate, 3 (6.7%) increased and 12 (26.7%) unchanged. Consistent with known GABAergic projections from GPi to PPN, and with previous observations that stimulation increases output from the stimulated structure, GPi DBS suppressed activity in the PPN. The present observations, together with previous reports of improvement in MRGPA during low frequency stimulation in PPN, suggest that activation of PPN output may be required to improve MRGPA and may account for the lack of improvement in MRGPA typically observed with GPi or subthalamic nucleus (STN) DBS.

The trajectory of apathy after deep brain stimulation: From pre-surgery to 6 months post-surgery in Parkinson’s disease

Deep brain stimulation (DBS) has been associated with increased apathy in patients with PD, yet studies lack longitudinal data and have not assessed differences between sites of implantation (i.e. STN versus GPi). We assessed apathy prior to surgery and 6 months post-surgery using a longitudinal design–latent growth curve modeling. We hypothesized that apathy would increase post-surgery, and be related to subthalamic nucleus (versus globus pallidus interna) implantation. Forty-eight PD patients underwent unilateral surgery to either GPi or STN and completed the Apathy Scale prior to surgery and 2, 4, and 6 months post-surgery. Forty-eight matched PD controls completed the Apathy Scale at a 6-month interval. Results indicated apathy increased linearly from pre- to 6-months post-DBS by .66 points bi-monthly, while apathy in the control group did not change. There was no relationship between apathy and DBS site. Higher baseline depression was associated with higher baseline apathy, but not with change in apathy. Middle-aged adults (<65) had a steeper trajectory of apathy than older adults (≥65). Apathy trajectory was not related to motor severity, laterality of DBS, levodopa medication reduction, or motor changes after surgery.

A Magnetic Resonance Imaging–Directed Method for Transventricular Targeting of Midline Structures for Deep Brain Stimulation Using Implantable Guide Tubes

The periventricular gray/periaqueductal gray (PVG/PAG) is a target site for deep brain stimulation for chronic pain. The pedunculopontine nucleus (PPN) is a target for the treatment of axial disturbance in Parkinson's disease. Conventionally, a trajectory lateral to the ventricle is used in targeting deep subcortical structures; however, this limits the number of active contacts that can be placed in these midline targets. To maximize the number of contacts within these targets, a trajectory traversing the ventricles may be used; however, this is avoided because lead placement remains unpredictable with problems including ventricular lead migration and hemorrhage. We describe a novel method for accurate and safe transventricular targeting. Magnetic resonance imaging is used for visualizing the target structure. A trajectory traversing the lateral ventricle is planned, avoiding blood vessels. The guide tube is inserted through the ventricle to a position short of the target site and its proximal end is fixed. A stylet is inserted in the guide tube with its distal end at the target site. After intraoperative radiological confirmation of placement, the indwelling stylet is removed and the guide tube acts as a port for delivering the stimulating electrode. The PVG/PAG matter and the PPN were targeted, taking a transventricular trajectory. We implanted unilateral PVG/PAG matter electrodes in 10 patients and bilateral PPN electrodes in 3 patients. All electrodes were implanted accurately within the desired target with no complications. The use of an implanted guide tube enables the safe and accurate transventricular targeting of the PVG/PAG matter and the PPN.

Is the target for thalamic deep brain stimulation the same as for thalamotomy?

Deep brain stimulation (DBS) has virtually replaced thalamotomy for the treatment of essential tremor. It is thought that the site for DBS is the same as the optimal lesion site; however, this match has not been investigated previously. We sought to determine whether the location of thalamic DBS matched the site at which thalamotomy would be performed. Eleven patients who had detailed microelectrode recording and stimulation for placement of DBS electrodes and subsequent successful tremor control were analysed. An experienced surgeon, blinded to outcome and final electrode position, selected the ideal thalamotomy site based on the reconstructed maps obtained intraoperatively. When the site of long-term clinically used DBS and theoretical thalamotomy location was calculated in three-dimensional space and compared for each of the x, y, and z axes in stereotactic space, there was no significant difference in the mediolateral location of DBS and theoretical lesion site. There was also no difference between the theoretical lesion site and the placement of the tip of the electrode; however, the active electrodes used for chronic stimulation were significantly more anterior (P = 0.005) and dorsal (P = 0.034) to the ideal thalamotomy target. This mismatch may reflect the compromise required between adverse and beneficial effects with chronic stimulation, but it also suggests different mechanisms of effect of DBS and thalamotomy.