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OBJECTIVE Suboptimal lead placement is one of the most common indications for deep brain stimulation (DBS) revision procedures. Confirming lead placement in relation to the visible anatomical target with dedicated stereotactic imaging before terminating the procedure can mitigate this risk. In this study, the authors examined the accuracy, precision, and safety of intraoperative MRI (iMRI) to both guide and verify lead placement during frame-based stereotactic surgery. METHODS A retrospective analysis of 650 consecutive DBS procedures for targeting accuracy, precision, and perioperative complications was performed. Frame-based lead placement took place in an operating room equipped with an MRI machine using stereotactic images to verify lead placement before removing the stereotactic frame. Immediate lead relocation was performed when necessary. Systematic analysis of the targeting error was calculated. RESULTS Verification of 1201 DBS leads with stereotactic MRI was performed in 643 procedures and with stereotactic CT in 7. The mean ± SD of the final targeting error was 0.9 ± 0.3 mm (range 0.1–2.3 mm). Anatomically acceptable lead placement was achieved with a single brain pass for 97% (n = 1164) of leads; immediate intraoperative relocation was performed in 37 leads (3%) to obtain satisfactory anatomical placement. General anesthesia was used in 91% (n = 593) of the procedures. Hemorrhage was noted after 4 procedures (0.6%); 3 patients (0.4% of procedures) presented with transient neurological symptoms, and 1 experienced delayed cognitive decline. Two bleeds coincided with immediate relocation (2 of 37 leads, 5.4%), which contrasts with hemorrhage in 2 (0.2%) of 1164 leads implanted on the first pass (p = 0.0058). Three patients had transient seizures in the postoperative period. The seizures coincided with hemorrhage in 2 of these patients and with immediate lead relocation in the other. There were 21 infections (3.2% of procedures, 1.5% in 3 months) leading to hardware removal. Delayed (> 3 months) retargeting of 6 leads (0.5%) in 4 patients (0.6% of procedures) was performed because of suboptimal stimulation benefit. There were no MRI-related complications, no permanent motor deficits, and no deaths. CONCLUSIONS To the authors’ knowledge, this is the largest series reporting the use of iMRI to guide and verify lead location during DBS surgery. It demonstrates a high level of accuracy, precision, and safety. Significantly higher hemorrhage was encountered when multiple brain passes were required for lead implantation, although none led to permanent deficit. Meticulous audit and calibration can improve precision and maximize safety.

ObjectiveTo present long term outcomes of ventral tegmental area (VTA) deep brain stimulation (DBS) for medically refractory chronic cluster headache (CCH) and short-lasting unilateral neuralgiform headache attacks (SUNHA)MethodsOpen label study using prospectively collected clinical data in consecutive patients treated by VTA DBS between 2009 and 2019 in a single tertiary neuroscience centre, treated by a multidisciplinary team.ResultsBetween 2009 and 2019, 71 patients (43 CCH and 28 SUNHA) were treated with VTA DBS. Mean duration of follow up was 5.6 years (range 1.0-11.7 years).Overall, there was a significant improvement in attack frequency, attack severity, and attack duration in both groups (all pAdverse events were rareFour non-responders had the DBS system explanted, two of them secondary to infection and one due to post-surgical neuropathic pain around the head wound site. Four patients died from unrelated conditions during the study period.ConclusionsThis study provides open label evidence than VTA DBS is a safe and effective treatment for refractory CCH and SUNHA, an effect which is maintained at long term follow up.

Background: Degeneration of the nucleus basalis of Meynert (NBM) and cortical cholinergic dysfunction are hallmarks of Parkinson's disease dementia (PDD). There is no effective therapy for PDD. Deep brain stimulation of the NBM (NBM-DBS) has been trialed as a potential treatment. Objective: Our primary aim was to evaluate the sustained tolerability of NBM-DBS in PDD, and its impact on global cognition, behavioral symptoms, quality of life and caregiver burden and distress. Second, we aimed to determine whether baseline measures of arousal, alertness, and attention were predictive of the three year response to NBM-DBS in PDD patients. Methods: Five of the six PDD patients who completed the baseline assessment participated in a 3 year follow up assessment. We assessed the participants after three years of NBM-DBS on the Mini Mental State Examination, Dementia Rating Scale-2, Blessed Dementia Rating Scale, Neuropsychiatric Inventory, and the SF36. Results: The five patients showed varying trajectories of cognitive decline, with two showing a slower progression over the three-year follow-up period. A slower progression of decline on global cognition was associated with higher baseline accuracy on the Posner covert orienting of attention test, and less daytime sleepiness. Conclusions: Whether slower progression of cognitive decline in two patients was in any way related to individual variability in responsiveness to NBM-DBS requires confirmation in a larger series including an unoperated PDD control group. Higher accuracy in covertly orienting attention and better sleep quality at baseline were associated with better cognitive outcomes at 36 months assessment. These results require validation in future studies with larger samples.

Patients with Parkinson’s disease can develop axial symptoms, including speech, gait and balance difficulties. Chronic high-frequency (>100 Hz) deep brain stimulation can contribute to these impairments while low-frequency stimulation (, Vijiaratnam et al. report beneficial and durable improvements in axial complications of subthalamic nucleus deep brain stimulation with low frequency stimulation in one of the largest cohorts reported to date. Less severe tremor and an earlier occurrence of axial complications during post-operative follow-up predicts the durability of low frequency stimulation, which is a novel finding., Graphical Abstract Graphical Abstract

Beta oscillations are readily observed in motor cortex and the basal ganglia, but to which extent they are functionally relevant is unclear. To understand how activity transfer between different nodes of the cortico-basal ganglia network is affected by cortical beta oscillations in different behavioural conditions, we recorded local field potentials and electroencephalography (EEG) activity in a low-force motor control task and during rest in Parkinson's patients undergoing deep brain stimulation (DBS) surgery. The patients received DBS of either the subthalamic nucleus (STN) or the internal globus pallidus (GPi), which allowed us to investigate if STN and GPi broad-band high-frequency activity (HFA; >150 Hz) is co-modulated with the phase of motor cortical beta activity. We found significant modulation patterns in the STN and the GPi, which were inverted while patients performed the task, showing that GPi activity fluctuations likely are crafted by other inputs than the direct excitatory STN afferents. We also found that consistent STN modulation disappeared during rest, showing disengagement in this condition, while GPi modulation was maintained, again evidencing that beta-band activity fluctuations in the GPi can be relatively independent of those in the STN. The difference between HFA modulation patterns in the task and rest recordings suggests a potential functional role of beta phase-locked HFA modulation in controlling sustained contractions. Examination of HFA co-modulation patterns at different sites of the cortico-basal ganglia-thalamo-cortical network under different behavioural conditions may provide a tool with which to define the impact of beta synchronization on network communication.

Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping., Patients with advanced Parkinson's can be treated by deep brain stimulation (DBS) of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of 10 Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of DBS strategies to ameliorate gait impairments. SIGNIFICANCE STATEMENT We tested whether the subthalamic nucleus (STN) in humans is causally involved in controlling stepping movements. To this end, we studied patients with Parkinson's disease who have undergone therapeutic deep brain stimulation (DBS), as in these individuals we can stimulate the STNs in a controlled manner. We developed an alternating pattern of stimulation that mimics the pattern of activity modulation recorded in this nucleus during stepping. The alternating DBS (altDBS) could entrain patients' stepping rhythm, suggesting a causal role of the STN in dynamic gait control. This type of stimulation may potentially form the basis for improved DBS strategies for gait.

Background: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. Objectives: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. Materials and Methods: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson’s disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20–30 Hz and optimized in an iterative manner. Results: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. Conclusions: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson’s disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60μs, but there is limited data available on the effect of shorter PWs. Objective: To define the TW of STN-DBS in PD at PW of 30μs (PW30) relative to standard PW settings at 60μs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. Methods: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. Results: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. Conclusions: STN-DBS in PD patients using a PW of 30μs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30μs settings.

Gait disturbances in Parkinson's disease are commonly refractory to current treatment options and majorly impair patient's quality of life. Auditory cues facilitate gait and prevent motor blocks. We investigated how neural dynamics in the human subthalamic nucleus of Parkinsons's disease patients (14 male, 2 female) vary during stepping and whether rhythmic auditory cues enhance the observed modulation. Oscillations in the beta band were suppressed after ipsilateral heel strikes, when the contralateral foot had to be raised, and reappeared after contralateral heel strikes, when the contralateral foot rested on the floor. The timing of this 20–30 Hz beta modulation was clearly distinct between the left and right subthalamic nucleus, and was alternating within each stepping cycle. This modulation was similar, whether stepping movements were made while sitting, standing, or during gait, confirming the utility of the stepping in place paradigm. During stepping in place, beta modulation increased with auditory cues that assisted patients in timing their steps more regularly. Our results suggest a link between the degree of power modulation within high beta frequency bands and stepping performance. These findings raise the possibility that alternating deep brain stimulation patterns may be superior to constant stimulation for improving parkinsonian gait.SIGNIFICANCE STATEMENTGait disturbances in Parkinson's disease majorly reduce patients' quality of life and are often refractory to current treatment options. We investigated how neural activity in the subthalamic nucleus of patients who received deep brain stimulation surgery covaries with the stepping cycle. 20–30 Hz beta activity was modulated relative to each step, alternating between the left and right STN. The stepping performance of patients improved when auditory cues were provided, which went along with enhanced beta modulation. This raises the possibility that alternating stimulation patterns may also enhance beta modulation and may be more beneficial for gait control than continuous stimulation, which needs to be tested in future studies.

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.

INTRODUCTION: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS.METHODS: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test).RESULTS: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test.CONCLUSIONS: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.

Background Dementia with Lewy bodies (DLB) is the second most common form of dementia. Current symptomatic treatment with medications remains inadequate. Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a potential new treatment option in dementias. Objective To assess the safety and tolerability of low frequency (20 Hz) NBM DBS in DLB patients and explore its potential effects on both clinical symptoms and functional connectivity in underlying cognitive networks. Methods We conducted an exploratory randomised, double-blind, crossover trial of NBM DBS in six DLB patients recruited from two UK neuroscience centres. Patients were aged between 50 and 80 years, had mild-moderate dementia symptoms and were living with a carer-informant. Patients underwent image guided stereotactic implantation of bilateral DBS electrodes with the deepest contacts positioned in the Ch4i subsector of NBM. Patients were subsequently assigned to receive either active or sham stimulation for six weeks, followed by a two week washout period, then the opposite condition for six weeks. Safety and tolerability of both the surgery and stimulation were systematically evaluated throughout. Exploratory outcomes included the difference in scores on standardised measurements of cognitive, psychiatric and motor symptoms between the active and sham stimulation conditions, as well as differences in functional connectivity in discrete cognitive networks on resting state fMRI. Results Surgery and stimulation were well tolerated by all six patients (five male, mean age 71.33 years). One serious adverse event occurred: one patient developed antibiotic-associated colitis, prolonging his hospital stay by two weeks. No consistent improvements were observed in exploratory clinical outcome measures, but the severity of neuropsychiatric symptoms reduced with NBM DBS in 3/5 patients. Active stimulation was associated with functional connectivity changes in both the default mode network and the frontoparietal network. Conclusion Low frequency NBM DBS can be safely conducted in DLB patients. This should encourage further exploration of the possible effects of stimulation on neuropsychiatric symptoms and corresponding changes in functional connectivity in cognitive networks. Trial registration number NCT02263937.

Objective Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Approach Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. Main results This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. Significance The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.

BACKGROUND: Magnetic resonance imaging (MRI)-verified deep brain stimulation relies on the correct interpretation of stereotactic imaging documenting lead location in relation to visible anatomic target. However, it has been suggested that local signal distortion from the lead itself renders its depiction on MRI unreliable. OBJECTIVE: To compare lead location on stereotactic MRI with subsequent location of its brain track after removal. METHODS: Patients underwent deep brain stimulation with the use of MRI-guided and MRI-verified Leksell frame approach. Infection or suboptimal efficacy required lead removal and subsequent reimplantation by using the same technique. Postimplantation stereotactic MR images were analyzed. Lateral (x) and anteroposterior (y) distances from midcommissural point to center of the lead hypointensity were recorded at the anterior commissure-posterior commissure plane (pallidal electrode) or z = 24 (subthalamic electrode). Stereotactic MRI before the second procedure, x and y distances from the center of the visible lead track hypointensity to midcommissural point were independently recorded. Vectorial distance from center of the lead hypointensity to the center of its track was calculated. RESULTS: Sixteen electrode tracks were studied in 10 patients. Mean differences between lead artifact location and lead track location were: x coordinate 0.4 mm +/- 0.2; y coordinate 0.6 mm +/- 0.3. Mean vectorial distance was 0.7 mm +/- 0.2. CONCLUSION: Stereotactic distance between lead location and subsequent brain track location on MRI was small. The mean discrepancy was approximately half the deep brain stimulation lead width. This suggests that lead hypointensity seen on postimplantation MRI is indeed an accurate representation of its real location within deep brain structures.

Summary Background Deep brain stimulation (DBS) has been proposed as a treatment option for severe Tourette's syndrome on the basis of findings from open-label series and small double-blind trials. We aimed to further assess the safety and efficacy of bilateral globus pallidus internus (GPi) DBS in patient's with severe Tourette's syndrome. Methods In a randomised, double-blind, crossover trial, we recruited eligible patients (severe medically refractory Tourette's syndrome, age ≥20 years) from two clinics for tertiary movement disorders in the UK. Enrolled patients received surgery for GPi DBS and then were randomly assigned in a 1:1 ratio (computer-generated pairwise randomisation according to order of enrolment) to receive either stimulation on-first or stimulation off-first for 3 months, followed by a switch to the opposite condition for a further 3 month period. Patients and rating clinicians were masked to treatment allocation; an unmasked clinician was responsible for programming the stimulation. The primary endpoint was difference in Yale Global Tic Severity Scale (YGTSS) total score between the two blinded conditions, assessed with repeated measures ANOVA, in all patients who completed assessments during both blinded periods. After the end of the blinded crossover phase, all patients were offered continued DBS and continued to have open-label stimulation adjustments and objective assessments of tic severity until database lock 1 month after the final patient's final trial-related visit. This trial is registered with ClinicalTrials.gov, number NCT01647269. Findings Between Nov 5, 2009, and Oct 16, 2013, we enrolled 15 patients (11 men, four women; mean age 34·7 years [SD 10·0]). 14 patients were randomly assigned and 13 completed assessments in both blinded periods (seven in the on-first group, six in the off-first group). Mean YGTSS total score in these 13 patients was 87·9 (SD 9·2) at baseline, 80·7 (SD 12·0) for the off-stimulation period, and 68·3 (SD 18·6) for the on-stimulation period. Pairwise comparisons in YGTSS total scores after Bonferroni correction were significantly lower at the end of the on-stimulation period compared with the off-stimulation period, with a mean improvement of 12·4 points (95% CI 0·1–24·7, p=0·048), equivalent to a difference of 15·3% (95% CI 5·3–25·3). All 15 patients received stimulation in the open-label phase. Overall, three serious adverse events occurred (two infections in DBS hardware at 2 and 7 weeks postoperatively, and one episode of deep-brain-stimulation-induced hypomania during the blinded on-stimulation period); all three resolved with treatment. Interpretation GPi stimulation led to a significant improvement in tic severity, with an overall acceptable safety profile. Future research should concentrate on identifying the most effective target for DBS to control both tics and associated comorbidities, and further clarify factors that predict individual patient response. Funding UK National Health Service.

OBJECT Bibliometrics are the methods used to quantitatively analyze scientific literature. In this study, bibliometrics were used to quantify the scientific output of neurosurgical departments throughout Great Britain and Ireland. METHODS A list of neurosurgical departments was obtained from the Society of British Neurological Surgeons website. Individual departments were contacted for an up-to-date list of consultant (attending) neurosurgeons practicing in these departments. Scopus was used to determine the h-index and m-quotient for each neurosurgeon. Indices were measured by surgeon and by departmental mean and total. Additional information was collected about the surgeon's sex, title, listed superspecialties, higher research degrees, and year of medical qualification. RESULTS Data were analyzed for 315 neurosurgeons (25 female). The median h-index and m-quotient were 6.00 and 0.41, respectively. These were significantly higher for professors (h-index 21.50; m-quotient 0.71) and for those with an additional MD or PhD (11.0; 0.57). There was no significant difference in h-index, m-quotient, or higher research degrees between the sexes. However, none of the 16 British neurosurgery professors were female. Neurosurgeons who specialized in functional/epilepsy surgery ranked highest in terms of publication productivity. The 5 top-scoring departments were those in Addenbrooke's Hospital, Cambridge; St. George's Hospital, London; Great Ormond Street Hospital, London; National Hospital for Neurology and Neurosurgery, Queen Square, London; and John Radcliffe Hospital, Oxford. CONCLUSIONS The h-index is a useful bibliometric marker, particularly when comparing between studies and individuals. The m-quotient reduces bias toward established researchers. British academic neurosurgeons face considerable challenges, and women remain underrepresented in both clinical and academic neurosurgery in Britain and Ireland.

Background Both the cerebral cortex and subcortical structures play important roles in consciousness. Some evidence points to general anaesthesia-induced unconsciousness being associated with distinct patterns of superficial cortical electrophysiological oscillations, but how general anaesthetics influence deep brain neural oscillations and interactions between oscillations in humans is poorly understood. Methods Local field potentials were recorded in discrete deep brain regions, including anterior cingulate cortex, sensory thalamus, and periaqueductal grey, in humans with implanted deep brain electrodes during induction of unconsciousness with propofol. Power-frequency spectra, phase-amplitude coupling, coherence, and directed functional connectivity analysis were used to characterise local field potentials in the awake and unconscious states. Results An increase in alpha (7–13 Hz) power and decrease in gamma (30–90 Hz) power were observed in both deep cortical (ACC, anterior cingulate cortex) and subcortical (sensory thalamus, periaqueductal grey) areas during propofol-induced unconsciousness. Robust alpha-low gamma (30–60 Hz) phase-amplitude coupling induced by general anaesthesia was observed in the anterior cingulate cortex but not in other regions studied. Moreover, alpha oscillations during unconsciousness were highly coherent within the anterior cingulate cortex, and this rhythm exhibited a bidirectional information flow between left and right anterior cingulate cortex but stronger left-to-right flow. Conclusion Propofol increases alpha oscillations and attenuates gamma oscillations in both cortical and subcortical areas. The alpha-gamma phase-amplitude coupling and the functional connectivity of alpha oscillations in the anterior cingulate cortex could be specific markers for loss of consciousness.

BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.

Gamma activity in the subthalamic nucleus (STN) is widely viewed as a pro-kinetic rhythm. Here we test the hypothesis that rather than being specifically linked to movement execution, gamma activity reflects dynamic processing in this nucleus. We investigated the role of gamma during fast stopping and recorded scalp electroencephalogram and local field potentials from deep brain stimulation electrodes in 9 Parkinson’s disease patients. Patients interrupted finger tapping (paced by a metronome) in response to a stop-signal sound, which was timed such that successful stopping would occur only in ~50% of all trials. STN gamma (60–90 Hz) increased most strongly when the tap was successfully stopped, whereas phase-based connectivity between the contralateral STN and motor cortex decreased. Beta or theta power seemed less directly related to stopping. In summary, STN gamma activity may support flexible motor control as it did not only increase during movement execution but also during rapid action-stopping. DOI: http://dx.doi.org/10.7554/eLife.23947.001, eLife digest Being able to stop walking to allow a car to pass is one example of how terminating a movement midway through can be essential for surviving in an ever-changing world. However, people with Parkinson’s disease sometimes struggle to stop performing a repetitive movement. Also, they may find themselves stopping despite having intended to keep moving. This inability to control stopping and starting can play havoc with everyday activities such as walking. Some people with Parkinson’s disease find that their symptoms improve after a treatment called deep brain stimulation. Surgeons lower electrodes into specific regions of the brain and use them to block the abnormal electrical activity that causes problems with movement. One of the main brain regions targeted is an area called the subthalamic nucleus. Whenever people initiate a movement, nerve cells in the subthalamic nucleus start to become activated at the same time. This synchronization generates rhythmic waves of activity in the subthalamic nucleus, which are called gamma waves. To find out whether gamma waves are also involved in stopping a movement, Fischer et al. measured activity in the subthalamic nucleus of nine patients with Parkinson’s disease as they performed a finger tapping exercise. The patients had to tap their finger in time with a metronome, but refrain from tapping whenever they heard a high pitched noise. As expected, a burst of gamma waves accompanied the start of each finger tap. However, Fischer et al. showed that an increase in gamma waves also occurred whenever patients successfully stopped a finger tap midway. Gamma waves may thus help people to interact flexibly with the world around them. Techniques like deep brain stimulation have the potential to manipulate gamma waves. In order to treat symptoms without causing side effects, we need to work out how to target brain waves that are altered in patients, without disrupting other processes. A key step towards achieving this is to understand how brain waves change during essential behaviours such as stopping an on-going movement. DOI: http://dx.doi.org/10.7554/eLife.23947.002

The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback. In dystonic subjects, we found that auditory feedback was associated with the presence of high gamma oscillations nestled on a negative deflection, morphologically similar to sharp wave ripple complexes described in human rhinal cortex. These were not present in Parkinson's disease subjects. The temporal properties of the high gamma burst were modified by incorrect trial performance compared to correct trial performance. Both groups exhibited a robust low frequency response to 'incorrect' trial performance in dominant GPi but not non-dominant GPi at theta frequency. Our results suggest that cellular processes associated with striatum-dependent memory function may be selectively impaired in Parkinson's disease even if dopaminergic drugs are administered, but that error detection mechanisms are preserved.

Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract.To assess the relevance of pyramidal tract activation with STN-DBS in PD.In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography.Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility.Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society.

Motor imagery involves cortical networks similar to those activated by real movements, but the extent to which the basal ganglia are recruited is not yet clear. Gamma and beta oscillations in the subthalamic nucleus (STN) vary with the effort of sustained muscle activity. We recorded local field potentials in Parkinson's disease patients and investigated if similar changes can be observed during imagined gripping at three different ‘forces’. We found that beta activity decreased significantly only for imagined grips at the two stronger force levels. Additionally, gamma power significantly scaled with increasing imagined force. Thus, in combination, these two spectral features can provide information about the intended force of an imaginary grip even in the absence of sensory feedback. Modulations in the two frequency bands during imaginary movement may explain the rehabilitating benefit of motor imagery to improve motor performance. The results also suggest that STN LFPs may provide useful information for brain-machine interfaces., Highlights • We tested to which extent the subthalamic nucleus is involved in motor imagery. • During real gripping at three force levels beta and gamma activity is scaled. • Force-dependent modulation also was observed during imagined gripping. • STN neuro-feedback may support motor training or brain-machine interfaces.

Background Traumatic brain injury (TBI) is a worldwide health concern associated with significant morbidity and mortality. In the United States, severe TBI is managed according to recommendations set forth in 2007 by the Brain Trauma Foundation (BTF), which were based on relatively low quality clinical trials. These guidelines prescribed the use of hypothermia for the management of TBI. Several randomized controlled trials (RCTs) of hypothermia for TBI have since been conducted. Despite this new literature, there is ongoing controversy surrounding the use of hypothermia for the management of severe TBI. Methods We searched the PubMed database for all RCTs of hypothermia for TBI since 2007 with the intent to review the methodology outcomes of these trials. Furthermore, we aimed to develop evidence-based, expert opinions based on these recent studies. Results We identified 8 RCTs of therapeutic hypothermia published since 2007 that focused on changes in neurologic outcomes or mortality in patients with severe TBI. The majority of these trials did not identify improvement with the use of hypothermia, though there were subgroups of patients that may have benefited from hypothermia. Differences in methodology prevented direct comparison between studies. Conclusions A growing body of literature disfavors the use of hypothermia for the management of severe TBI. In general, empiric hypothermia for severe TBI should be avoided. However, based on the results of recent trials, there may be some patients, such as those in Asian centers or with focal neurologic injury, who may benefit from hypothermia.

Dr. Henry Hans Heinz Schmidek (b. 10th September 1937) died suddenly in Oxford on 26th October 2008 after myocardial infarction. British neurosurgery and Oxford will be the poorer because he had pl...

Emotion and reward have been proposed to be closely linked to conscious experience, but empirical data are lacking. The anterior cingulate cortex (ACC) plays a central role in the hedonic dimension of conscious experience; thus potentially a key region in interactions between emotion and consciousness. Here we tested the impact of emotion on conscious experience, and directly investigated the role of the ACC. We used a masked paradigm that measures conscious reportability in terms of subjective confidence and objective accuracy in identifying the briefly presented stimulus in a forced-choice test. By manipulating the emotional valence (positive, neutral, negative) and the presentation time (16 ms, 32 ms, 80 ms) we measured the impact of these variables on conscious and subliminal (i.e. below threshold) processing. First, we tested normal participants using face and word stimuli. Results showed that participants were more confident and accurate when consciously seeing happy versus sad/neutral faces and words. When stimuli were presented subliminally, we found no effect of emotion. To investigate the neural basis of this impact of emotion, we recorded local field potentials (LFPs) directly in the ACC in a chronic pain patient. Behavioural findings were replicated: the patient was more confident and accurate when (consciously) seeing happy versus sad faces, while no effect was seen in subliminal trials. Mirroring behavioural findings, we found significant differences in the LFPs after around 500 ms (lasting 30 ms) in conscious trials between happy and sad faces, while no effect was found in subliminal trials. We thus demonstrate a striking impact of emotion on conscious experience, with positive emotional stimuli enhancing conscious reportability. In line with previous studies, the data indicate a key role of the ACC, but goes beyond earlier work by providing the first direct evidence of interaction between emotion and conscious experience in the human ACC.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.

Neurosurgery can alter cardiorespiratory performance via central networks and includes deep brain stimulation (DBS), a routinely employed therapy for movement disorders and chronic pain syndromes. We review the established cardiovascular effects of DBS and the presumed mechanism by which they are produced via the central autonomic network. We then review the respiratory effects of DBS, including modulation of respiratory rate and lung function indices, and the mechanisms via which these may occur. We conclude by highlighting the potential future therapeutic applications of DBS for intractable airway diseases.

Documentation of urgent referrals to neurosurgical units and communication with referring hospitals is critical for effective handover and appropriate continuity of care within a tertiary service. Referrals to our neurosurgical unit were audited and we found that the majority of referrals were not documented and this led to more calls to the on-call neurosurgery registrar regarding old referrals. We implemented a new referral system in an attempt to improve documentation of referrals, communication with our referring hospitals and to professionalise the service we offer them.During a 14-day period, number of bleeps, missed bleeps, calls discussing new referrals and previously processed referrals were recorded. Whether new referrals were appropriately documented and referrers received a written response was also recorded. A commercially provided secure cloud-based data archiving telecommunications and database platform for referrals was subsequently introduced within the Trust and the questionnaire repeated during another 14-day period 1 year after implementation.Missed bleeps per day reduced from 16% (SD ± 6.4%) to 9% (SD ± 4.8%; df = 13, paired t-tests p = 0.007) and mean calls per day clarifying previous referrals reduced from 10 (SD ± 4) to 5 (SD ± 3.5; df = 13, p = 0.003). Documentation of new referrals increased from 43% (74/174) to 85% (181/210), and responses to referrals increased from 74% to 98%.The use of a secure cloud-based data archiving telecommunications and database platform significantly increased the documentation of new referrals. This led to fewer missed bleeps and fewer calls about old referrals for the on call registrar. This system of documenting referrals results in improved continuity of care for neurosurgical patients, a significant reduction in risk for Trusts and a more efficient use of Registrar time.

Objectives: Pallidal stimulation and pallidotomy are known to improve the symptoms of Parkinson's disease (PD). However, it is not known which modality produces greater benefit in patients who have already undergone unilateral pallidotomy. It is also suggested that the original pallidal surgery provides a greater benefit than subsequent pallidal surgery. The aim of this study was to analyze which modality produced greater PD symptom improvement in patients with a prior pallidotomy and whether the chronological order of the pallidal surgery influenced the size of the improvement. Methods: Five patients who had undergone a prior unilateral pallidotomy for PD were studied. Because of ongoing Parkinsonian symptoms, all patients subsequently underwent contralateral pallidal surgery, either a further pallidotomy or pallidal stimulation. All surgeries were performed by a single functional neurosurgeon and the patients prospectively assessed and scored at routine follow-ups. Paired-sample t-tests were used to detect differences in outcomes after first and second surgeries. Results: Two patients underwent pallidal stimulation and three underwent a second pallidotomy. Mean follow-up was 13.5 months and 12.3 months, respectively. Greater percentage improvements in the majority of scores were found after pallidal stimulation compared with a second pallidotomy, namely Unified Parkinson's Disease Rating Scale (UPDRS) II off (25.22% vs. −3.27%), UPDRS III off (36.15% vs. 5.21%), rigidity (58.34% vs. 11.54%), tremor (5.56% vs. −30.48%), bradykinesia (48.55% vs. −2.23%), gait composite (16.52% vs. −51.79%), dyskinesia duration (83.33% vs. 66.67%), dyskinesia disability (100% vs. 66.67%), speech (10% vs. −50%), and the proportion of the day spent in the “off” state (50% vs. 25%). Comparing outcomes after the first surgery to those after the second surgery, statistical differences were found in dyskinesia duration improvement and ipsilateral dyskinesia improvement after the second surgery (p

Importance Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia. Objective To evaluate the safety and potential symptomatic effects of NBM DBS in patients with Parkinson disease dementia. Design, Setting, and Participants A randomized, double-blind, crossover clinical trial evaluated the results of 6 patients with Parkinson disease dementia who were treated with NBM DBS at a neurosurgical referral center in the United Kingdom from October 26, 2012, to July 31, 2015. Eligible patients met the diagnostic criteria for Parkinson disease dementia, had motor fluctuations, were appropriate surgical candidates aside from the coexistence of dementia, were age 35 to 80 years, were able to give informed consent, had a Mini-Mental State Examination score of 21 to 26, had minimal atrophy seen on results of brain magnetic resonance imaging, and lived at home with a caregiver-informant. Interventions After surgery, patients were assigned to receive either active stimulation (bilateral, low-frequency [20 Hz] NBM DBS) or sham stimulation for 6 weeks, followed by the opposite condition for 6 weeks. Main Outcomes and Measures The primary outcome was the difference in scores on each item of an abbreviated cognitive battery (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale-III digit span, verbal fluency, Posner covert attention test, and simple and choice reaction times) between the 2 conditions. Secondary outcomes were exploratory and included differences in scores on standardized measurements of cognitive, psychiatric, and motor symptoms and resting state functional magnetic resonance imaging. Results Surgery and stimulation were well tolerated by all 6 patients (all men; mean [SD] age, 65.2 [10.7] years), with no serious adverse events during the trial. No consistent improvements were observed in the primary cognitive outcomes or in results of resting state functional magnetic resonance imaging. An improvement in scores on the Neuropsychiatric Inventory was observed with NBM DBS (8.5 points [range, 4-26 points]) compared with sham stimulation (12 points [range, 8-38 points]; median difference, 5 points; 95% CI, 2.5-8.5 points; P = .03) and the preoperative baseline (13 points [range, 5-25 points]; median difference, 2 points; 95% CI, −8 to 5.5 points; P = .69). Conclusions and Relevance Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms. Trial Registration clinicaltrials.gov Identifier:NCT01701544

Objective: To present outcomes in a cohort of medically intractable chronic cluster headache (CCH) patients treated with ventral tegmental area (VTA) deep brain stimulation (DBS). Methods: In an uncontrolled open-label prospective study, 21 patients (17 male; mean age 52 years) with medically refractory CCH were selected for ipsilateral VTA-DBS by a specialist multidisciplinary team including a headache neurologist and functional neurosurgeon. Patients had also failed or were denied access to occipital nerve stimulation within the UK National Health Service. The primary endpoint was improvement in the headache frequency. Secondary outcomes included other headache scores (severity, duration, headache load), medication use, disability and affective scores, quality of life (QoL) measures, and adverse events. Results: Median follow-up was 18 months (range 4–60 months). At the final follow-up point, there was 60% improvement in headache frequency ( p = 0.007) and 30% improvement in headache severity ( p = 0.001). The headache load (a composite score encompassing frequency, severity, and duration of attacks) improved by 68% ( p = 0.002). Total monthly triptan intake of the group dropped by 57% posttreatment. Significant improvement was observed in a number of QoL, disability, and mood scales. Side effects included diplopia, which resolved in 2 patients following stimulation adjustment, and persisted in 1 patient with a history of ipsilateral trochlear nerve palsy. There were no other serious adverse events. Conclusions: This study supports that VTA-DBS may be a safe and effective therapy for refractory CCH patients who failed conventional treatments. Classification of evidence: This study provides Class IV evidence that VTA-DBS decreases headache frequency, severity, and headache load in patients with medically intractable chronic cluster headaches.

Parkinsons disease (PD) is a neurodegenerative disorder caused in part by the loss of dopaminergic neurones in the substantia nigra (pars compacta). This results in disruption of the normal oscillatory and synchronous neuronal activity between the cortex, globus pallidus interna (GPi) and subthalamic nuleus (STN), The three cardinal clinical manifestations of PD are bradykinesia, tremor and rigidity. Gait and postural instability is often also seen. This chapter explores the place of surgery in the management of PD. It was once the mainstay of treatment, in the form of ablative surgeries such as pedunculotomy, and was then made largely redundant by the advent of dopaminergic drugs. However, it was found that dopaminergic drugs caused side effects including dyskinesias, which could be severely incapacitating. Once again, surgery (commonly taking the form of deep brain stimulation) became an important modality in the management of PD, not only to treat the cardinal symptoms of the disease itself, but also to treat the dyskinetic side effects of medical therapy.

Introduction. Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. Materials and methods. Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. Results. I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = − 13.218, p < 0·0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0·001), 20% had 11 correct perceptions (p = 0·013). III) S/N: > 80% tremor reduction occurred in 99/114 ‘On’ trials (87%), and 3/114 ‘Off’ trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. Conclusions. DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. Classification of evidence. This study is the first to provide Class I evidence for the efficacy of DBS for ET.

Infant vocalizations are among the most biologically salient sounds in the environment and can draw the listener to the infant rapidly in both times of distress and joy. A region of the midbrain, the periaqueductal gray (PAG), has long been implicated in the control of urgent, survival-related behaviours. To test for PAG involvement in the processing of infant vocalizations, we recorded local field potentials from macroelectrodes implanted in this region in four adults who had undergone deep brain stimulation. We found a significant difference occurring as early as 49 ms after hearing a sound in activity recorded from the PAG in response to infant vocalizations compared with constructed control sounds and adult and animal affective vocalizations. This difference was not present in recordings from thalamic electrodes implanted in three of the patients. Time frequency analyses revealed distinct patterns of activity in the PAG for infant vocalisations, constructed control sounds and adult and animal vocalisations. These results suggest that human infant vocalizations can be discriminated from other emotional or acoustically similar sounds early in the auditory pathway. We propose that this specific, rapid activity in response to infant vocalizations may reflect the initiation of a state of heightened alertness necessary to instigate protective caregiving.

Deep brain stimulation (DBS) is an expanding field in neurosurgery and has already provided important insights into the fundamental mechanisms underlying brain function. One of the most exciting emerging applications of DBS is modulation of blood pressure, respiration and micturition through its effects on the autonomic nervous system. DBS stimulation at various sites in the central autonomic network produces rapid changes in the functioning of specific organs and physiological systems that are distinct from its therapeutic effects on central nervous motor and sensory systems. For example, DBS modulates several parameters of cardiovascular function, including heart rate, blood pressure, heart rate variability, baroreceptor sensitivity and blood pressure variability. The beneficial effects of DBS also extend to improvements in lung function. This article includes an overview of the anatomy of the central autonomic network, which consists of autonomic nervous system components in the cortex, diencephalon and brainstem that project to the spinal cord or cranial nerves. The effects of DBS on physiological functioning (particularly of the cardiovascular and respiratory systems) are discussed, and the potential for these findings to be translated into therapies for patients with autonomic diseases is examined. © 2012 Macmillan Publishers Limited.