The Modern Utility of Awake Deep Brain Stimulation Surgery

The Modern Utility of Awake Deep Brain Stimulation Surgery | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search The Modern Utility of Awake Deep Brain Stimulation Surgery Bryan T. Klassen , Matthew R. Baker , Kai J. Miller doi: https://doi.org/10.1101/2025.09.25.25336654 Bryan T. Klassen 1 Department of Neurology , Mayo Clinic, Rochester, MN, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: Klassen.Bryan{at}mayo.edu Matthew R. Baker 2 Department of Neurosurgery , Mayo Clinic, Rochester, MN, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kai J. Miller 2 Department of Neurosurgery , Mayo Clinic, Rochester, MN, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background Awake deep brain stimulation (DBS) surgery with microelectrode recording (MER) and test stimulation offers real-time physiologic feedback to refine lead placement, but its relevance is increasingly debated in an era of advanced imaging and streamlined asleep workflows. Objective To describe a contemporary framework for awake DBS with MER and to evaluate whether, in our hands, this approach results in a final lead position different from what we would have achieved with asleep DBS. Methods We outline a standardized workflow combining high-resolution imaging, confirmatory MER, and intraoperative stimulation mapping for an example context of thalamic targeting for essential tremor. To quantify the impact of the awake approach on surgical decision making, we retrospectively reviewed the first 137 consecutively implanted VIM DBS leads placed (awake) by a single surgeon working with a single intraoperative neurologist. In each case, we recorded whether the final lead was implanted along the planned target, whether it was adjusted in depth along the planned trajectory, or whether it was moved to a parallel track. For the parallel track moves, we compared the final lead position to the initially planned imaging target using co-registered pre- and postoperative imaging. Results Among 137 consecutive leads implanted, 116 were implanted in the planned trajectory, with 49 at the planned depth and 67 at an adjusted depth. Twenty-one of the 137 leads were placed along a parallel trajectory based on intraoperative findings, with seventeen having available imaging for further analysis. Post-operative analysis showed that only 2 of the 17 were moved toward the intended target. The remaining 15 were moved away (13) or equidistant (2) from the intended target. Conclusion Feedback from MER and test stimulation in awake DBS cases frequently informs surgical adjustments that deviate from the planned trajectory, often in response to patient-specific physiology not captured by imaging. In the vast majority of our cases, these adjustments would not have been made using an asleep DBS approach, since moves were not made toward the planned target. This indicates that, in our practice, awake surgery results in adjustment of lead position in response to discovered functional anatomy rather than to correct stereotactic inaccuracy. Our findings underscore the continued utility in our practice of awake DBS with MER in tailoring therapy to individual anatomy and functional organization. Introduction At its inception, deep brain stimulation (DBS) for the treatment of movement disorders was reliant upon detailed atlases of inferred anatomic boundaries that could be understood when compared with anatomic landmarks identified on intraoperative ventriculography. 1 , 2 Intraoperative teams of neurosurgeons, neurologists and neurophysiologists would conduct sophisticated multitrack studies of baseline cell firing patterns, changes in cell activity (firing rate) during sensory/motor tasks, and behavioral responses to test stimulation to infer the correct position for permanent deep brain stimulation electrode placement. 3 – 5 Generations of patients have benefited as a result. In the past 35 years, there have been dramatic breakthroughs in brain imaging, in the accuracy of stereotactic targeting, and in the understanding of the brain’s responses to stimulation. The ability to fuse images of many different types with each other and the ability to obtain volumetric imaging before, during, and after DBS electrode placement have allowed for precise electrode delivery to intended anatomic structures 6 – 8 Although some of these structures are easily visible on MRI, the boundaries between and within other structures remain elusive, and they are typically delineated on the basis of standard atlases registered to the patient’s MRI. With this ability to target anatomic structures with high fidelity, coupled with the ability to confirm the position of DBS leads in the operating room, the ongoing utility of awake DBS is reasonably questioned. Although most patients are able to tolerate the awake DBS procedure, it can be psychologically distressing and logistically difficult. 9 , 10 A clinical team’s insistence on awake DBS may result in some patients deciding to forgo an otherwise life-changing therapy. In our own practice, we perform both awake and asleep DBS on a weekly basis. We perform lead placement under general anesthesia in cases where awake interoperate behavioral testing is unlikely to predict efficacy or side effects (for example DBS for epilepsy), or in cases of patients clearly unable or unwilling to tolerate awake DBS. However, we have continued to perform almost all of our DBS implants for adults with movement disorders in the awake state with microelectrode recording and test stimulation. In our practice, we predominantly begin with exploration of 1-2 tracks, and our testing is focused on confirming expected electrophysiology and behavioral responses based upon MRI-presumed anatomic locations. The purpose of this manuscript is to assess the utility in continuing to perform movement disorders cases awake, by assessing the five year interval since the beginning of the surgeon’s practice (KJM) working with the same intraoperative neurologist (BTK), using Vim nucleus of the thalamus targeting for essential tremor as the illustrative test context. We then discuss our general DBS practice and how we attempt to maximize clinical outcomes by synthesizing classical approaches with the modern tools now at our disposal. Methods In order to evaluate the utility of awake DBS surgery, we retrospectively reviewed five years of a single surgeon’s practice, beginning with their first case in independent practice after training and ending in late 2024. Vim DBS cases were assessed as the test case in order to constrain analyses to a single indication and anatomic target. The procedure was performed with approximately the same protocol over this interval, although improved MRI sequences and improved Atlas segmentation were integrated as they became available. All of our patients received a Boston Scientific rechargeable system with segmented leads having a 1-3-3-1 pattern (levels that are 1.5mm long, with 0.5 mm between contact levels). The methodology described is not proposed to be superior to that of others who might use different approaches for targeting or intraoperative lead confirmation, but is provided for context. The purpose of our present analyses is to assess to what degree the awake component of the surgery may have influenced decision-making and placement of DBS leads that might differ from a purely asleep approach by the same surgeon. Ethics statement The study was conducted according to the Institutional Review Board of the Mayo Clinic (IRB 19-009878). Each patient provided informed written consent as approved by the IRB. Surgical Planning Preoperative selection of the Vim thalamic target was performed using the Stealth or BrainLab navigation software environments, and was informed by 1) indirect AC-PC targeting (on the AC-PC axis at a point posterior to mid-commisural point by 25% of the AC-PC distance and ∼10 mm lateral to the wall of the 3rd ventricle), 2) standard MNI-space atlases normalized to patient space, 3) diffusion tractography delineating the dentatorubrothalamic tract (DRTT), medial lemniscus, and internal capsule, and in many patients 4) direction visualization of DRTT fibers and the internal capsule on white-matter nulled MRI sequences ( Fig. 1A ; 7 , 11 – 13 ). Download figure Open in new tab Fig 1. Awake deep brain stimulation (DBS) surgical workflow. (A) Preoperative planning integrates indirect targeting (ACPC coordinates), deformed atlases, and structural and diffusion imaging (FGATIR, tractography) to define surgical targets and trajectories. (B) Microelectrode recordings (MER) involves inserting high-impedance electrodes into target structures to record single-cell activity and local field potentials. (C) Macrostimulation testing uses the ring electrode to assess therapeutic efficacy and side effect thresholds to confirm or reposition the lead. (D) In suboptimal cases, additional tracks can be tested. These moves may be closer to the target, correcting for stereotactic error, or farther/equidistant moves that would typically not be made by imaging alone. Stereotactic Implantation Leksell G-frames were used for each surgery, and these were serviced on a regular basis. The Leksell frame base was placed using local anesthesia in the preoperative area, and a mixed-phase contrast thin-cut zero-gantry volumetric CT was used for registration. This was registered to preoperative MRIs and the predetermined targets using the navigation software. Nearly all patients underwent bilateral implantation. Microelectrode Recording Microelectrode recording was performed using the Alpha Omega Neuromega system. For cases in which multimodal planning data fully converged on a clear target, the initial recording was made along a single trajectory using the center BenGun channel. In cases with some divergence between modalities, recordings were made along multiple simultaneous trajectories, with the center channel aligned with what we thought was most likely the optimal target. A microelectrode is passed into the cannula, and advanced in submillimeter increments towards the target ( Fig. 1B ). Patterns of background change single unit activity and tuning to behavior are assessed at each depth in order to: Identify borders between structures. Identify characteristic patterns found in different structures. Identify functional correlates of movement or sensory inputs. Identify correlates of disease (the most common of these is tremor cells; Fig. 2 ). Download figure Open in new tab Fig 2. Features of microelectrode recordings (MER) used for optimal deep brain stimulation (DBS) lead placement. MER identifies white to gray matter transitions based on single-unit firing and background (e.g. quiet white matter into highly active subthalamic nucleus). Characteristic firing patterns can also be distinguished between regions, such as bursting or pausing cells in the external globus pallidus (GPe), and border and irregular firing cells in the internal globus pallidus (GPi). Neurons in the ventral intermediate nucleus of the thalamus (VIM) may be tuned to passive movement (kinesthetic cells) or pathologic tremor as seen on electromyography (EMG). As the “ring electrode” nears target, test stimulation is performed. Test Stimulation Initial test stimulation was applied through the ring contact on the microelectrode cannula, typically in a position 2 mm above the target depth. If the results of the observed microelectrode and test stimulation were consistent with those expected from the plan, the permanently implantable DBS lead was placed at target. Next, bipolar stimulation was the applied using the Boston Scientific external neurostimulator using a frequency of 130 Hz, pulse width of 60 microseconds, and step-wise increase in amplitude up to 3-4 mA. Patients were evaluated for tremor improvement and stimulation-induced side effects ( Fig. 1C ). If the intraoperative neurologist thought there was not a sufficient therapeutic window between tremor resolution and side effect, an additional pass was made along a parallel trajectory 2 mm away, while keeping the original cannula in place to minimize displacement of brain tissue. Retrospective Analysis of Final Lead Placement To evaluate how awake monitoring influences final lead placement in our DBS surgeries, we retrospectively analyzed 137 leads consecutively implanted in the course of awake thalamic (Vim) DBS for essential tremor. All analyses of lead location was performed independent of the neurosurgeon and neurologist (by MRB). Surgical records were reviewed to determine whether the final lead was implanted in the center track (at the planned or at an adjusted depth) or moved to a parallel (off-center) track. For cases requiring off-center adjustments, we coregistered the preoperative imaging to the postoperative head CT and compared the preoperative plan with the final lead location (as marked by the lead artifact). The position of the originally implanted track was calculated by offset to the lead artifact and used to determine whether the off-center adjustment served to move the lead closer to (suggesting correction of stereotactic error) or further from (suggesting a purposeful deviation based on patient-specific physiology) the planned target ( Fig. 1D ). Results Of the 137 Vim DBS leads implanted for essential tremor, 49 (36%) leads were implanted in the center track without any adjustment. Sixty-seven leads (49%) were implanted along the center track but to an adjusted depth, while 21 patients (15%) were implanted in a non-central trajectory based on feedback from awake testing. Among the 21 off-center cases, 17 had suitable preoperative and postoperative imaging for retrospective analysis. As shown in Table 1 , the distances of lead artifact from the planned target varied, with adjustments ranging from 1.0 mm to 3.2 mm. In 13 of these 17 leads (76%) adjustments moved the lead further away from the planned target, indicating a deliberate deviation based on physiologic findings rather than correction of targeting error. In 2 cases (12%) the lead was moved an equal distance across the planned target, an adjustment that would not have been made on the basis of imaging alone. Only 2 leads (12%) were moved closer to the imaging-defined target ( Table 2 ). View this table: View inline View popup Download powerpoint Table 1. Final lead placement and physiologic deviation in VIM deep brain stimulation (DBS) cases. Deviations in final DBS lead placement relative to the imaging-defined center track. These deviations may reflect results from microelectrode recording (MER), macrostimulation testing, or both. “Toward” indicates movement closer to the preoperative target; “Away” indicates deviation based on physiologic data; “Same” indicates a move across the planned target resulting in the same distance. View this table: View inline View popup Download powerpoint Table 2. Definitions of microelectrode recording (MER) strategies in DBS surgery. Discussion Awake DBS with MER remains a practical and valuable approach in the era of advanced imaging. While modern asleep workflows leverage high-resolution MRI, tractography, and intraoperative volumetric imaging for targeting, 4 , 7 these tools do not eliminate the unique information gained from real-time physiologic feedback. In our practice, awake confirmatory MER has been incorporated into a streamlined workflow that adds only 10–15 minutes per side, ensuring efficiency without compromising thoroughness. Importantly, the use of an awake protocol should not be conflated with cutting corners elsewhere: all patients still undergo the full battery of preoperative imaging, and we maintain rigorous intraoperative imaging standards, using O-arm volumetric imaging before closure in asleep cases, and fluoroscopy with immediate postoperative CT in awake cases. This combined approach underscores that awake testing is not a legacy technique competing with modern imaging, but a complementary method that refines placement based on patient-specific physiology in ways that imaging alone cannot. Value of Real-Time Clinical and Physiologic Feedback A central advantage of awake surgery is the ability to directly observe therapeutic effects and side effects during stimulation, providing the most immediate and reliable estimate of clinical efficacy. This intraoperative feedback loop allows the surgical team to weigh benefit against adverse effects in real time, something that is not possible when relying solely on imaging endpoints. 14 While microlesional effects from lead insertion can transiently improve symptoms and potentially obscure the therapeutic window, stimulation can still reveal negative side effects, offering a more robust signal of suboptimal placement. 15 When awake, repositioning decisions are thus driven by clinical considerations, whereas in asleep workflows such judgments are made based on the inferred effects of stimulation at an imaging-defined anatomic site. In our series, only 2 of the 17 off-center adjustments would have been made in response to intraoperative imaging findings. Thus, in our hands just over 10 percent of all leads would have been sub-optimially positioned if we had used an asleep workflow. Depth optimization is a critical but often underappreciated element of lead placement. Most modern DBS leads have radially-segmented electrodes spanning only 3.5mm, meaning that even small shifts in depth will determine whether eccentric tuning of the stimulation field is possible near the physiologic “sweet spot.”. 16 , 17 In our series, more than half of the leads would not have been positioned to maximize this range without MER-guided depth adjustments. While imaging can confirm that a trajectory passes through the intended target nucleus, it cannot verify that the highest-yield physiologic zone is centered within the limited span of the lead’s contact array. Awake MER provides the opportunity to make this fine adjustment in real time, helping to align the functional core of the target with the most programmable portion of the lead. While most patients experience meaningful benefit from Deep brain stimulation regardless of surgical approach, 9 , 18 , 19 our experience suggests that awake monitoring with MER meaningfully reduces the risk of suboptimal placement. Based on intraoperative judgment, approximately one in eight leads would have been left in a suboptimal position had we relied solely on imaging guidance. By allowing us to refine placement intraoperatively, awake MER shifts a subset of leads from merely “good enough” to “ideal”. This advantage carries downstream implications: when the lead is optimally positioned, programming is more straightforward and efficient for the neurology team up front. Ideal anatomic lead placement will also ensure that stimulation of greater volumes of tissue around the electrodes is tolerated in the future, at which point disease progression may require the use of more aggressive stimulating parameters. Intraoperative physiologic recordings may also hold increasing value as closed-loop DBS technologies emerge, 20 – 22 offering a way to identify patient-specific biomarkers or verify that a known biomarker is present at the implant site, ensuring that the chosen location will support future adaptive stimulation strategies. MER paradigms In our workflow, MER is approached as a structured yet flexible tool that adapts to the surgical context and the patient’s anatomy. We distinguish between three conceptual paradigms: exploratory, confirmatory, and performative ( table 2 ). Exploratory MER involves the routine use of multiple simultaneous tracks to build a three-dimensional physiological map of the target region and was commonly used prior to the era of modern imaging; this may still be a reasonable approach when entering unfamiliar anatomy or in complex revision cases. However, this guarantees multiple brain penetrations and typically is quite time consuming. Our general approach is Confirmatory MER with a 1-2 electrodes advanced along the planned trajectory to verify that expected physiologic signatures are present at the appropriate depths; additional tracks are deployed if findings suggest misalignment or ambiguous localization. By contrast, performative MER (recording for billing purposes, without intent to influence surgical decision-making) carries the burdens of awake surgery without offering actionable feedback and is inappropriate. Framing MER through these paradigms helps clarify that its value lies not in its mere use, but in its purposeful integration into surgical decision-making. Why might an “optimal” imaging outcome not produce optimal therapy? Even with meticulous planning and high-resolution imaging, the functionally optimal site for Deep brain stimulation (DBS) may not align precisely with the planned anatomical coordinates. Several factors may contribute to this mismatch. First, there is natural variability in the spatial representation of somatotopy and tracts within nuclei. 23 , 24 Second, neuronal elements associated with stimulation-induced therapeutic effects may interdigitate with those associated with side-effect, in which case side effects may emerge even at seemingly ideal anatomic targets. 25 Third, structural variation across individuals, particularly at borders like the Vop–Vim transition, is not reliably visible on any current imaging. 26 Finally, the brain itself deforms in response to the advancing rigid cannula, and the surrounding tissue strains and displaces around it, so even a perfectly aligned trajectory can deviate subtly from the intended anatomy, and this may or may not be appreciated on intraoperative imaging. These realities underscore why MER-guided “deviations” are not errors, but deliberate refinements based on functional data that imaging cannot provide. When awake DBS may not be appropriate The benefits of awake Deep brain stimulation (DBS) with microelectrode recording (MER) are substantial, but only when patients can actively engage in the intraoperative process. Excessive anxiety, including claustrophobia, can make the experience intolerable and undermine cooperation during testing. Cognitive impairment can similarly limit a patient’s ability to respond reliably to commands, confounding clinical and physiologic mapping. Certain physical conditions also pose risk: severe axial dystonia, tics, or fixed painful postures can increase the chance of frame slippage or injury if attempted awake. Moreover, some indications inherently do not offer immediate behavioral feedback and lie far from structures that produce acute side effects, such as targeting the anterior nucleus of the thalamus (ANT) for epilepsy, and therefore cannot benefit from awake testing. In such cases, asleep implantation leveraging intraoperative volumetric imaging is preferable. However, even in these cases MER can still provide useful information regarding structural borders. Conclusion Awake DBS surgery with microelectrode recording remains a relevant and valuable approach in the era of advanced imaging. While not possible for every patient or every case, MER provides actionable information that can alter surgical decisions, refine lead positioning, and personalize therapy. As we continue to explore new paradigms in neuromodulation, preserving and refining physiologic guidance may be essential not only to improve current outcomes, but to enable the next generation of precision DBS. Download figure Open in new tab Fig S1. Direction and magnitude of physiologically-guided lead adjustments relative to planned target and initial center track. Schematic plots for each of the 17 leads demonstrate the planned target (red circle), the initial center track (blue ring), and the final lead position after a move (yellow star). Arrows indicate the direction of the 2mm move in the BenGun. only 2/17 leads were moved towards the intended target, while the remaining were either farther away (13) or equidistant (2). Data Availability All data produced in the present work are contained in the manuscript. Acknowledgments This work was supported by the National Institutes of Health (NIH) NINDS U01-NS128612 (MRB, KJM). Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. MRB, KJM, and BTK were supported by the MN partnership grant for biotechnology and medical genomics (MNP2142). MRB and KJM were also supported by a Helene Houle Career Development Award and the Tianqiao & Chrissy Chen Institute. 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