The Interictal Suppression Hypothesis in focal epilepsy: network-level supporting evidence.

Why are people with focal epilepsy not continuously having seizures? Previous neuronal signalling work has implicated gamma-aminobutyric acid balance as integral to seizure generation and termination, but is a high-level distributed brain network involved in suppressing seizures? Recent intracranial electrographic evidence has suggested that seizure-onset zones have increased inward connectivity that could be associated with interictal suppression of seizure activity. Accordingly, we hypothesize that seizure-onset zones are actively suppressed by the rest of the brain network during interictal states. Full testing of this hypothesis would require collaboration across multiple domains of neuroscience. We focused on partially testing this hypothesis at the electrographic network level within 81 individuals with drug-resistant focal epilepsy undergoing presurgical evaluation. We used intracranial electrographic resting-state and neurostimulation recordings to evaluate the network connectivity of seizure onset, early propagation and non-involved zones. We then used diffusion imaging to acquire estimates of white-matter connectivity to evaluate structure-function coupling effects on connectivity findings. Finally, we generated a resting-state classification model to assist clinicians in detecting seizure-onset and propagation zones without the need for multiple ictal recordings. Our findings indicate that seizure onset and early propagation zones demonstrate markedly increased inwards connectivity and decreased outwards connectivity using both resting-state (one-way ANOVA, P-value = 3.13 × 10-13) and neurostimulation analyses to evaluate evoked responses (one-way ANOVA, P-value = 2.5 × 10-3). When controlling for the distance between regions, the difference between inwards and outwards connectivity remained stable up to 80 mm between brain connections (two-way repeated measures ANOVA, group effect P-value of 2.6 × 10-12). Structure-function coupling analyses revealed that seizure-onset zones exhibit abnormally enhanced coupling (hypercoupling) of surrounding regions compared to presumably healthy tissue (two-way repeated measures ANOVA, interaction effect P-value of 9.76 × 10-21). Using these observations, our support vector classification models achieved a maximum held-out testing set accuracy of 92.0 ± 2.2% to classify early propagation and seizure-onset zones. These results suggest that seizure-onset zones are actively segregated and suppressed by a widespread brain network. Furthermore, this electrographically observed functional suppression is disproportionate to any observed structural connectivity alterations of the seizure-onset zones. These findings have implications for the identification of seizure-onset zones using only brief electrographic recordings to reduce patient morbidity and augment the presurgical evaluation of drug-resistant epilepsy. Further testing of the interictal suppression hypothesis can provide insight into potential new resective, ablative and neuromodulation approaches to improve surgical success rates in those suffering from drug-resistant focal epilepsy.

Intraoperative physiology augments atlas-based data in awake deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort. METHODS: Data from 451 patients with movement disorders treated with 822 individual DBS leads at a single institution from 2011 to 2021 were included. Atlas-based data was used to guide surgical targeting. Intraoperative testing data and coordinate data were retrospectively obtained from a large patient database. Medical records were reviewed to obtain active contact usage and neurologist-defined outcomes at 1 year. RESULTS: Microelectrode recording firing profiles differ per track, per target and inform the locations where macrostimulation testing is performed. Macrostimulation performance correlates with the final electrode track chosen. Centroids of atlas-based efficacy heat maps per target were close in proximity to and may predict active contact usage at 1 year. Overall, patient outcomes at 1 year were improved for patients with better macrostimulation response. CONCLUSIONS: Atlas-based imaging data is beneficial for target planning and intraoperative guidance, and in conjunction with intraoperative neurophysiological testing during awake DBS can be used to individualize and optimise final electrode positioning, resulting in favourable outcomes.

Automated Whole Cochlear T2 Signal Demonstrates Weak Correlation with Hearing Loss in Observed Vestibular Schwannoma.

INTRODUCTION: We sought to evaluate the correlation between whole cochlear T2 signal changes obtained with a novel automated segmentation method and hearing levels, both at diagnosis and over time, in patients with observed vestibular schwannoma. METHODS: This retrospective correlation study within an academic medical center neurotology practice evaluated 127 patients with vestibular schwannoma observed over time, each with ≥2 MRI scans (367 total) and ≥2 audiograms (472 total). 86 patients had T2-weighted sequences with sufficient resolution for cochlear signal analysis, yielding 348 unique timepoint intervals. The main outcome measure was correlation of the ipsilateral-to-contralateral ratio of whole cochlear T2 signal with hearing outcomes as measured by pure tone average (PTA) and word recognition score (WRS). RESULTS: Whole cochlear T2 signal ratios did not show a correlation with hearing levels at diagnosis. Change in signal ratio over time showed weak correlation with changes in PTA, but not WRS, over time. Cochlear signal ratio did not precede changes in hearing but did follow changes in both PTA and WRS. CONCLUSION: Whole cochlear T2 signal ratios were weakly correlated with changes in hearing in patients with observed vestibular schwannoma. The technology of automated segmentation and signal processing holds promise for future evaluation of clinical entities causing cochlear signal changes.

Non-Expert Markings of Active Chronic Graft-Versus-Host Disease Photographs: Optimal Metrics of Training Effects.

Lack of reliable measures of cutaneous chronic graft-versus-host disease (cGVHD) remains a significant challenge. Non-expert assistance in marking photographs of active disease could aid the development of automated segmentation algorithms, but validated metrics to evaluate training effects are lacking. We studied absolute and relative error of marked body surface area (BSA), redness, and the Dice index as potential metrics of non-expert improvement. Three non-experts underwent an extensive training program led by a board-certified dermatologist to mark cGVHD in photographs. At the end of the 4-month training, the dermatologist confirmed that each trainee had learned to accurately mark cGVHD. The trainees' inter- and intra-rater intraclass correlation coefficient estimates were "substantial" to "almost perfect" for both BSA and total redness. For fifteen 3D photos of patients with cGVHD, the trainees' median absolute (relative) BSA error compared to expert marking dropped from 20 cm2 (29%) pre-training to 14 cm2 (24%) post-training. Total redness error decreased from 122 a*·cm2 (26%) to 95 a*·cm2 (21%). By contrast, median Dice index did not reflect improvement (0.76 to 0.75). Both absolute and relative BSA and redness errors similarly and stably reflected improvements from this training program, which the Dice index failed to capture.

Intraoperative Correction of Cochlear Implant Electrode Translocation.

INTRODUCTION: Translocation of precurved cochlear implant (CI) electrodes reduces hearing outcomes, but it is not known whether it is possible to correct scalar translocation such that all electrodes reside fully in the scala tympani (ST). METHODS: Six cadaveric temporal bones were scanned with CT and segmented to delineate intracochlear anatomy. Mastoidectomy with facial recess was performed. Precurved CI electrodes (CI532; Cochlear Limited) were implanted until scalar translocation was confirmed with postoperative CT. Then, electrodes were removed and replaced. CT scan was repeated to assess for translocation correction. Scalar position of electrode contacts, angular insertion depth (AID) of the electrode array, and M- (average distance between each electrode contact and the modiolus) were measured. An in vivo case is reported in which intraoperative translocation detection led to removal and replacement of the electrode. RESULTS: Five of 6 cadaveric translocations (83%) were corrected with 1 attempt, resulting in full ST insertions. AID averaged 285 ± 77° for translocated electrodes compared to 344 ± 28° for nontranslocated electrodes (p = 0.109). M- averaged 0.75 ± 0.18 mm for translocated electrodes and 0.45 ± 0.11 mm for nontranslocated electrodes (p = 0.016). Reduction in M- with translocation correction averaged 38%. In the in vivo case, translocation was successfully corrected in a single attempt. CONCLUSION: Scalar translocation of precurved CI electrodes can be corrected by removal and reinsertion. This significantly improves the perimodiolar positioning of these electrodes. There was a high rate of success (83%) in this cadaveric model as well as a successful in vivo attempt.

Speech recognition as a function of the number of channels for Mid-Scala electrode array recipients.

This study investigated the number of channels needed for maximum speech understanding and sound quality in 15 adult cochlear implant (CI) recipients with Advanced Bionics (AB) Mid-Scala electrode arrays completely within scala tympani. In experiment I, CI programs used a continuous interleaved sampling (CIS)-based strategy and 4-16 active electrodes. In experiment II, CI programs used an n-of-m strategy featuring 16 active electrodes with either 8- or 12-maxima. Speech understanding and sound quality measures were assessed. For CIS programs, participants demonstrated performance gains using up to 4-10 electrodes on speech measures and sound quality ratings. For n-of-m programs, there was no significant effect of maxima, suggesting 8-maxima is sufficient for this sample's maximum performance and sound quality. These results are largely consistent with previous studies using straight electrode arrays [e.g., Fishman, Shannon, and Slattery (1997). J. Speech Lang. Hear. Res. 40, 1201-1215; Friesen, Shannon, Baskent, and Wang (2001). J. Acoust. Soc. Am. 110, 1150-1163; Shannon, Cruz, and Galvin (2011). Audiol. Neurotol. 16, 113-123; Berg, Noble, Dawant, Dwyer, Labadie, and Gifford (2020). J. Acoust. Soc. Am. 147, 3646-3656] and in contrast with recent studies looking at cochlear precurved electrode arrays [e.g., Croghan, Duran, and Smith (2017). J. Acoust. Soc. Am. 142, EL537-EL543; Berg, Noble, Dawant, Dwuer, Labadie, and Gifford (2019b). J. Acoust. Soc. Am. 145, 1556-1564], which found continuous improvements up to 16 independent channels. These findings suggest that Mid-Scala electrode array recipients demonstrate similar channel independence to straight electrode arrays rather than other manufacturer's precurved electrode arrays.

Speech recognition as a function of the number of channels for an array with large inter-electrode distances.

This study investigated the number of channels available to cochlear implant (CI) recipients for maximum speech understanding and sound quality for lateral wall electrode arrays-which result in large electrode-to-modiolus distances-featuring the greatest inter-electrode distances (2.1-2.4 mm), the longest active lengths (23.1-26.4 mm), and the fewest number of electrodes commercially available. Participants included ten post-lingually deafened adult CI recipients with MED-EL electrode arrays (FLEX28 and STANDARD) entirely within scala tympani. Electrode placement and scalar location were determined using computerized tomography. The number of channels was varied from 4 to 12 with equal spatial distribution across the array. A continuous interleaved sampling-based strategy was used. Speech recognition, sound quality ratings, and a closed-set vowel recognition task were measured acutely for each electrode condition. Participants did not demonstrate statistically significant differences beyond eight channels at the group level for almost all measures. However, several listeners showed considerable improvements from 8 to 12 channels for speech and sound quality measures. These results suggest that channel interaction caused by the greater electrode-to-modiolus distances of straight electrode arrays could be partially compensated for by a large inter-electrode distance or spacing.

Structural Correlates of the Sensorimotor Cerebellum in Parkinson's Disease and Essential Tremor.

BACKGROUND: Parkinson's disease (PD) and essential tremor (ET) are commonly encountered movement disorders. Pathophysiologic processes that localize to the cerebellum are described in both. There are limited studies investigating cerebellar structural changes in these conditions, largely because of inherent challenges in the efficiency of segmentation. METHODS: We applied a novel multiatlas cerebellar segmentation method to T1-weighted images in 282 PD and 111 essential tremor patients to define 26 cerebellar lobule volumes. The severity of postural and resting tremor in both populations and gait and postural instability in PD patients were defined using subscores of the UPDRS and Washington Heights-Inwood Genetic Study motor scales. These clinical measurements were related to lobule volume size. Multiple comparisons were controlled using a false discovery rate method. RESULTS: Group differences were identified between ET and PD patients, with reductions in deep cerebellar nucleus volume in ET versus reduced lobule VI volume in PD. In ET patients, lobule VIII was negatively correlated with the severity of postural tremor. In PD patients, lobule IV was positively correlated with resting tremor and total tremor severity. We observed differences in cerebellar structure that localized to sensorimotor lobules of the cerebellum. Lobule volumes appeared to differentially relate to clinical symptoms, suggesting important clinicopathologic distinctions between these conditions. These results emphasize the role of the cerebellum in tremor symptoms and should foster future clinical and pathologic investigations of the sensorimotor lobules of the cerebellum. © 2020 International Parkinson and Movement Disorder Society.

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.

Speech recognition with cochlear implants as a function of the number of channels: Effects of electrode placement.

This study investigated the effects of cochlear implant (CI) electrode array type and scalar location on the number of channels available to CI recipients for maximum speech understanding and sound quality. Eighteen post-lingually deafened adult CI recipients participated, including 11 recipients with straight electrode arrays entirely in scala tympani and 7 recipients with translocated precurved electrode arrays. Computerized tomography was used to determine electrode placement and scalar location. In each condition, the number of channels varied from 4 to 22 with equal spatial distribution across the array. Speech recognition (monosyllables, sentences in quiet and in noise), subjective speech sound quality, and closed-set auditory tasks (vowels, consonants, and spectral modulation detection) were measured acutely. Recipients with well-placed straight electrode arrays and translocated precurved electrode arrays performed similarly, demonstrating asymptotic speech recognition scores with 8-10 channels, consistent with the classic literature. This finding contrasts with recent work [Berg, Noble, Dawant, Dwyer, Labadie, and Gifford. (2019). J. Acoust. Soc. Am. 145, 1556-1564] that found precurved electrode arrays well-placed in scala tympani demonstrate continuous performance gains beyond 8-10 channels. Given these results, straight and translocated precurved electrode arrays are theorized to have less channel independence secondary to their placement farther away from neural targets.

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. METHODS: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. RESULTS: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. SIGNIFICANCE: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

Crowdsourcing to delineate skin affected by chronic graft-vs-host disease.

BACKGROUND: Estimating the extent of affected skin is an important unmet clinical need both for research and practical management in many diseases. In particular, cutaneous burden of chronic graft-vs-host disease (cGVHD) is a primary outcome in many trials. Despite advances in artificial intelligence and 3D photography, progress toward reliable automated techniques is hindered by limited expert time to delineate cGVHD patient images. Crowdsourcing may have potential to provide the requisite expert-level data. MATERIALS AND METHODS: Forty-one three-dimensional photographs of three cutaneous cGVHD patients were delineated by a board-certified dermatologist. 410 two-dimensional projections of the raw photos were each annotated by seven crowd workers, whose consensus performance was compared to the expert. RESULTS: The consensus delineation by four of seven crowd workers achieved the highest agreement with the expert, measured by a median Dice index of 0.7551 across all 410 images, outperforming even the best worker from the crowd (Dice index 0.7216). For their internal agreement, crowd workers achieved a median Fleiss's kappa of 0.4140 across the images. The time a worker spent marking an image had only weak correlation with the surface area marked, and very low correlation with accuracy. Percent of pixels selected by the consensus exhibited good correlation (Pearson R = 0.81) with the patient's affected surface area. CONCLUSION: Crowdsourcing may be an efficient method for obtaining demarcations of affected skin, on par with expert performance. Crowdsourced data generally agreed with the current clinical standard of percent body surface area to assess cGVHD severity in the skin.

Speech recognition as a function of the number of channels in perimodiolar electrode recipients.

This study investigated the number of channels needed for maximum speech understanding and sound quality in 30 adult cochlear implant (CI) recipients with perimodiolar electrode arrays verified via imaging to be completely within scala tympani (ST). Performance was assessed using a continuous interleaved sampling (CIS) strategy with 4, 8, 10, and 16 channels and n-of-m with 16 maxima. Listeners were administered auditory tasks of speech understanding [monosyllables, sentences (quiet and +5 dB signal-to-noise ratio, SNR), vowels, consonants], spectral modulation detection, as well as subjective estimates of sound quality. Results were as follows: (1) significant performance gains were observed for speech in quiet (monosyllables and sentences) with 16- as compared to 8-channel CIS, (2) 16 channels in a 16-of-m strategy yielded significantly higher outcomes than 16-channel CIS for sentences in noise (percent correct and subjective sound quality) and spectral modulation detection, (3) 16 channels in a 16-of-m strategy yielded significantly higher outcomes as compared to 8- and 10-channel CIS for monosyllables, sentences (quiet and noise), consonants, spectral modulation detection, and subjective sound quality, (4) 16 versus 8 maxima yielded significantly higher speech recognition for monosyllables and sentences in noise using an n-of-m strategy, and (5) the degree of benefit afforded by 16 versus 8 maxima was inversely correlated with mean electrode-to-modiolus distance. These data demonstrate greater channel independence with perimodiolar electrode arrays as compared to previous studies with straight electrodes and warrant further investigation of the minimum number of maxima and number of channels needed for maximum auditory outcomes.

Structural and functional connectivity of the nondecussating dentato-rubro-thalamic tract.

The dentato-rubro-thalamic tract (DRTT) regulates motor control, connecting the cerebellum to the thalamus. This tract is modulated by deep-brain stimulation in the surgical treatment of medically refractory tremor, especially in essential tremor, where high-frequency stimulation of the thalamus can improve symptoms. The DRTT is classically described as a decussating pathway, ascending to the contralateral thalamus. However, the existence of a nondecussating (i.e. ipsilateral) DRTT in humans was recently demonstrated, and these tracts are arranged in distinct regions of the superior cerebellar peduncle. We hypothesized that the ipsilateral DRTT is connected to specific thalamic nuclei and therefore may have unique functional relevance. The goals of this study were to confirm the presence of the decussating and nondecussating DRTT pathways, identify thalamic termination zones of each tract, and compare whether structural connectivity findings agree with functional connectivity. Diffusion-weighted imaging was used to perform probabilistic tractography of the decussating and nondecussating DRTT in young healthy subjects from the Human Connectome Project (n = 91) scanned using multi-shell diffusion-weighted imaging (270 directions; TR/TE = 5500/89 ms; spatial resolution = 1.25 mm isotropic). To define thalamic anatomical landmarks, a segmentation procedure based on the Morel Atlas was employed, and DRTT targeting was quantified based on the proportion of streamlines arriving at each nucleus. In parallel, functional connectivity analysis was performed using resting-state functional MRI (TR/TE = 720/33 ms; spatial resolution = 2 mm isotropic). It was found that the decussating and nondecussating DRTTs have significantly different thalamic endpoints, with the former preferentially targeting relatively anterior and lateral thalamic nuclei, and the latter connected to more posterior and medial nuclei (p < 0.001). Functional and structural connectivity measures were found to be significantly correlated (r = 0.45, p = 0.031). These findings provide new insight into pathways through which unilateral cerebellum can exert bilateral influence on movement and raise questions about the functional implications of ipsilateral cerebellar efferents.

Variations in Thalamic Anatomy Affect Targeting in Deep Brain Stimulation for Epilepsy.

BACKGROUND: Thalamic size and shape vary significantly across patients - with changes specific to the anterior thalamus occurring with age and in the setting of chronic epilepsy. Such ambiguity raises concerns regarding electrode position and potential implications for seizure outcomes. METHODS: MRIs from 6 patients from a single center underwent quantitative analysis. In addition to direct measurements from postimplantation MRIs, the CRAnialVault Explorer suite was used to normalize electrode position to a common reference system. Relationships between thalamic dimensions, electrode location, and seizure outcome were analyzed. RESULTS: Although this study group was too small to sufficiently power statistical analysis, general trends were identified. There was a trend towards smaller thalamic volumes in nonresponders. Electrode locations demonstrated more variation after normalization. There was a trend towards a more lateral, posterior, and inferior electrode position in nonresponders. CONCLUSIONS: Variations in thalamic shape and volume necessitate direct targeting. Given that changes occur to thalamic anatomy with age and in the setting of epilepsy, improved methods for visualizing and targeting the anterior nucleus are necessary. Pronounced thalamic atrophy may preclude proper electrode placement and serve as a poor prognostic indicator. A greater understanding of thalamic anatomy and connectivity is necessary to optimize deep brain stimulation for epilepsy.

The optimal pallidal target in deep brain stimulation for dystonia: a study using a functional atlas based on nonlinear image registration.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus is established as efficacious for dystonia, yet the optimal target within this structure is not well defined. Published evidence suggests that spatial normalization provides a better estimate of DBS lead location than traditional methods based on standard stereotactic coordinates. METHODS: We retrospectively reviewed our pallidal implanted dystonia population. Patient imaging scans were morphed into an MRI atlas using a nonlinear image registration algorithm. Active contact locations were projected onto the atlas and clusters analyzed for the degree of variance in two groups: (1) good and poor responders and (2) cervical (CD) and generalized dystonia (GD). RESULTS: The average active contact location between CD and GD good responders was distinct but not significantly different. The mean active contact for CD poor responders was significantly different from CD responders and GD poor responders in the dorsoventral direction. CONCLUSIONS: A normalized imaging space is arguably more accurate in visualizing postoperative leads. Despite some separation between groups, this data suggests there was not an optimal pallidal target for common dystonia patients. Degrees of variance overlapped due to a large degree of individual target variation. Patient selection may ultimately be the key to maximizing patient outcomes.

Clinical evaluation of an image-guided cochlear implant programming strategy.

The cochlear implant (CI) has been labeled the most successful neural prosthesis. Despite this success, a significant number of CI recipients experience poor speech understanding, and, even among the best performers, restoration to normal auditory fidelity is rare. While significant research efforts have been devoted to improving stimulation strategies, few developments have led to significant hearing improvement over the past two decades. We have recently introduced image processing techniques that open a new direction for advancement in this field by making it possible, for the first time, to determine the position of implanted CI electrodes relative to the nerves they stimulate using computed tomography images. In this article, we present results of an image-guided, patient-customized approach to stimulation that utilizes the electrode position information our image processing techniques provide. This approach allows us to identify electrodes that cause overlapping stimulation patterns and to deactivate them from a patient's map. This individualized mapping strategy yields significant improvement in speech understanding in both quiet and noise as well as improved spectral resolution in the 68 adult CI recipients studied to date. Our results indicate that image guidance can improve hearing outcomes for many existing CI recipients without requiring additional surgery or the use of 'experimental' stimulation strategies, hardware or software.

Neurologist consistency in interpreting information provided by an interactive visualization software for deep brain stimulation postoperative programming assistance.

INTRODUCTION: Postoperative programming in deep brain stimulation (DBS) therapy for movement disorders can be challenging and time consuming. Providing the neurologist with tools to visualize the electrode location relative to the patient's anatomy along with models of tissue activation and statistical data can therefore be very helpful. In this study, we evaluate the consistency between neurologists in interpreting and using such information provided by our DBS programming assistance software. METHODS: Five neurologists experienced in DBS programming were each given a dataset of 29 leads implanted in 17 patients. For each patient, probabilistic maps of stimulation response, anatomical images, models of tissue activation volumes, and electrode positions were presented inside a software framework called CRAnialVault Explorer (CRAVE) developed in house. Consistency between neurologists in optimal contact selection using the software was measured. RESULTS: With only the efficacy map, the average consistency among the five neurologists with respect to the mode and mean of their selections was 97% and 95%, respectively, while these numbers were 93% and 89%, respectively, when both efficacy and an adverse effect map were used simultaneously. Fleiss' kappa statistic also showed very strong agreement among the neurologists (0.87 when using one map and 0.72 when using two maps). CONCLUSION: Our five neurologists demonstrated high consistency in interpreting information provided by the CRAVE interactive visualization software for DBS postoperative programming assistance. Three of our five neurologists had no prior experience with the software, which suggests that the software has a short learning curve and contact selection is not dependent on familiarity with the program tools.

Focused stimulation of dorsal versus ventral subthalamic nucleus enhances action-outcome learning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the clinical motor symptoms of Parkinson's disease, but may alter the ability to learn contingencies between stimuli, actions and outcomes. We investigated how stimulation of the functional subregions in the subthalamic nucleus (motor and cognitive regions) modulates stimulus-action-outcome learning in Parkinson's disease patients. Twelve Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus completed a probabilistic stimulus-action-outcome task while undergoing ventral and dorsal subthalamic nucleus stimulation (within subjects, order counterbalanced). The task orthogonalized action choice and outcome valence, which created four action-outcome learning conditions: action-reward, inhibit-reward, action-punishment avoidance and inhibit-punishment avoidance. We compared the effects of deep brain stimulation on learning rates across these conditions as well as on computed Pavlovian learning biases. Dorsal stimulation was associated with higher overall learning proficiency relative to ventral subthalamic nucleus stimulation. Compared to ventral stimulation, stimulating the dorsal subthalamic nucleus led to a particular advantage in learning to inhibit action to produce desired outcomes (gain reward or avoid punishment) as well as better learning proficiency across all conditions providing reward opportunities. The Pavlovian reward bias was reduced with dorsal relative to ventral subthalamic nucleus stimulation, which was reflected by improved inhibit-reward learning. Our results show that focused stimulation in the dorsal compared to the ventral subthalamic nucleus is relatively more favourable for learning action-outcome contingencies and reduces the Pavlovian bias that could lead to reward-driven behaviour. Considering the effects of deep brain stimulation of the subthalamic nucleus on learning and behaviour could be important when optimizing stimulation parameters to avoid side effects like impulsive reward-driven behaviour.