Multiple surgical targets for treating obsessive-compulsive disorder with deep brain stimulation (DBS) have been proposed. However, different targets may modulate the same neural network responsible ...for clinical improvement. We analyzed data from four cohorts of patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens or the subthalamic nucleus (STN). The same fiber bundle was associated with optimal clinical response in cohorts targeting either structure. This bundle connected frontal regions to the STN. When informing the tract target based on the first cohort, clinical improvements in the second could be significantly predicted, and vice versa. To further confirm results, clinical improvements in eight patients from a third center and six patients from a fourth center were significantly predicted based on their stimulation overlap with this tract. Our results show that connectivity-derived models may inform clinical improvements across DBS targets, surgeons and centers. The identified tract target is openly available in atlas form.
Parkinson's disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit ...and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21-30 Hz) but not low (13-21 Hz) beta frequency range correlated with 'hyperdirect pathway' fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.
Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical ...fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.
High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.
All patients responded well to treatment (46% mean improvement off medication UPDRS-III p < 0.0001) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = −10(−9.5), Y = −13(-1) and Z = −7(−3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.
These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
•Optimal DBS tissue activation areas are identified in the subthalamic nucleus.•Stimulation in the supero-lateral subthalamic nucleus is most effective.•Connectivity pattern predicts improvement in cardinal symptoms in Parkinson's.
Surgical interventions are used for trigeminal neuralgia when drug treatment fails. Surgical treatments divide into two main categories, ablative (destructive) or non-ablative. These treatments can ...be done at three different sites: peripherally, at the Gasserian ganglion level, and within the posterior fossa of the skull.
To assess the efficacy of neurosurgical interventions for classical trigeminal neuralgia in terms of pain relief, quality of life and any harms. To determine if there are defined subgroups of patients more likely to benefit.
We searched the Cochrane Neuromuscular Disease Group Specialized Register, (13 May 2010), CENTRAL (issue 2, 2010 part of the Cochrane Library), Health Technology Assessment (HTA) Database, NHS Economic Evaluation Database (NHSEED) and Database of Abstracts of Reviews of Effects (DARE) (issue 4, 2010 (HTA, NHSEED and DARE are part of the Cochrane Library)), MEDLINE (January 1966 to May 2010) and EMBASE (January 1980 to May 2010) with no language exclusion.
Randomised controlled trials and quasi-randomised controlled trials of neurosurgical interventions used in the treatment of classical trigeminal neuralgia.
Two authors independently assessed trial quality and extracted data. We contacted authors for clarification and missing information whenever possible.
Eleven studies involving 496 participants met some of the inclusion criteria stated in the protocol. One hundred and eighty patients in five studies had peripheral interventions, 229 patients in five studies had percutaneous interventions applied to the Gasserian ganglion, and 87 patients in one study underwent two modalities of stereotactic radiosurgery (Gamma Knife) treatment. No studies addressing microvascular decompression (which is the only non-ablative procedure) met the inclusion criteria. All but two of the identified studies had a high to medium risk of bias because of either missing data or methodological inconsistency. It was not possible to undertake meta-analysis because of differences in the intervention modalities and variable outcome measures. Three studies had sufficient outcome data for analysis. One trial, which involved 40 participants, compared two techniques of radiofrequency thermocoagulation (RFT) of the Gasserian ganglion at six months. Pulsed RFT resulted in return of pain in all participants by three months. When this group were converted to conventional (continuous) treatment these participants achieved pain control comparable to the group that had received conventional treatment from the outset. Sensory changes were common in the continuous treatment group. In another trial, of 87 participants, investigators compared radiation treatment to the trigeminal nerve at one or two isocentres in the posterior fossa. There were insufficient data to determine if one technique was superior to another. Two isocentres increased the incidence of sensory loss. Increased age and prior surgery were predictors for poorer pain relief. Relapses were nonsignificantly reduced with two isocentres (risk ratio (RR) 0.72, 95% confidence intervaI (CI) 0.30 to 1.71). A third study compared two techniques for RFT in 54 participants for 10 to 54 months. Both techniques produced pain relief (not significantly in favour of neuronavigation (RR 0.70, 95% CI 0.46 to 1.04) but relief was more sustained and side effects fewer if a neuronavigation system was used. The remaining eight studies did not report outcomes as predetermined in our protocol.
There is very low quality evidence for the efficacy of most neurosurgical procedures for trigeminal neuralgia because of the poor quality of the trials. All procedures produced variable pain relief, but many resulted in sensory side effects. There were no studies of microvascular decompression which observational data suggests gives the longest pain relief. There is little evidence to help comparative decision making about the best surgical procedure. Well designed studies are urgently needed.
Spinal cord stimulation (SCS) is a therapeutic procedure widely used in the management of refractory chronic pain. Evidence from case reports and small descriptive studies has emerged suggesting a ...role for SCS in patients with gait dysfunction, such as freezing of gait (FoG) and postural imbalance. These are severely debilitating symptoms of advanced Parkinson's disease (PD).
To establish the current evidence base for the potential application of SCS on gait and balance dysfunction in PD patients.
Three online databases were screened for relevant manuscripts. Two separate searches and four different search strategies were applied to yield relevant results. The main parameters of interest were postural and gait symptoms; secondary outcomes were Quality of Life (QoL) and adverse effects.
Nineteen studies fulfilled the inclusion criteria. Motor improvements using section III of the Unified Parkinson's Disease Rating Score (UPDRS-III) were available in 13 studies. Measurements to assess FoG reported the following improvements: FoG questionnaires (in 1/19 studies); generalized freezing parameters (2); and walkway/wireless accelerometer measurements (2). Parameters of postural imbalance and falling improved as follows: BBS (1); posture sagittal vertical axis (1); and generalized data on postural instability (8). Two studies reported on adverse effects. QoL was shown to improve as follows: EQ-5D (2); ADL (1); SF-36 (1); BDI-II (1); PDQ-8 (1); HDRS (1); and VAS (5).
SCS may have a therapeutic potential in advanced PD patients suffering from postural and gait-related symptoms. The existing evidence suggests that SCS positively affects patients' QoL with an acceptable safety profile in this patient population.
Brain connectivity profiles seeding from deep brain stimulation (DBS) electrodes have emerged as informative tools to estimate outcome variability across DBS patients. Given the limitations of ...acquiring and processing patient-specific diffusion-weighted imaging data, a number of studies have employed normative atlases of the human connectome. To date, it remains unclear whether patient-specific connectivity information would strengthen the accuracy of such analyses. Here, we compared similarities and differences between patient-specific, disease-matched and normative structural connectivity data and their ability to predict clinical improvement.
Data from 33 patients suffering from Parkinson's Disease who underwent surgery at three different centers were retrospectively collected. Stimulation-dependent connectivity profiles seeding from active contacts were estimated using three modalities, namely patient-specific diffusion-MRI data, age- and disease-matched or normative group connectome data (acquired in healthy young subjects). Based on these profiles, models of optimal connectivity were calculated and used to estimate clinical improvement in out of sample data.
All three modalities resulted in highly similar optimal connectivity profiles that could largely reproduce findings from prior research based on this present novel multi-center cohort. In a data-driven approach that estimated optimal whole-brain connectivity profiles, out-of-sample predictions of clinical improvements were calculated. Using either patient-specific connectivity (R = 0.43 at p = 0.001), an age- and disease-matched group connectome (R = 0.25, p = 0.048) and a normative connectome based on healthy/young subjects (R = 0.31 at p = 0.028), significant predictions could be made.
Our results of patient-specific connectivity and normative connectomes lead to similar main conclusions about which brain areas are associated with clinical improvement. Still, although results were not significantly different, they hint at the fact that patient-specific connectivity may bear the potential of explaining slightly more variance than group connectomes. Furthermore, use of normative connectomes involves datasets with high signal-to-noise acquired on specialized MRI hardware, while clinical datasets as the ones used here may not exactly match their quality. Our findings support the role of DBS electrode connectivity profiles as a promising method to investigate DBS effects and to potentially guide DBS programming.
•Connectivity-based Vim position varied markedly between subjects and from atlas-defined coordinates.•This positional variability was not related to any methodological confound tested.•Hemispheric ...asymmetry was observed in connectivity-based Vim position.•We hypothesise lateralization of cerebellar functions, such as language, may contribute to asymmetry.•Knowledge of Vim position variability could help inform neurosurgical planning in the management of tremor.
The ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results.
Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim) in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds.
We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.88 mm (left) and 2.12 mm (right) of the average midpoint and 3.98 mm (left) and 5.41 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTC reconstructed. The method was reproducible, with no significant cd-Vim location differences in a separate test-retest cohort. The superior cerebellar peduncle was identified as a potential source of artificial variance.
This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based coordinate targeting fails to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; these findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor.
Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson's disease (PD) insufficiently controlled with medical therapies. ...This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording.
A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8-11 years. Motor status was evaluated using part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes.
STN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively.
Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.
•Connectomics can help treatment planning in epilepsy and neuro-oncology.•Tractography can help motor thalamus targeting and has potential with other targets.•Combined with other modalities, ...connectomics can help elucidate pathophysiology.•Lack of standards in image acquisition and processing limit widespread utilization.•Improved acquisition and process automation can increase reliability of these tools.
Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pathological processes and treatments as well as prognostic biomarkers. These tools have the real potential to inform patient-specific treatment strategies. Nevertheless, a realistic appraisal of clinical utility is needed that balances the growing excitement and interest in the field with important limitations associated with these techniques. Quality of the raw data, minutiae of the processing methodology, and the statistical models applied can all impact on the results and their interpretation. A lack of standardization in data acquisition and processing has also resulted in issues with reproducibility. This limitation has had a direct impact on the reliability of these tools and ultimately, confidence in their clinical use. Advances in MRI technology and computational power as well as automation and standardization of processing methods, including machine learning approaches, may help address some of these issues and make these tools more reliable in clinical use. In this review, we will highlight the current clinical uses of MRI connectomics in the diagnosis and treatment of neurological disorders; balancing emerging applications and technologies with limitations of connectivity analytic approaches to present an encompassing and appropriate perspective.
The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease ...(PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.
•The thalamic target for surgery for tremor is not readily visible on conventional MRI.•Probabilistic tractography is used to segment the thalamus based on connectivity.•The best target area is connected to the contralateral dentate cerebellar nucleus.•GPU processing is used to segment the thalamus in a clinically feasible timescale.•This technique can map out the DRT tract with clear mesencephalic crossing.
PDF
