Cortical thickness in the right anterior cingulate cortex relates to clinical response to left prefrontal accelerated intermittent theta burst stimulation : an exploratory study

Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed. Materials and Methods: Here, the relation between cortical thickness and clinical response (17‐item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham‐controlled, double‐blinded, cross‐over aiTBS design (NCT01832805). Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses. Conclusion: Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC

Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

© 2018 The Author(s). Background: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. Methods: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged =45 years and have experienced knee pain =4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. Discussion: This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001595303, date of registration 1/12/2017

Personalizing repetitive transcranial magnetic stimulation parameters for depression treatment using multimodal neuroimaging

Repetitive transcranial magnetic stimulation (rTMS) is a tool that can be used to administer treatment for neuropsychiatric disorders such as major depressive disorder, although the clinical efficacy is still rather modest. Overly general stimulation protocols that consider neither patient-specific depression symptomology nor individualized brain characteristics, such as anatomy or structural and functional connections, may be the cause of the high inter- and intraindividual variability in rTMS clinical responses. Multimodal neuroimaging can provide the necessary insights into individual brain characteristics and can therefore be used to personalize rTMS parameters. Optimal coil positioning should include a three-step process: 1) identify the optimal (indirect) target area based on the exact symptom pattern of the patient; 2) derive the cortical (direct) target location based on functional and/or structural connectomes derived from functional and diffusion magnetic resonance imaging data; and 3) determine the ideal coil position by computational modeling, such that the electric field distribution overlaps with the cortical target. These TMS-induced electric field simulations, derived from anatomical and diffusion magnetic resonance imaging data, can be further applied to compute optimal stimulation intensities. In addition to magnetic resonance imaging, electroencephalography can provide complementary information regarding the ongoing brain oscillations. This information can be used to determine the optimal timing and frequency of the stimuli. The heightened benefits of these personalized stimulation approaches are logically reasoned, but speculative. Randomized clinical trials will be required to compare clinical responses from standard rTMS protocols to personalized protocols. Ultimately, an optimized clinical response may result from precision protocols derived from combinations of personalized stimulation parameters

Does electrode localization in tDCS research matter? A comparison between 10–20 EEG system and MRI-guided neuronavigation

Although the 10–20 EEG system is frequently used to locate the dorsolateral prefrontal cortex (DLPFC) in tDCS research, due to intersubject brain variability, this method may have limited target accuracy and may result in suboptimal stimulation. To address this issue, we compared left DLPFC-localization via the 10–20 EEG system to MRI-guided neuronavigation in forty healthy female participants within the same age range. Compared to the 10–20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly. Furthermore, tDCS-induced electric fields (derived from one subject) suggest that these different localization methods induce different electric fields in distinct brain regions. Our findings indicate that prefrontal tDCS targeting methods result in distinct electrode localizations, each of which suggested being associated to unique underlying electric field distributions. Considering the frequent use of tDCS in research, an evaluation and direct comparison of the outcome of both targeting methods is therefore warranted

Non-invasive brain stimulation : from field modeling to neuronal activation

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are the most commonly studied non-invasive brain stimulation treatment options. Over the past years, modeling and simulation of stimulation-induced electric fields have received increased attention. Modeling can take place at three different levels of abstraction. Although some validation of these models has taken place at these levels separately, coupling between the levels through a multi-scale approach and experimental validation of the overall approach has only recently started. This specific coupling might be an important step to unravel the mechanism of action and to ultimately improve the clinical efficacy of non-invasive brain stimulation

Recent advances in the use of focused ultrasound as a treatment for epilepsy

Epilepsy affects about 1% of the population. Approximately one third of patients with epilepsy are drug-resistant (DRE). Resective surgery is an effective treatment for DRE, yet invasive, and not all DRE patients are suitable resective surgery candidates. Focused ultrasound, a novel non-invasive neurointerventional method is currently under investigation as a treatment alternative for DRE. By emitting one or more ultrasound waves, FUS can target structures in the brain at millimeter resolution. High intensity focused ultrasound (HIFU) leads to ablation of tissue and could therefore serve as a non-invasive alternative for resective surgery. It is currently under investigation in clinical trials following the approval of HIFU for essential tremor and Parkinson’s disease. Low intensity focused ultrasound (LIFU) can modulate neuronal activity and could be used to lower cortical neuronal hyper-excitability in epilepsy patients in a non-invasive manner. The seizure-suppressive effect of LIFU has been studied in several preclinical trials, showing promising results. Further investigations are required to demonstrate translation of preclinical results to human subjects

The road towards personalized medicine : increasing the effects of brain stimulation using individual characteristics

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