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Questionable science and reproducibility in electrical brain stimulation research.

ABSTRACT: Electrical brain stimulation (EBS) is a trendy new technique used to change brain function and treat neurological, psychiatric and psychological disorders. We were curious whether the published literature, which is dominated by positive results, reflects the experience of researchers using EBS. Specifically, we wanted to know whether researchers are able to reproduce published EBS effects and whether they engage in, but fail to report, questionable research practices. We invited 976 researchers to complete an online survey. We also audited 100 randomly-selected published EBS papers. A total of 154 researchers completed the survey. Survey respondents had a median of 3 [1 to 6, IQR] published EBS papers (1180 total) and 2 [1 to 3] unpublished ones (380 total). With anodal and cathodal EBS, the two most widely used techniques, 45-50% of researchers reported being able to routinely reproduce published results. When asked about how study sample size was determined, 69% of respondents reported using the sample size of published studies, while 61% had used power calculations, and 32% had based their decision on pilot data. In contrast, our audit found only 6 papers where power calculations were used and a single paper in which pilot data was used. When asked about questionable research practices, survey respondents were aware of other researchers who selectively reported study outcomes (41%) and experimental conditions (36%), adjusted statistical analysis to optimise results (43%), and engaged in other shady practices (20%). Fewer respondents admitted to engaging in these practices themselves, although 25% admitted to adjusting statistical analysis to optimize results. There was strong agreement that such practices should be reported in research papers; however, our audit found only two such admissions. The present survey confirms that questionable research practices and poor reproducibility are present in EBS studies. The belief that EBS is effective needs to be replaced by a more rigorous approach so that reproducible brain stimulation methods can be devised and applied.

SUBMITTER: Heroux ME

PROVIDER: S-EPMC5405934 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Questionable science and reproducibility in electrical brain stimulation research.

Héroux Martin E ME Loo Colleen K CK Taylor Janet L JL Gandevia Simon C SC

PloS one 20170426 4

Electrical brain stimulation (EBS) is a trendy new technique used to change brain function and treat neurological, psychiatric and psychological disorders. We were curious whether the published literature, which is dominated by positive results, reflects the experience of researchers using EBS. Specifically, we wanted to know whether researchers are able to reproduce published EBS effects and whether they engage in, but fail to report, questionable research practices. We invited 976 researchers ...[more]

PMID: 28445482

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Project description:Demand-controlled deep brain stimulation (DBS) appears to be a promising approach for the treatment of Parkinson's disease (PD) as revealed by computational, pre-clinical and clinical studies. Stimulation delivery is adapted to brain activity, for example, to the amount of neuronal activity considered to be abnormal. Such a closed-loop stimulation setup might help to reduce the amount of stimulation current, thereby maintaining therapeutic efficacy. In the context of the development of stimulation techniques that aim to restore desynchronized neuronal activity on a long-term basis, specific closed-loop stimulation protocols were designed computationally. These feedback techniques, e.g., pulsatile linear delayed feedback (LDF) or pulsatile nonlinear delayed feedback (NDF), were computationally developed to counteract abnormal neuronal synchronization characteristic for PD and other neurological disorders. By design, these techniques are intrinsically demand-controlled methods, where the amplitude of the stimulation signal is reduced when the desired desynchronized regime is reached. We here introduce a novel demand-controlled stimulation method, pulsatile multisite linear delayed feedback (MLDF), by employing MLDF to modulate the pulse amplitude of high-frequency (HF) DBS, in this way aiming at a specific, MLDF-related desynchronizing impact, while maintaining safety requirements with the charge-balanced HF DBS. Previously, MLDF was computationally developed for the control of spatio-temporal synchronized patterns and cluster states in neuronal populations. Here, in a physiologically motivated model network comprising neurons from subthalamic nucleus (STN) and external globus pallidus (GPe), we compare pulsatile MLDF to pulsatile LDF for the case where the smooth feedback signals are used to modulate the amplitude of charge-balanced HF DBS and suggest a modification of pulsatile MLDF which enables a pronounced desynchronizing impact. Our results may contribute to further clinical development of closed-loop DBS techniques.

Project description:Neurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level. We used 4137 DES points derived from 612 glioma patients in combination with human connectome data-resting-state functional MRI, n = 1000 and diffusion weighted imaging, n = 284-to provide a multimodal description of the causal macroscale functional networks subtending 12 distinct behavioural domains. To probe the validity of our procedure, we (i) compared the network topographies of healthy and clinical populations; (ii) tested the predictive capacity of DES-derived networks; (iii) quantified the coupling between structural and functional connectivity; and (iv) built a multivariate model able to quantify single subject deviations from a normative population. Lastly, we probed the translational potential of DES-derived functional networks by testing their specificity and sensitivity in identifying critical neuromodulation targets and neural substrates associated with postoperative language deficits. The combination of DES and human connectome data resulted in an average 29.4-fold increase in whole brain coverage compared to DES alone. DES-derived functional networks are predictive of future stimulation points (97.8% accuracy) and strongly supported by the anatomical connectivity of subcortical stimulations. We did not observe any significant topographical differences between the patients and the healthy population at both group and single subject level. Showcasing concrete clinical applications, we found that DES-derived functional networks overlap with effective neuromodulation targets across several functional domains, show a high degree of specificity when tested with the intracranial stimulation points of a different stimulation technique and can be used effectively to characterize postoperative behavioural deficits. The integration of DES with the human connectome fundamentally advances the quality of the functional mapping provided by DES or functional imaging alone. DES-derived functional networks can reliably predict future stimulation points, have a strong correspondence with the underlying white matter and can be used for patient specific functional mapping. Possible applications range from psychiatry and neurology to neuropsychology, neurosurgery and neurorehabilitation.

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Questionable science and reproducibility in electrical brain stimulation research.

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Questionable science and reproducibility in electrical brain stimulation research.

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