Enhancement attacks in biomedical machine learning

The prevalence of machine learning in biomedical research is rapidly growing, yet the trustworthiness of such research is often overlooked. While some previous works have investigated the ability of adversarial attacks to degrade model performance in medical imaging, the ability to falsely improve performance via recently-developed "enhancement attacks" may be a greater threat to biomedical machine learning. In the spirit of developing attacks to better understand trustworthiness, we developed two techniques to drastically enhance prediction performance of classifiers with minimal changes to features: 1) general enhancement of prediction performance, and 2) enhancement of a particular method over another. Our enhancement framework falsely improved classifiers' accuracy from 50% to almost 100% while maintaining high feature similarities between original and enhanced data (Pearson's r's>0.99). Similarly, the method-specific enhancement framework was effective in falsely improving the performance of one method over another. For example, a simple neural network outperformed logistic regression by 17% on our enhanced dataset, although no performance differences were present in the original dataset. Crucially, the original and enhanced data were still similar (r=0.99). Our results demonstrate the feasibility of minor data manipulations to achieve any desired prediction performance, which presents an interesting ethical challenge for the future of biomedical machine learning. These findings emphasize the need for more robust data provenance tracking and other precautionary measures to ensure the integrity of biomedical machine learning research.Comment: 12 pages, 3 figure

Unified Framework for Development, Deployment and Robust Testing of Neuroimaging Algorithms

Developing both graphical and commandline user interfaces for neuroimaging algorithms requires considerable effort. Neuroimaging algorithms can meet their potential only if they can be easily and frequently used by their intended users. Deployment of a large suite of such algorithms on multiple platforms requires consistency of user interface controls, consistent results across various platforms and thorough testing. We present the design and implementation of a novel object-oriented framework that allows for rapid development of complex image analysis algorithms with many reusable components and the ability to easily add graphical user interface controls. Our framework also allows for simplified yet robust nightly testing of the algorithms to ensure stability and cross platform interoperability. All of the functionality is encapsulated into a software object requiring no separate source code for user interfaces, testing or deployment. This formulation makes our framework ideal for developing novel, stable and easy-to-use algorithms for medical image analysis and computer assisted interventions. The technological The framework has been both deployed at Yale and released for public use in the open source multi-platform image analysis software - BioImage Suite (bioimagesuite.org)

Initial validation of a novel method of presurgical language localization through functional connectivity (fcMRI)

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients (12 left) being evaluated for epilepsy surgery at UCLA (mean age 38.9 [sd 11.4]; 6 female; per Wada 14 left language dominant, 1 right, 1 mixed). Language maps were generated using a recently standardized method relying on a conjunction of language tasks (e.g., visual object naming; auditory naming; reading) to identify known language regions (Broca’s area; inferior and superior Wernicke’s Areas; Angular gyrus; Basal Temporal Language Area; Exner’s Area; and Supplementary Speech Area). With activations defined as network nodes, mean network connectivity was compared via permutation tests with alternate (i) fully random and (ii) proximal random networks. Mean network connectivity was determined in independently-acquired motor fMRI datasets (9 foot, 16 hand, 14 tongue). FINDINGS: 77% (30/39) of clinician-derived language networks exhibited mean connectivity greater than fully random networks (p\u3c0.05). Similarly, 69% (27/39) of clinician-derived language networks exhibited mean connectivity greater than proximal random networks (p\u3c0.05). Further analysis of networks not passing the permutation test suggests that low connectivity of non-valid networks may be driven not by low connectivity across all nodes, but by individual nodes that may not actually possess membership within the network. CONCLUSIONS: This study provides preliminary validity for a novel, clinician-based approach to mapping language cortex pre-surgery. This complements our recent work showing this method is reliable, and supports a proposed study comparing fMRI language maps using this technique with the results of direct stimulation mapping

Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children

AbstractBackgroundPreterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections.MethodsLongitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n=13) compared to T children (n=12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group×age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test—revised (PPVT­R), and Rapid Naming Composite (RDRL_Cmp).ResultsNine regions were generated by the group×age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time.ConclusionsThese findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC

Automated brain masking of fetal functional MRI with open data

Fetal resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a critical new approach for characterizing brain development before birth. Despite the rapid and widespread growth of this approach, at present, we lack neuroimaging processing pipelines suited to address the unique challenges inherent in this data type. Here, we solve the most challenging processing step, rapid and accurate isolation of the fetal brain from surrounding tissue across thousands of non-stationary 3D brain volumes. Leveraging our library of 1,241 manually traced fetal fMRI images from 207 fetuses, we trained a Convolutional Neural Network (CNN) that achieved excellent performance across two held-out test sets from separate scanners and populations. Furthermore, we unite the auto-masking model with additional fMRI preprocessing steps from existing software and provide insight into our adaptation of each step. This work represents an initial advancement towards a fully comprehensive, open-source workflow, with openly shared code and data, for fetal functional MRI data preprocessing

Dear reviewers: Responses to common reviewer critiques about infant neuroimaging studies

The field of adult neuroimaging relies on well-established principles in research design, imaging sequences, processing pipelines, as well as safety and data collection protocols. The field of infant magnetic resonance imaging, by comparison, is a young field with tremendous scientific potential but continuously evolving standards. The present article aims to initiate a constructive dialog between researchers who grapple with the challenges and inherent limitations of a nascent field and reviewers who evaluate their work. We address 20 questions that researchers commonly receive from research ethics boards, grant, and manuscript reviewers related to infant neuroimaging data collection, safety protocols, study planning, imaging sequences, decisions related to software and hardware, and data processing and sharing, while acknowledging both the accomplishments of the field and areas of much needed future advancements. This article reflects the cumulative knowledge of experts in the FIT\u27NG community and can act as a resource for both researchers and reviewers alike seeking a deeper understanding of the standards and tradeoffs involved in infant neuroimaging

Dear reviewers: responses to common reviewer critiques about infant neuroimaging studies

The field of adult neuroimaging relies on well-established principles in research design, imaging sequences, processing pipelines, as well as safety and data collection protocols. The field of infant magnetic resonance imaging, by comparison, is a young field with tremendous scientific potential but continuously evolving standards. The present article aims to initiate a constructive dialog between researchers who grapple with the challenges and inherent limitations of a nascent field and reviewers who evaluate their work. We address 20 questions that researchers commonly receive from research ethics boards, grant, and manuscript reviewers related to infant neuroimaging data collection, safety protocols, study planning, imaging sequences, decisions related to software and hardware, and data processing and sharing, while acknowledging both the accomplishments of the field and areas of much needed future advancements. This article reflects the cumulative knowledge of experts in the FIT'NG community and can act as a resource for both researchers and reviewers alike seeking a deeper understanding of the standards and tradeoffs involved in infant neuroimaging.R01 MH104324 - NIMH NIH HHS; UL1 TR001863 - NCATS NIH HHS; P50 MH115716 - NIMH NIH HHS; K01 MH108741 - NIMH NIH HHS; TL1 TR001864 - NCATS NIH HHS; R01 MH118285 - NIMH NIH HHS; U01 MH110274 - NIMH NIH HHS; P50 MH100029 - NIMH NIH HHS; ZIA MH002782 - Intramural NIH HHS; R01 EB027147 - NIBIB NIH HHS; R01 MH119251 - NIMH NIH HHS; UL1 TR003015 - NCATS NIH HHS; F31 HD102156 - NICHD NIH HHS; KL2 TR003016 - NCATS NIH HHS; T32 MH018268 - NIMH NIH HHSPublished versio

Insula as the Interface Between Body Awareness and Movement: A Neurofeedback-Guided Kinesthetic Motor Imagery Study in Parkinson’s Disease

Intentional movement is an internally driven process that requires the integration of motivational and sensory cues with motor preparedness. In addition to the motor cortical-basal ganglia circuits, the limbic circuits are also involved in the integration of these cues. Individuals with Parkinson’s disease (PD) have a particular difficulty with internally generating intentional movements and maintaining the speed, size, and vigor of movements. This difficulty improves when they are provided with external cues suggesting that there is a problem with the internal motivation of movement in PD. The prevailing view attributes this difficulty in PD to the dysfunction of motor cortical-basal ganglia circuits. First, we argue that the standard cortical-basal ganglia circuit model of motor dysfunction in PD needs to be expanded to include the insula which is a major hub within the limbic circuits. We propose a neural circuit model highlighting the interaction between the insula and dorsomedial frontal cortex which is involved in generating intentional movements. The insula processes a wide range of sensory signals arising from the body and integrates them with the emotional and motivational context. In doing so, it provides the impetus to the dorsomedial frontal cortex to initiate and sustain movement. Second, we present the results of our proof-of-concept experiment demonstrating that the functional connectivity of the insula-dorsomedial frontal cortex circuit can be enhanced with neurofeedback-guided kinesthetic motor imagery using functional magnetic resonance imaging in subjects with PD. Specifically, we found that the intensity and quality of body sensations evoked during motor imagery and the emotional and motivational context of motor imagery determined the direction (i.e., negative or positive) of the insula-dorsomedial frontal cortex functional connectivity. After 10–12 neurofeedback sessions and “off-line” practice of the successful motor imagery strategies all subjects showed a significant increase in the insula-dorsomedial frontal cortex functional connectivity. Finally, we discuss the implications of these results regarding motor function in patients with PD and propose suggestions for future studies

An ode to fetal, infant, and toddler neuroimaging: chronicling early clinical to research applications with MRI, and an introduction to an academic society connecting the field

Fetal, infant, and toddler neuroimaging is commonly thought of as a development of modern times (last two decades). Yet, this field mobilized shortly after the discovery and implementation of MRI technology. Here, we provide a review of the parallel advancements in the fields of fetal, infant, and toddler neuroimaging, noting the shifts from clinical to research use, and the ongoing challenges in this fast-growing field. We chronicle the pioneering science of fetal, infant, and toddler neuroimaging, highlighting the early studies that set the stage for modern advances in imaging during this developmental period, and the large-scale multi-site efforts which ultimately led to the explosion of interest in the field today. Lastly, we consider the growing pains of the community and the need for an academic society that bridges expertise in developmental neuroscience, clinical science, as well as computational and biomedical engineering, to ensure special consideration of the vulnerable mother-offspring dyad (especially during pregnancy), data quality, and image processing tools that are created, rather than adapted, for the young brain.UL1 TR001863 - NCATS NIH HHS; R01 MH117983 - NIMH NIH HHS; K24 MH127381 - NIMH NIH HHS; UL1 TR001873 - NCATS NIH HHS; TL1 TR001875 - NCATS NIH HHS; T32 MH018268 - NIMH NIH HHS; ZIA MH002782 - Intramural NIH HHS; UL1 TR003015 - NCATS NIH HHS; KL2 TR003016 - NCATS NIH HHS; R01 HD065762 - NICHD NIH HHS; R03 EB022754 - NIBIB NIH HHS; R21 HD095338 - NICHD NIH HHS; R01 HD093578 - NICHD NIH HHS; R01 HD099846 - NICHD NIH HHS; R01 HD100560 - NICHD NIH HHSPublished versio