Explainable deep learning models for dementia identification via magnetic resonance imaging : Developing topics

Abstract Background Today, to diagnose dementia, clinicians evaluate cognitive tests performed by patients and briefly analyze brain imaging data to look for biomarkers. While valuable information is present in MRI scans, these latter remain challenging to analyze and interpret. Artificial intelligence models have shown promising results to improve the current practice by supporting practitioners in the evaluation of imaging data. Nonetheless, the majority of developed statistical models are more often than not black-box systems that issue predictions without any clear interpretability, hindering their practical applications. Methods We propose an interpretable method based on deep learning that works on minimally preprocessed T1-weighted 3D scans of the brain. Relying on FullGrad [1], we can dissect the predictions of the model given an input scan. Once the model is trained, it can not only give an automated diagnostic but also generate a heatmap highlighting the regions of the brain that our model points to be responsible for its prediction of dementia. To ensure practicality, we integrate our model in a convenient app that can smoothly be run from a browser, as shown in the attached screenshot. Results We trained and evaluated our model on the OASIS dataset [2]. The specific explanation obtained by our model points at well-known biomarkers, notably by highlighting the voxels of the hippocampus of patients with dementia. Interestingly, as it can be seen in the second annex, we notice that across individuals, our model focuses more on the voxels located in the right hippocampus. Conclusions In this study, we show how machine learning can identify dementia patients using MRI images while ensuring interpretable decisions of the models. Our tools, including the bespoke 'explainer' viewer overlaid on each patient's brain, will enable the development of better and more reliable machine-learning based diagnostics and nurture the trust of practitioners in computer-aided diagnostics. Furthermore, this will help to discover currently unknown biomarkers and thus lead to a better understanding of the disease. References: 1) Full-Gradient Representation for Neural Network Visualization, Suraj Srinivas, Francois Fleuret, 2) OASIS-3: Longitudinal Neuroimaging, Clinical, and Cognitive Dataset for Normal Aging and Alzheimer Disease, Pamela J LaMontagne

Grey matter alterations co-localize with functional abnormalities in developmental dyslexia : an ALE meta-analysis

The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions

Functional compensation of motor function in pre-symptomatic Huntington's disease

Involuntary choreiform movements are a clinical hallmark of Huntington's disease. Studies in clinically affected patients suggest a shift of motor activations to parietal cortices in response to progressive neurodegeneration. Here, we studied pre-symptomatic gene carriers to examine the compensatory mechanisms that underlie the phenomenon of retained motor function in the presence of degenerative change. Fifteen pre-symptomatic gene carriers and 12 matched controls performed button presses paced by a metronome at either 0.5 or 2 Hz with four fingers of the right hand whilst being scanned with functional magnetic resonance imaging. Subjects pressed buttons either in the order of a previously learnt 10-item finger sequence, from left to right, or kept still. Error rates ranged from 2% to 7% in the pre-symptomatic gene carriers and from 0.5% to 4% in controls, depending on the condition. No significant difference in task performance was found between groups for any of the conditions. Activations in the supplementary motor area (SMA) and superior parietal lobe differed with gene status. Compared with healthy controls, gene carriers showed greater activations of left caudal SMA with all movement conditions. Activations correlated with increasing speed of movement were greater the closer the gene carriers were to estimated clinical diagnosis, defined by the onset of unequivocal motor signs. Activations associated with increased movement complexity (i.e. with the pre-learnt 10-item sequence) decreased in the rostral SMA with nearing diagnostic onset. The left superior parietal lobe showed reduced activation with increased movement complexity in gene carriers compared with controls, and in the right superior parietal lobe showed greater activations with all but the most demanding movements. We identified a complex pattern of motor compensation in pre-symptomatic gene carriers. The results show that preclinical compensation goes beyond a simple shift of activity from premotor to parietal regions involving multiple compensatory mechanisms in executive and cognitive motor areas. Critically, the pattern of motor compensation is flexible depending on the actual task demands on motor contro

Integrating Core Conflictual Relationship Themes in neurobiological assessment of interpersonal processes in psychotherapy

Interpersonal processes are a key target in counselling and psychotherapy. It is of paramount importance to sharpen their assessment using integrated methods. Hence, this methodological paper describes how fields of research in psychotherapy and neuroimaging can be integrated into one novel complementary neurobehavioural paradigm that can be applied to enhance our understanding of interpersonal processes in psychotherapy. To illustrate this integration, we present selected data from a pre–post pilot study where the authors assessed interpersonal processes in brief treatment for borderline personality disorder using the core conflictual relationship theme, functional magnetic resonance imaging (fMRI) and outcome questionnaires. To do so, they measured individual changes in neural activity using an fMRI task pre‐ and post‐treatment where clients gave feedback on the emotional valence of sentences extracted from their own Relationship Anecdotes Paradigm interviews mixed with neutral ones. In this paper, using data from two participants of said study, we discuss how to implement this methodology and what can be achieved in terms of results

Sustained enhancements in inhibitory control depend primarily on the reinforcement of fronto-basal anatomical connectivity

What are the neurophysiological determinants of sustained supra-normal inhibitory control performance? We addressed this question by coupling multimodal neuroimaging and behavioral investigations of experts in fencing who underwent more than 20,000 h of inhibitory control training over 15 years. The superior control of the experts manifested behaviorally as a speeding-up of inhibition processes during a Go/NoGo task and was accompanied by changes in bilateral inferior frontal white matter microstructure. In the expert group, inhibition performance correlated positively with the fractional anisotropy (FA) of white matter tracts projecting to the basal ganglia, and the total training load with the FA in supplementary motor areas. Critically, the experts showed no changes in grey matter volume or in the functional organization of the fronto-basal inhibitory control network. The fencers’ performance and neural activity during a 2-back working memory task did not differ from those of the controls, ensuring that their expertise was specific to inhibitory control. Our results indicate that while phasic changes in the patterns of neural activity and grey matter architecture accompany inhibitory control improvement after short- to medium- term training, long- lasting inhibitory control improvements primarily depend on the reinforcement of fronto- basal structural connectivity

The Combination of DAT-SPECT, Structural and Diffusion MRI Predicts Clinical Progression in Parkinson’s Disease

There is an increasing interest in identifying non-invasive biomarkers of disease severity and prognosis in idiopathic Parkinson’s disease (PD). Dopamine-transporter SPECT (DAT-SPECT), diffusion tensor imaging (DTI), and structural magnetic resonance imaging (sMRI) provide unique information about the brain’s neurotransmitter and microstructural properties. In this study, we evaluate the relative and combined capability of these imaging modalities to predict symptom severity and clinical progression in de novo PD patients. To this end, we used MRI, SPECT, and clinical data of de novo drug-naïve PD patients (n = 205, mean age 61 ± 10) and age-, sex-matched healthy controls (n = 105, mean age 58 ± 12) acquired at baseline. Moreover, we employed clinical data acquired at 1 year follow-up for PD patients with or without L-Dopa treatment in order to predict the progression symptoms severity. Voxel-based group comparisons and covariance analyses were applied to characterize baseline disease-related alterations for DAT-SPECT, DTI, and sMRI. Cortical and subcortical alterations in de novo PD patients were found in all evaluated imaging modalities, in line with previously reported midbrain-striato-cortical network alterations. The combination of these imaging alterations was reliably linked to clinical severity and disease progression at 1 year follow-up in this patient population, providing evidence for the potential use of these modalities as imaging biomarkers for disease severity and prognosis that can be integrated into clinical trials

Neuroticism, depression, and anxiety traits exacerbate the state of cognitive impairment and hippocampal vulnerability to Alzheimer's disease

Certain personality traits are associated with higher risk of Alzheimer's disease, similar to cognitive impairment. The identification of biological markers associated with personality in mild cognitive impairment could advance the early detection of Alzheimer's disease

Mechanisms of change in brief treatments for borderline personality disorder: a protocol of a randomized controlled trial

Borderline personality disorder (BPD) is one of the most frequent, most debilitating and lethal mental conditions and is associated with a serious burden of disease. Treatment for patients with BPD involves structured psychotherapy, and may involve brief psychiatric treatment as first-line intervention. No controlled study has assessed the effectiveness of such brief intervention. Whereas most psychotherapy studies in patients with BPD focus on the effectiveness of the intervention, we still lack an understanding of how and why these effects are produced from a patient process perspective. It is therefore of utmost importance to study the treatment-underlying mechanisms of change. The present study plans to apply novel measurement methods for assessing change in two central psychobiological processes in BPD: emotion and socio-cognitive processing. The study uses theory-driven and ecologically valid experimental tasks, which take the patient's individual experience as the anchor, by integrating methodology from psychotherapy process and neurofunctional imagery research. The aim of this two-arm, randomized controlled study is to test the effects (i.e., symptom reduction) and the underlying mechanisms of change associated with a brief psychiatric treatment (10 sessions over 4 months), compared with treatment as usual. Participants (N = 80 patients with BPD) undergo assessments at four points (intake, 2 months, discharge, and 12-month follow up). In addition to symptom measures, individuals undergo a 2-step assessment for the potential mechanisms of change (i.e., emotion and socio-cognitive processing): (1) behavioral and (2) (for a sub-sample) neurofunctional. We hypothesize that change in the mechanisms explains the treatment effects. This study uses an easy-to-implement treatment of BPD, and a sophisticated assessment procedure to demonstrate the critical role of psychobiological change in emotion and socio-cognitive processing in brief treatments. It will help increase the effectiveness of brief treatment for BPD and help diminish the societal burden of disease related to BPD, in these early stages of treatment. TRIAL REGISTRATION {2}: ClinicalTrials.gov: NCT03717818. Registered on 24 October 2018). Protocol version {3} number 2 from 9 February 2018

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atroph