Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning.

Disability progression in multiple sclerosis remains resistant to treatment. The absence of a suitable biomarker to allow for phase 2 clinical trials presents a high barrier for drug development. We propose to enable short proof-of-concept trials by increasing statistical power using a deep-learning predictive enrichment strategy. Specifically, a multi-headed multilayer perceptron is used to estimate the conditional average treatment effect (CATE) using baseline clinical and imaging features, and patients predicted to be most responsive are preferentially randomized into a trial. Leveraging data from six randomized clinical trials (n = 3,830), we first pre-trained the model on the subset of relapsing-remitting MS patients (n = 2,520), then fine-tuned it on a subset of primary progressive MS (PPMS) patients (n = 695). In a separate held-out test set of PPMS patients randomized to anti-CD20 antibodies or placebo (n = 297), the average treatment effect was larger for the 50% (HR, 0.492; 95% CI, 0.266-0.912; p = 0.0218) and 30% (HR, 0.361; 95% CI, 0.165-0.79; p = 0.008) predicted to be most responsive, compared to 0.743 (95% CI, 0.482-1.15; p = 0.179) for the entire group. The same model could also identify responders to laquinimod in another held-out test set of PPMS patients (n = 318). Finally, we show that using this model for predictive enrichment results in important increases in power.

Mapping the human auditory cortex using spectrotemporal receptive fields generated with magnetoencephalography.

We present a novel method to map the functional organization of the human auditory cortex noninvasively using magnetoencephalography (MEG). More specifically, this method estimates via reverse correlation the spectrotemporal receptive fields (STRF) in response to a temporally dense pure tone stimulus, from which important spectrotemporal characteristics of neuronal processing can be extracted and mapped back onto the cortex surface. We show that several neuronal populations can be found examining the spectrotemporal characteristics of their STRFs, and demonstrate how these can be used to generate tonotopic gradient maps. In doing so, we show that the spatial resolution of MEG is sufficient to reliably extract important information about the spatial organization of the auditory cortex, while enabling the analysis of complex temporal dynamics of auditory processing such as best temporal modulation rate and response latency given its excellent temporal resolution. Furthermore, because spectrotemporally dense auditory stimuli can be used with MEG, the time required to acquire the necessary data to generate tonotopic maps is significantly less for MEG than for other neuroimaging tools that acquire BOLD-like signals.

The neurologist's role in disabling multiple sclerosis: A qualitative study of patient and care provider perspectives.

BACKGROUND: Patients with advanced, disabling multiple sclerosis (MS) have few effective treatment options. Little is known about the role that patients and their care providers want their neurologist to fill in this situation. OBJECTIVE: To better understand the role that patients with disabling MS and their care providers want their neurologist to have in their care. METHODS: In this exploratory qualitative study, we conducted semi-structured interviews with 29 participants (19 patients with severe disability due to MS and 10 care providers). Interview transcripts were analyzed using inductive thematic analysis. RESULTS: Participants identified three main roles for their neurologist: a source of hope for therapeutic advances, an educator about the disease and its management, and a source of support. CONCLUSION: Despite sustaining a level of disability that may be refractory to standard medical therapy, patients with disabling MS and care providers continue to value certain roles of their neurologist. The neurologist's role as a source of hope and support in particular has not received enough attention in the literature.