Large-scale screening of clinical assessments to distinguish between states in the Integrated HD Progression Model (IHDPM).

Background: Understanding the sensitivity and utility of clinical assessments across different HD stages is important for study/trial endpoint selection and clinical assessment development. The Integrated HD Progression Model (IHDPM) characterizes the complex symptom progression of HD and separates the disease into nine ordered disease states. Objective: To generate a temporal map of discriminatory clinical measures across the IHDPM states. Methods: We applied the IHDPM to all HD individuals in an integrated longitudinal HD dataset derived from four observational studies, obtaining disease state assignment for each study visit. Using large-scale screening, we estimated Cohen's effect sizes to rank the discriminative power of 2,472 clinical measures for separating observations in disease state pairs. Individual trajectories through IHDPM states were examined. Discriminative analyses were limited to individuals with observations in both states of the pairs compared (N = 3,790). Results: Discriminative clinical measures were heterogeneous across the HD life course. UHDRS items were frequently identified as the best state pair discriminators, with UHDRS Motor items - most notably TMS - showing the highest discriminatory power between the early-disease states and early post-transition period states. UHDRS functional items emerged as strong discriminators from the transition period and on. Cognitive assessments showed good discriminative power between all state pairs examined, excepting state 1 vs. 2. Several non-UHDRS assessments were also flagged as excellent state discriminators for specific disease phases (e.g., SF-12). For certain state pairs, single assessment items other than total/summary scores were highlighted as having excellent discriminative power. Conclusion: By providing ranked quantitative scores indicating discriminatory ability of thousands of clinical measures between specific pairs of IHDPM states, our results will aid clinical trial designers select the most effective outcome measures tailored to their study cohort. Our observations may also assist in the development of end points targeting specific phases in the disease life course, through providing specific conceptual foci.

Speak and you shall predict: speech at initial cocaine abstinence as a biomarker of long-term drug use behavior.

Importance: Valid biomarkers that can predict longitudinal clinical outcomes at low cost are a holy grail in psychiatric research, promising to ultimately be used to optimize and tailor intervention and prevention efforts. Objective: To determine if baseline linguistic markers in natural speech, as compared to non-speech clinical and demographic measures, can predict drug use severity measures at future sessions in initially abstinent individuals with cocaine use disorder (iCUD). Design: A longitudinal cohort study (August 2017 - March 2020), where baseline measures were used to predict outcomes collected at three-month intervals for up to one year of follow-up. Participants: Eighty-eight initially abstinent iCUD were studied at baseline; 57 (46 male, age 50.7+/-7.9 years) came back for at least another session. Main Outcomes and Measures: Outcomes were self-reported symptoms of withdrawal, craving, abstinence duration and frequency of cocaine use in the past 90 days at each study session. The predictors were derived from 5-min recordings of vocal descriptions of the positive consequences of abstinence and the negative consequences of using cocaine; the baseline cocaine and other common drug use measures, demographic and neuropsychological variables were used for comparison. Results: Models using the non-speech variables showed the best predictive performance at three(r>0.45, P<2×10-3) and six months follow-up (r>0.37, P<3×10-2). At 12 months, the natural language processing-based model showed significant correlations with withdrawal (r=0.43, P=3×10-2), craving (r=0.72, P=5×10-5), days of abstinence (r=0.76, P=1×10-5), and cocaine use in the past 90 days (r=0.61, P=2×10-3), significantly outperforming the other models for abstinence prediction. Conclusions and Relevance: At short time intervals, maximal predictive power was obtained with models that used baseline drug use (in addition to demographic and neuropsychological) measures, potentially reflecting a slow rate of change in these measures, which could be estimated by linear functions. In contrast, short speech samples predicted longer-term changes in drug use, implying deeper penetrance by potentially capturing non-linear dynamics over longer intervals. Results suggest that, compared to the common outcome measures used in clinical trials, speech-based measures could be leveraged as better predictors of longitudinal drug use outcomes in initially abstinent iCUD, as potentially generalizable to other substance use disorders and related comorbidity.

Informing clinical assessment by contextualizing post-hoc explanations of risk prediction models in type-2 diabetes.

Medical experts may use Artificial Intelligence (AI) systems with greater trust if these are supported by 'contextual explanations' that let the practitioner connect system inferences to their context of use. However, their importance in improving model usage and understanding has not been extensively studied. Hence, we consider a comorbidity risk prediction scenario and focus on contexts regarding the patients' clinical state, AI predictions about their risk of complications, and algorithmic explanations supporting the predictions. We explore how relevant information for such dimensions can be extracted from Medical guidelines to answer typical questions from clinical practitioners. We identify this as a question answering (QA) task and employ several state-of-the-art Large Language Models (LLM) to present contexts around risk prediction model inferences and evaluate their acceptability. Finally, we study the benefits of contextual explanations by building an end-to-end AI pipeline including data cohorting, AI risk modeling, post-hoc model explanations, and prototyped a visual dashboard to present the combined insights from different context dimensions and data sources, while predicting and identifying the drivers of risk of Chronic Kidney Disease (CKD) - a common type-2 diabetes (T2DM) comorbidity. All of these steps were performed in deep engagement with medical experts, including a final evaluation of the dashboard results by an expert medical panel. We show that LLMs, in particular BERT and SciBERT, can be readily deployed to extract some relevant explanations to support clinical usage. To understand the value-add of the contextual explanations, the expert panel evaluated these regarding actionable insights in the relevant clinical setting. Overall, our paper is one of the first end-to-end analyses identifying the feasibility and benefits of contextual explanations in a real-world clinical use case. Our findings can help improve clinicians' usage of AI models.

Linguistic markers predict onset of Alzheimer's disease.

BACKGROUND: The aim of this study is to use classification methods to predict future onset of Alzheimer's disease in cognitively normal subjects through automated linguistic analysis. METHODS: To study linguistic performance as an early biomarker of AD, we performed predictive modeling of future diagnosis of AD from a cognitively normal baseline of Framingham Heart Study participants. The linguistic variables were derived from written responses to the cookie-theft picture-description task. We compared the predictive performance of linguistic variables with clinical and neuropsychological variables. The study included 703 samples from 270 participants out of which a dataset consisting of a single sample from 80 participants was held out for testing. Half of the participants in the test set developed AD symptoms before 85 years old, while the other half did not. All samples in the test set were collected during the cognitively normal period (before MCI). The mean time to diagnosis of mild AD was 7.59 years. FINDINGS: Significant predictive power was obtained, with AUC of 0.74 and accuracy of 0.70 when using linguistic variables. The linguistic variables most relevant for predicting onset of AD have been identified in the literature as associated with cognitive decline in dementia. INTERPRETATION: The results suggest that language performance in naturalistic probes expose subtle early signs of progression to AD in advance of clinical diagnosis of impairment. FUNDING: Pfizer, Inc. provided funding to obtain data from the Framingham Heart Study Consortium, and to support the involvement of IBM Research in the initial phase of the study. The data used in this study was supported by Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195), and by grants from the National Institute on Aging grants (R01-AG016495, R01-AG008122) and the National Institute of Neurological Disorders and Stroke (R01-NS017950).

Identifying signals associated with psychiatric illness utilizing language and images posted to Facebook.

Prior research has identified associations between social media activity and psychiatric diagnoses; however, diagnoses are rarely clinically confirmed. Toward the goal of applying novel approaches to improve outcomes, research using real patient data is necessary. We collected 3,404,959 Facebook messages and 142,390 images across 223 participants (mean age = 23.7; 41.7% male) with schizophrenia spectrum disorders (SSD), mood disorders (MD), and healthy volunteers (HV). We analyzed features uploaded up to 18 months before the first hospitalization using machine learning and built classifiers that distinguished SSD and MD from HV, and SSD from MD. Classification achieved AUC of 0.77 (HV vs. MD), 0.76 (HV vs. SSD), and 0.72 (SSD vs. MD). SSD used more (P < 0.01) perception words (hear, see, feel) than MD or HV. SSD and MD used more (P < 0.01) swear words compared to HV. SSD were more likely to express negative emotions compared to HV (P < 0.01). MD used more words related to biological processes (blood/pain) compared to HV (P < 0.01). The height and width of photos posted by SSD and MD were smaller (P < 0.01) than HV. MD photos contained more blues and less yellows (P < 0.01). Closer to hospitalization, use of punctuation increased (SSD vs HV), use of negative emotion words increased (MD vs. HV), and use of swear words increased (P < 0.01) for SSD and MD compared to HV. Machine-learning algorithms are capable of differentiating SSD and MD using Facebook activity alone over a year in advance of hospitalization. Integrating Facebook data with clinical information could one day serve to inform clinical decision-making.

Analyzing acoustic and prosodic fluctuations in free speech to predict psychosis onset in high-risk youths.

The diagnosis and treatment of psychiatric disorders depends on the analysis of behavior through language by a clinical specialist. This analysis is subjective in nature and could benefit from automated, objective acoustic and linguistic processing methods. This integrated approach would convey a richer representation of patient speech, particularly for expression of emotion. In this work, we explore the potential of acoustic and prosodic metrics to infer clinical variables and predict psychosis, a condition which produces measurable derailment and tangentiality in patient language. To that purpose, we analyzed the recordings of 32 young patients at high risk of developing clinical psychosis. The subjects were evaluated using the Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms (SIPS/SOPS) criteria. To analyze the recordings, we examined the variation of different acoustic and prosodic metrics across time. This preliminary analysis shows that these features can infer negative symptom severity ratings (i.e., SIPS-Btotal), obtaining a Pearson correlation of 0.77 for all the subjects after cross-validated evaluation. In addition, these features can predict development of psychosis with high accuracy above 90%, outperforming classification using clinical variables only. This improved predictive power ultimately can help provide early treatment and improve quality of life for those at risk for developing psychosis.

From discourse to pathology: Automatic identification of Parkinson's disease patients via morphological measures across three languages.

Embodied cognition research on Parkinson's disease (PD) points to disruptions of frontostriatal language functions as sensitive targets for clinical assessment. However, no existing approach has been tested for crosslinguistic validity, let alone by combining naturalistic tasks with machine-learning tools. To address these issues, we conducted the first classifier-based examination of morphological processing (a core frontostriatal function) in spontaneous monologues from PD patients across three typologically different languages. The study comprised 330 participants, encompassing speakers of Spanish (61 patients, 57 matched controls), German (88 patients, 88 matched controls), and Czech (20 patients, 16 matched controls). All subjects described the activities they perform during a regular day, and their monologues were automatically coded via morphological tagging, a computerized method that labels each word with a part-of-speech tag (e.g., noun, verb) and specific morphological tags (e.g., person, gender, number, tense). The ensuing data were subjected to machine-learning analyses to assess whether differential morphological patterns could classify between patients and controls and reflect the former's degree of motor impairment. Results showed robust classification rates, with over 80% of patients being discriminated from controls in each language separately. Moreover, the most discriminative morphological features were associated with the patients' motor compromise (as indicated by Pearson r correlations between predicted and collected motor impairment scores that ranged from moderate to moderate-to-strong across languages). Taken together, our results suggest that morphological patterning, an embodied frontostriatal domain, may be distinctively affected in PD across languages and even under ecological testing conditions.

Analyzing progression of motor and speech impairment in ALS.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease which causes death of neurons controlling voluntary muscles. It is currently assessed with subjective clinical measurements, but it would benefit from alternative surrogate biomarkers that can better estimate disease progression. This work analyzes speech and fine motor coordination of subjects recruited by the Answer ALS foundation using data from a mobile app. In addition, clinical variables such as speech, writing and total ALSFRS-R scores are also acquired along with forced and slow vital capacity. Cross-sectional and longitudinal analyses were performed using speech and fine motor features. Results show that both types of features are useful to infer clinical variables especially for males (R2=0.79 for ALSFRS-R total score), but their initial values are not helpful to predict speech and motor decline. However, we found that longitudinal progression for bulbar and spinal ALS onset are different and they can be identified with high accuracy by the extracted features.