Automatic classification of AD pathology in FTD phenotypes using natural speech.

INTRODUCTION: Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD). METHODS: We trained automatic classifiers with 99 speech features from 1 minute speech samples of 179 participants (ADNC = 36, FTLD = 60, healthy controls [HC] = 89). Patients' pathology was assigned based on autopsy or cerebrospinal fluid analytes. Structural network-based magnetic resonance imaging analyses identified anatomical correlates of distinct speech features. RESULTS: Our classifier showed 0.88 ± $ \pm $ 0.03 area under the curve (AUC) for ADNC versus FTLD and 0.93 ± $ \pm $ 0.04 AUC for patients versus HC. Noun frequency and pause rate correlated with gray matter volume loss in the limbic and salience networks, respectively. DISCUSSION: Brief naturalistic speech samples can be used for screening FTD patients for underlying ADNC in vivo. This work supports the future development of digital assessment tools for FTD. HIGHLIGHTS: We trained machine learning classifiers for frontotemporal dementia patients using natural speech. We grouped participants by neuropathological diagnosis (autopsy) or cerebrospinal fluid biomarkers. Classifiers well distinguished underlying pathology (Alzheimer's disease vs. frontotemporal lobar degeneration) in patients. We identified important features through an explainable artificial intelligence approach. This work lays the groundwork for a speech-based neuropathology screening tool.

Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated With Frontotemporal Degeneration.

BACKGROUND AND OBJECTIVES: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic. METHODS: In this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier" or "noncarrier" was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally. RESULTS: A total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (ß = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (ß = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (ß = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease. DISCUSSION: Using automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.

Automated Measures of Syntactic Complexity in Natural Speech Production: Older and Younger Adults as a Case Study.

PURPOSE: Multiple methods have been suggested for quantifying syntactic complexity in speech. We compared eight automated syntactic complexity metrics to determine which best captured verified syntactic differences between old and young adults. METHOD: We used natural speech samples produced in a picture description task by younger (n = 76, ages 18-22 years) and older (n = 36, ages 53-89 years) healthy participants, manually transcribed and segmented into sentences. We manually verified that older participants produced fewer complex structures. We developed a metric of syntactic complexity using automatically extracted syntactic structures as features in a multidimensional metric. We compared our metric to seven other metrics: Yngve score, Frazier score, Frazier-Roark score, developmental level, syntactic frequency, mean dependency distance, and sentence length. We examined the success of each metric in identifying the age group using logistic regression models. We repeated the analysis with automatic transcription and segmentation using an automatic speech recognition (ASR) system. RESULTS: Our multidimensional metric was successful in predicting age group (area under the curve [AUC] = 0.87), and it performed better than the other metrics. High AUCs were also achieved by the Yngve score (0.84) and sentence length (0.84). However, in a fully automated pipeline with ASR, the performance of these two metrics dropped (to 0.73 and 0.46, respectively), while the performance of the multidimensional metric remained relatively high (0.81). CONCLUSIONS: Syntactic complexity in spontaneous speech can be quantified by directly assessing syntactic structures and considering them in a multivariable manner. It can be derived automatically, saving considerable time and effort compared to manually analyzing large-scale corpora, while maintaining high face validity and robustness. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24964179.

Prosodic characteristics of prepausal words produced by patients with neurodegenerative disease.

Prosody of patients with neurodegenerative disease is often impaired. We investigated changes to two prosodic cues in patients: the pitch contour and the duration of prepausal words. We analyzed recordings of picture descriptions produced by patients with neurodegenerative conditions that included either cognitive (n=223), motor (n=68), or mixed cognitive and motor impairments (n=109), and by healthy controls (n=28; HC). A speech activity detector identified pauses. Words were aligned to the acoustic signal; pitch values were normalized in scale and duration. Analyses of pitch showed that the ending (90th-100th percentile) of prepausal words had a lower pitch in the mixed and motor groups than the cognitive group and HC. The pitch contour from the midpoint of words to the end showed a steep rising slope for HC, but patients showed a gentle rising or flat slope. This suggests that HC signaled the continuation of their description after the pause with rising contour; patients either failed to keep describing the picture due to cognitive impairment or could not raise pitch due to motor impairments. Prepausal words showed longer duration relative to non-prepausal words with no significant differences between the groups. This suggests that prepausal lengthening is preserved in patients.

Negative sentences exhibit a sustained effect in delayed verification tasks.

Negated sentences are known to be more cognitively taxing than positive ones (i.e., polarity effect). We present evidence that two factors contribute to the polarity effect in verification tasks: processing the sentence and verifying its truth value. To quantify the relative contribution of each, we used a delayed verification task. The results show that even when participants are given a considerable amount of time for processing the sentence prior to verification, the polarity effect is not entirely eliminated. We suggest that this sustained effect stems from a retained negation-containing representation in working memory. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Attention to speech: mapping distributed and selective attention systems.

When faced with situations where many people talk at once, individuals can employ different listening strategies to deal with the cacophony of speech sounds and to achieve different goals. In this fMRI study, we investigated how the pattern of neural activity is affected by the type of attention applied to speech in a simulated "cocktail party." Specifically, we compared brain activation patterns when listeners "attended selectively" to only one speaker and ignored all others, versus when they "distributed their attention" and followed several concurrent speakers. Conjunction analysis revealed a highly overlapping network of regions activated for both types of attention, including auditory association cortex (bilateral STG/STS) and frontoparietal regions related to speech processing and attention (bilateral IFG/insula, right MFG, left IPS). Activity within nodes of this network, though, was modulated by the type of attention required as well as the number of competing speakers. Auditory and speech-processing regions exhibited higher activity during distributed attention, whereas frontoparietal regions were activated more strongly during selective attention. These results suggest a common "attention to speech" network, which provides the computational infrastructure to deal effectively with multi-speaker input, but with sufficient flexibility to implement different prioritization strategies and to adapt to different listener goals.

Negative polarity in quantifiers evokes greater activation in language-related regions compared to negative polarity in adjectives.

The processing of sentences with negative quantifiers (e.g., few) is more costly than of sentences that contain their positive counterparts (e.g., many). While this polarity effect is robust and reliably replicable, its neurological bases are not well understood. In this study, we use functional magnetic resonance imaging (fMRI) paradigm for 30 participants to assess the polarity effect in sentences with polar quantifiers, and compare it with the polarity effect of polar adjectives. Both in quantifiers and in adjectives, the polarity effect manifests in the anterior insula bilaterally. The polarity effect in quantifiers, however, shows greater activation in the left hemisphere than it does for adjectives. In particular, left inferior frontal gyrus (IFG) and left superior temporal sulcus (STS) show increased activation for polarity in quantifiers than in adjectives, which is the evidence for the specific involvement of the language network in this type of polarity processing. Using the polarity effect in adjectives as a control, we provide further evidence for the linguistic complexity that negative quantifiers implicate on processing.

Paying attention to speech: The role of working memory capacity and professional experience.

Managing attention in multispeaker environments is a challenging feat that is critical for human performance. However, why some people are better than others in allocating attention appropriately remains highly unknown. Here, we investigated the contribution of two factors-working memory capacity (WMC) and professional experience-to performance on two different types of attention task: selective attention to one speaker and distributed attention among multiple concurrent speakers. We compared performance across three groups: individuals with low (n = 20) and high (n = 25) WMC, and aircraft pilots (n = 24), whose profession poses extremely high demands for both selective and distributed attention to speech. Results suggests that selective attention is highly effective, with good performance maintained under increasingly adverse conditions, whereas performance decreases substantially with the requirement to distribute attention among a larger number of speakers. Importantly, both types of attention benefit from higher WMC, suggesting reliance on some common capacity-limited resources. However, only selective attention was further improved in the pilots, pointing to its flexible and trainable nature, whereas distributed attention seems to suffer from more fixed and severe processing bottlenecks.

Logical negation mapped onto the brain.

High-level cognitive capacities that serve communication, reasoning, and calculation are essential for finding our way in the world. But whether and to what extent these complex behaviors share the same neuronal substrate are still unresolved questions. The present study separated the aspects of logic from language and numerosity-mental faculties whose distinctness has been debated for centuries-and identified a new cytoarchitectonic area as correlate for an operation involving logical negation. A novel experimental paradigm that was implemented here in an RT/fMRI study showed a single cluster of activity that pertains to logical negation. It was distinct from clusters that were activated by numerical comparison and from the traditional language regions. The localization of this cluster was described by a newly identified cytoarchitectonic area in the left anterior insula, ventro-medial to Broca's region. We provide evidence for the congruence between the histologically and functionally defined regions on multiple measures. Its position in the left anterior insula suggests that it functions as a mediator between language and reasoning areas.

The processing of polar quantifiers, and numerosity perception.

We investigated the course of language processing in the context of a verification task that required numerical estimation and comparison. Participants listened to sentences with complex quantifiers that contrasted in Polarity, a logical property (e.g., more-than-half, less-than-half), and then performed speeded verification on visual scenarios that displayed a proportion between 2 discrete quantities. We varied systematically not only the sentences, but also the visual materials, in order to study their effect on the verification process. Next, we used the same visual scenarios with analogous non-verbal probes that featured arithmetical inequality symbols (<, >). This manipulation enabled us to measure not only Polarity effects, but also, to compare the effect of different probe types (linguistic, non-linguistic) on processing. Like many previous studies, our results demonstrate that perceptual difficulty affects error rate and reaction time in keeping with Weber's Law. Interestingly, these performance parameters are also affected by the Polarity of the quantifiers used, despite the fact that sentences had the exact same meaning, sentence structure, number of words, syllables, and temporal structure. Moreover, an analogous contrast between the non-linguistic probes (<, >) had no effect on performance. Finally, we observed no interaction between performance parameters governed by Weber's Law and those affected by Polarity. We consider 4 possible accounts of the results (syntactic, semantic, pragmatic, frequency-based), and discuss their relative merit.