Atypical cortical hierarchy in Aß-positive older adults and its reflection in spontaneous speech.

Abnormal deposition of Aß amyloid is an early neuropathological marker of Alzheimer's disease (AD), arising long ahead of clinical symptoms. Non-invasive measures of associated early neurofunctional changes, together with easily accessible behavioral readouts of these changes, could be of great clinical benefit. We pursued this aim by investigating large-scale cortical gradients of functional connectivity with functional MRI, which capture the hierarchical integration of cortical functions, together with acoustic-prosodic features from spontaneous speech, in cognitively unimpaired older adults with and without Aß positivity (total N = 188). We predicted distortions of the cortical hierarchy associated with prosodic changes in the Aß + group. Results confirmed substantially altered cortical hierarchies and less variability in these in the Aß + group, together with an increase in quantitative prosodic measures, which correlated with gradient variability as well as digit span test scores. Overall, these findings confirm that long before the clinical stage and objective cognitive impairment, increased risk of cognitive decline as indexed by Aß accumulation is marked by neurofunctional changes in the cortical hierarchy, which are related to automatically extractable speech patterns and alterations in working memory functions.

Navigating the semantic space: Unraveling the structure of meaning in psychosis using different computational language models.

Speech in psychosis has long been ascribed as involving 'loosening of associations'. We pursued the aim to elucidate its underlying cognitive mechanisms by analysing picture descriptions from 94 subjects (29 healthy controls, 18 participants at clinical high risk, 29 with first-episode psychosis, and 18 with chronic schizophrenia), using five language models with different computational architectures: FastText, which represents meaning non-contextually/statically; BERT, which represents contextual meaning sensitive to grammar and context; Infersent and SBERT, which provide sentential representations; and CLIP, which evaluates speech relative to a visual stimulus. These models were used to quantify semantic distances crossed between successive tokens/sentences, and semantic perplexity indicating unexpectedness in continuations. Results showed that, among patients, semantic similarity increased when measured with FastText, Infersent, and SBERT, while it decreased with CLIP and BERT. Higher perplexity was observed in first-episode psychosis. Static semantic measures were associated with clinically measured impoverishment of thought and referential semantic measures with disorganization. These patterns indicate a shrinking conceptual semantic space as represented by static language models, which co-occurs with a widening in the referential semantic space as represented by contextual models. This duality underlines the need to separate these two forms of meaning for understanding mechanisms involved in semantic change in psychosis.

The 'L-factor': Language as a transdiagnostic dimension in psychopathology.

Thoughts and moods constituting our mental life incessantly change. When the steady flow of this dynamics diverges in clinical directions, the possible pathways involved are captured through discrete diagnostic labels. Yet a single vulnerable neurocognitive system may be causally involved in psychopathological deviations transdiagnostically. We argue that language viewed as integrating cortical functions is the best current candidate, whose forms of breakdown along its different dimensions are then manifest as symptoms - from prosodic abnormalities and rumination in depression to distortions of speech perception in verbal hallucinations, distortions of meaning and content in delusions, or disorganized speech in formal thought disorder. Spontaneous connected speech provides continuous objective readouts generating a highly accessible bio-behavioral marker with the potential of revolutionizing neuropsychological measurement. This argument turns language into a transdiagnostic 'L-factor' providing an analytical and mechanistic substrate for previously proposed latent general factors of psychopathology ('p-factor') and cognitive functioning ('c-factor'). Together with immense practical opportunities afforded by rapidly advancing natural language processing (NLP) technologies and abundantly available data, this suggests a new era of translational clinical psychiatry, in which both psychopathology and language may be rethought together.

Episodic Thinking in Alzheimer's Disease Through the Lens of Language: Linguistic Analysis and Transformer-Based Classification.

PURPOSE: Episodic memory decline is a hallmark of Alzheimer's disease (AD) and linked to deficits in episodic thinking directed to the future. We addressed the question whether a deficit in episodic thinking can be picked up directly from connected speech and its detection can be automatized. METHOD: We linguistically classified 2,809 utterances (including embedded clauses in the utterances) from picture descriptions from 70 healthy older controls, 82 people with mild probable AD (pAD), and 46 people with moderate pAD for whether they were episodic, nonepisodic, or "other" (e.g., off-task). Generalized linear regression models were used to investigate how ratios of these categories change in AD, controlling for age, gender, and education. Finally, we applied deep learning technique to explore the feasibility of automating the episodicity analysis. RESULTS: Decline in episodicity significantly distinguished controls from both mild pAD and moderate pAD. Correlation analysis suggested this decline not to be an effect of age, gender, and education but of cognitive ability. The decline was not compensated by an increase of nonepisodic utterances but mainly of off-task expressions. A transformer-based classifier to explore the possibility of automatizing the classification of episodicity achieved a macro F1 score of 0.913 in the ternary classification. CONCLUSION: These results show that a loss of episodicity is an early effect in AD that is manifested in spontaneous speech and can be reliably measured by both humans and machines.

Functional dysregulation of the auditory cortex in bilateral perisylvian polymicrogyria: Multiparametric case analysis of the absent speech phenotype.

The absence of speech is a clinical phenotype seen across neurodevelopmental syndromes, offering insights for neural language models. We present a case of bilateral perisylvian polymicrogyria (BPP) and complete absence of speech with considerable language comprehension and production difficulties. We extensively characterized the auditory speech perception and production circuitry by employing a multimodal neuroimaging approach. Results showed extensive cortical thickening in motor and auditory-language regions. The auditory cortex lacked sensitivity to speech stimuli despite relatively preserved thalamic projections yet had no intrinsic functional organization. Subcortical structures implicated in early stages of processing exhibited heightened sensitivity to speech. The arcuate fasciculus, a suggested marker of language in BPP, showed similar volume and integrity to a healthy control. The frontal aslant tract, linked to oromotor function, was partially reconstructed. These findings highlight the importance of assessing the auditory cortex beyond speech production structures to understand absent speech in BPP. Despite profound cortical alterations, the intrinsic motor network and motor-speech pathways remained largely intact. This case underscores the need for comprehensive phenotyping using multiple MRI modalities to uncover causes of severe disruption in language development.

Harnessing acoustic speech parameters to decipher amyloid status in individuals with mild cognitive impairment.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of mild cognitive impairment (MCI) to enable early interventions. Among the neuropathological events associated with the onset of the disease is the accumulation of amyloid protein in the brain, which correlates with decreased levels of Aß42 peptide in the cerebrospinal fluid (CSF). Consequently, the development of non-invasive, low-cost, and easy-to-administer proxies for detecting Aß42 positivity in CSF becomes particularly valuable. A promising approach to achieve this is spontaneous speech analysis, which combined with machine learning (ML) techniques, has proven highly useful in AD. In this study, we examined the relationship between amyloid status in CSF and acoustic features derived from the description of the Cookie Theft picture in MCI patients from a memory clinic. The cohort consisted of fifty-two patients with MCI (mean age 73 years, 65% female, and 57% positive amyloid status). Eighty-eight acoustic parameters were extracted from voice recordings using the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS), and several ML models were used to classify the amyloid status. Furthermore, interpretability techniques were employed to examine the influence of input variables on the determination of amyloid-positive status. The best model, based on acoustic variables, achieved an accuracy of 75% with an area under the curve (AUC) of 0.79 in the prediction of amyloid status evaluated by bootstrapping and Leave-One-Out Cross Validation (LOOCV), outperforming conventional neuropsychological tests (AUC = 0.66). Our results showed that the automated analysis of voice recordings derived from spontaneous speech tests offers valuable insights into AD biomarkers during the preclinical stages. These findings introduce novel possibilities for the use of digital biomarkers to identify subjects at high risk of developing AD.

Automated Classification of Cognitive Decline and Probable Alzheimer's Dementia Across Multiple Speech and Language Domains.

BACKGROUND: Decline in language has emerged as a new potential biomarker for the early detection of Alzheimer's disease (AD). It remains unclear how sensitive language measures are across different tasks, language domains, and languages, and to what extent changes can be reliably detected in early stages such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHOD: Using a scene construction task for speech elicitation in a new Spanish/Catalan speaking cohort (N = 119), we automatically extracted features across seven domains, three acoustic (spectral, cepstral, and voice quality), one prosodic, and three from text (morpholexical, semantic, and syntactic). They were forwarded to a random forest classifier to evaluate the discriminability of participants with probable AD dementia, amnestic and nonamnestic MCI, SCD, and cognitively healthy controls. Repeated-measures analyses of variance and paired-samples Wilcoxon signed-ranks test were used to assess whether and how performance differs significantly across groups and linguistic domains. RESULTS: The performance scores of the machine learning classifier were generally satisfactorily high, with the highest scores over .9. Model performance was significantly different for linguistic domains (p < .001), and speech versus text (p = .043), with speech features outperforming textual features, and voice quality performing best. High diagnostic classification accuracies were seen even within both cognitively healthy (controls vs. SCD) and MCI (amnestic and nonamnestic) groups. CONCLUSION: Speech-based machine learning is powerful in detecting cognitive decline and probable AD dementia across a range of different feature domains, though important differences exist between these domains as well. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23699733.

Linguistic markers of psychosis in Mandarin Chinese: Relations to theory of mind.

Disorganized and impoverished language is a key feature of schizophrenia (Sz), but whether and which linguistic changes previously observed in Indo-European languages generalize to other languages remains unclear. Targeting Mandarin Chinese, we aimed to profile aspects of grammatical complexity that we hypothesized would be reduced in schizophrenia in a task of verbalizing social events. 51 individuals with Sz and 39 controls participated in the animated triangles task, a standardized measure of theory of mind (ToM), in which participants describe triangles moving in either a random or an 'intentional' condition. Results revealed that clauses embedded as arguments in other clauses were reduced in Sz, and that both groups produced such clauses and grammatical aspect more frequently in the intentional condition. ToM scores specifically correlated with production of embedded argument clauses. These results document grammatical impoverishment in Sz in Chinese across several structural domains, which in some of its specific aspects relate to mentalizing performance.

Linguistic markers of autism spectrum conditions in narratives: A comprehensive analysis.

Background & Aims: Narratives are regularly elicited as part of standardized assessments for autism spectrum conditions (ASC) such as the ADOS, but have rarely been utilized as linguistic data in their own right. We here aimed for a specific and comprehensive quantitative linguistic profile of such narratives across nominal, verbal, and clausal domains of grammatical organization, and error patterns. Methods: We manually transcribed and annotated narratives elicited from the ADOS from a sample of bilingual autistic Spanish-Catalan children (n = 18), matched with typically developing controls (n = 18) on vocabulary-based verbal IQ. Results: Results revealed fewer relative clauses and more frequent errors in referential specificity and non-relational content-word choice in ASC. Frequent error types are also discussed qualitatively. Conclusions & Implications: These findings, based on more finegrained linguistically defined variables, help to disentangle previous inconsistencies in the literature, and to better situate language changes in the spectrum of neurocognitive changes in this population.

Natural Language Processing Markers for Psychosis and Other Psychiatric Disorders: Emerging Themes and Research Agenda From a Cross-Linguistic Workshop.

This workshop summary on natural language processing (NLP) markers for psychosis and other psychiatric disorders presents some of the clinical and research issues that NLP markers might address and some of the activities needed to move in that direction. We propose that the optimal development of NLP markers would occur in the context of research efforts to map out the underlying mechanisms of psychosis and other disorders. In this workshop, we identified some of the challenges to be addressed in developing and implementing NLP markers-based Clinical Decision Support Systems (CDSSs) in psychiatric practice, especially with respect to psychosis. Of note, a CDSS is meant to enhance decision-making by clinicians by providing additional relevant information primarily through software (although CDSSs are not without risks). In psychiatry, a field that relies on subjective clinical ratings that condense rich temporal behavioral information, the inclusion of computational quantitative NLP markers can plausibly lead to operationalized decision models in place of idiosyncratic ones, although ethical issues must always be paramount.

Coreference Delays in Psychotic Discourse: Widening the Temporal Window.

BACKGROUND AND HYPOTHESIS: Any form of coherent discourse depends on saying different things about the same entities at different times. Such recurrent references to the same entity need to predictably happen within certain temporal windows. We hypothesized that a failure of control over reference in speakers with schizophrenia (Sz) would become manifest through dynamic temporal measures. STUDY DESIGN: Conversational speech with a mean of 909.2 words (SD: 178.4) from 20 Chilean Spanish speakers with chronic Sz, 20 speakers at clinical high risk (CHR), and 20 controls were collected. Using directed speech graphs with referential noun phrases (NPs) as nodes, we studied deviances in the topology and temporal distribution of such NPs and of the entities they denote over narrative time. STUDY RESULTS: The Sz group had a larger density of NPs (number of NPs divided by total words) relative to both controls and CHR. This related to topological measures of distance between recurrent entities, which revealed that the Sz group produced more recurrences, as well as greater topological distances between them, relative to controls. A logistic regression using five topological measures showed that Sz and controls can be distinguished with 84.2% accuracy. CONCLUSIONS: This pattern indicates a widening of the temporal window in which entities are maintained in discourse and co-referenced in it. It substantiates and extends earlier evidence for deficits in the cognitive control over linguistic reference in psychotic discourse and informs both neurocognitive models of language in Sz and machine learning-based linguistic classifiers of psychotic speech.

Temporal Overlap Between Gestures and Speech in Poststroke Aphasia: Is There a Compensatory Effect?

PURPOSE: If language production is impaired, will gestures compensate? Evidence in favor of this prediction has often been argued to come from aphasia, but it remains contested. Here, we tested whether thought content not present in speech due to language impairment is manifested in gestures, in 20 people with dysfluent (Broca's) aphasia, 20 people with fluent (Wernicke's) aphasia, and 20 matched neurotypical controls. METHOD: A new annotation scheme was created distinguishing types of gestures and whether they co-occurred with fluent or dysfluent/absent speech and were temporally aligned in content with coproduced speech. RESULTS: Across both aphasia types, noncontent (beat) gestures, which by their nature cannot compensate for lost speech content, constituted the greatest proportion of all types of gestures produced. Content (i.e., descriptive, referential, and metaphorical) gestures were largely coproduced with fluent rather than dysfluent speech and tended to be aligned with the content conveyed in speech. They also did not differ in quantity depending on whether the dysfluencies were eventually resolved or not. Neither aphasia severity nor comprehension ability had an impact on the total amount of content gesture produced in people with aphasia, which was instead positively correlated with speech fluency. CONCLUSIONS: Together, these results suggest that gestures are unlikely to have a role in compensating for linguistic deficits and to serve as a representational system conveying thought content independent of language. Surprisingly, aphasia rather is a model of how gesture and language are inherently integrated and aligned: Even when language is impaired, it remains the essential provider of content.

Grammar in 'agrammatical' aphasia: What's intact?

BACKGROUND: Aphasia following cerebro-vascular accidents has been a primary source of insight for models of language in the brain. However, deviant language patterns in aphasia may reflect processing limitations and cognitive impairment more than language impairment per se. AIMS: We sought to obtain new evidence from spontaneous speech in Broca's aphasia (BA) for the intactness of grammatical knowledge, operationalized as the preservation of the basic hierarchical structure of syntactic projections. METHODS & PROCEDURES: Speech obtained with the AphasiaBank protocol from 20 people with BA, which were independently rated as also being agrammatic, was analyzed and compared to 20 matched non-brain-damaged controls. We quantified (i) marking of Aspect, Tense, and Modality (A-T-M), which are located at specific (high) layers of the syntactic hierarchy and ordered in relation to one another ([M…[T…[A…]]]); (ii) hierarchies of clausal units ([C…[C]]); (iii) discourse markers embedding clauses, located at the highest layer of the hierarchy; and (iv) attachment of adjuncts at different heights of a given hierarchical syntactic structure. Supplementary evidence was obtained from a typology of errors and from pauses subcategorized according to their hierarchical syntactic position. OUTCOMES & RESULTS: Groups did not quantitatively differ on rates of either Aspect or Modality but underproduced T and embedded clauses. Evidence for compensatory effects was seen in both of the latter two cases. While all adjunct types were underproduced in BA, and pauses overproduced, both showed the same relative proportions within both groups. Errors were largely restricted to omissions, of a kind that would also be expected in condensed neurotypical speech. CONCLUSIONS: Overall, these patterns support the hypothesis of intactness of grammatical knowledge in BA clinically rated as agrammatic, questioning it as a disease model of language impairment.

Brain correlates of speech perception in schizophrenia patients with and without auditory hallucinations.

The experience of auditory verbal hallucinations (AVH, "hearing voices") in schizophrenia has been found to be associated with reduced auditory cortex activation during perception of real auditory stimuli like tones and speech. We re-examined this finding using 46 patients with schizophrenia (23 with frequent AVH and 23 hallucination-free), who underwent fMRI scanning while they heard words, sentences and reversed speech. Twenty-five matched healthy controls were also examined. Perception of words, sentences and reversed speech all elicited activation of the bilateral superior temporal cortex, the inferior and lateral prefrontal cortex, the inferior parietal cortex and the supplementary motor area in the patients and the healthy controls. During the sentence and reversed speech conditions, the schizophrenia patients as a group showed reduced activation in the left primary auditory cortex (Heschl's gyrus) relative to the healthy controls. No differences were found between the patients with and without hallucinations in any condition. This study therefore fails to support previous findings that experience of AVH attenuates speech-perception-related brain activations in the auditory cortex. At the same time, it suggests that schizophrenia patients, regardless of presence of AVH, show reduced activation in the primary auditory cortex during speech perception, a finding which could reflect an early information processing deficit in the disorder.

Language level predicts perceptual categorization of complex reversible events in children.

Language plays a well-documented role in perceptual object categorization, but little is known about its role in the categorization of complex events. We explored this here with a perspective from age or developmentally appropriate language capacities in neurotypical children between the ages of two and four years (N = 21), and from delayed language development in a clinical group of children (N = 20), whose verbal mental ages (VMA) often fell far below their chronological ages (CAs). All participants watched two demonstrations of a series of transitive events (e.g. tiger jumps over a girl). The toy agents were then moved out of sight, and participants had to act out the same event type, based on a different tiger and girl that were selected among two distractors. We aimed to determine how mastery of this task relates to CA in the neurotypical group, and whether task performance in the clinical group was predicted by VMA and a standardized measure of grammatical comprehension. Results from a series of logistic mixed-effect regression models showed that neurotypical children start to perform correctly on this task with a chance of around 50% during their third year of CA but reach ceiling performance only during their fourth. A similar pattern emerged for VMA in the clinical group, despite a wide range of CAs and diagnoses. In addition, grammatical comprehension predicted performance. These patterns suggest that language competence plays a role in the perceptual categorization and encoding of complex reversible events.

Processing of linguistic deixis in people with schizophrenia, with and without auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous perception of speech. Anomalies of processing external speech stimuli have also been reported in people with AVH, but it is unexplored which specific dimensions of language are processed differently. Using a speech perception task (passive listening), we here targeted the processing of deixis, a key dimension of language governing the contextual anchoring of speech in interpersonal context. We designed naturalistic speech stimuli that were either non-personal and fact-reporting ('low-deixis' condition), or else involved rich deictic devices such as the grammatical first and second persons, direct questions, and vocatives ('high-deixis'). We asked whether neural correlates of deixis obtained with fMRI would distinguish patients with and without frequent hallucinations (AVH + vs AVH-) from controls and each other. Results showed that high-deixis relative to low-deixis was associated with clusters of increased activation in the bilateral middle temporal gyri extending into the temporal poles and the inferior parietal cortex, in all groups. The AVH + and AVH- groups did not differ. When unifying them, the SZ group as a whole showed altered activity in the precuneus, midline regions and inferior parietal cortex. These results fail to confirm deictic processing anomalies specific to patients with AVH, but reveal such anomalies across SZ. Hypoactivation of this network may relate to a cognitive mechanism for attributing and anchoring thought and referential speech content in context.

Breaking the flow of thought: Increase of empty pauses in the connected speech of people with mild and moderate Alzheimer's disease.

INTRODUCTION: The profile of spontaneous speech in Alzheimer's disease (AD) includes increased pausing as a window into cognitive decline. We here aimed to further characterize the pausing profile of AD by linking pauses to the syntactic positions in which they appear and disease progression. METHODS: Speech was obtained through a picture description task, thus minimizing demands on episodic memory (EM), from a group of mild (N = 21) and moderate AD (N = 19), and healthy elderly controls (N = 40). Pauses were sub-indexed according to whether they occurred within-clauses, clause-initially, or utterance-initially, and whether they preceded nouns, verbs, or adjectives/adverbs, when occurring within-clauses. Additionally, relations to verbal fluency (VF) measures at the single-word level were explored. RESULTS: Pause rate but not duration distinguished controls from both AD groups, while fillers did not distinguish any groups. The analysis by syntactic position revealed a highly differentiated picture, with largest effect sizes of significant group differences seen in the utterance-initial pause rate. The two AD groups patterned differently when compared to controls, while none of the measures differentiated the AD groups. Specifically, moderate but not mild AD differed from controls in clause-initial pauses, while mild but not moderate AD differed from controls in within-clause positions. At the within-clause level, the effect dividing controls from mild-AD was specifically driven by pauses ahead of nouns. A significant negative correlation emerged between pausing rate in spontaneous speech and VF measures in the mild-AD group only. CONCLUSIONS: Increased empty (non-filled) pauses in AD are not confined to pauses in within-clause positions, which are most directly related to problems in the retrieval of words. Even in early disease stages, where these within-clause pause effects are seen, they are confined to nouns, revealing a grammatically specific problem possibly related to the referencing of objects. At all disease stages, pauses increase in utterance-sized units of structure, indicating progressive problems in the creative configuration of complete thoughts.

Structural connectivity in ventral language pathways characterizes non-verbal autism.

Language capacities in autism spectrum disorders (ASD) range from normal scores on standardized language tests to absence of functional language in a substantial minority of 30% of individuals with ASD. Due to practical difficulties of scanning at this severe end of the spectrum, insights from MRI are scarce. Here we used manual deterministic tractography to investigate, for the first time, the integrity of the core white matter tracts defining the language connectivity network in non-verbal ASD (nvASD): the three segments of the arcuate (AF), the inferior fronto-occipital (IFOF), the inferior longitudinal (ILF) and the uncinate (UF) fasciculi, and the frontal aslant tract (FAT). A multiple case series of nine individuals with nvASD were compared to matched individuals with verbal ASD (vASD) and typical development (TD). Bonferroni-corrected repeated measure ANOVAs were performed separately for each tract-Hemisphere (2:Left/Right) × Group (3:TD/vASD/nvASD). Main results revealed (i) a main effect of group consisting in a reduction in fractional anisotropy (FA) in the IFOF in nvASD relative to TD; (ii) a main effect of group revealing lower values of radial diffusivity (RD) in the long segment of the AF in nvASD compared to vASD group; and (iii) a reduced volume in the left hemisphere of the UF when compared to the right, in the vASD group only. These results do not replicate volumetric differences of the dorsal language route previously observed in nvASD, and instead point to a disruption of the ventral language pathway, in line with semantic deficits observed behaviourally in this group.