Imagetic and affective measures of memory reverberation diverge at sleep onset in association with theta rhythm.

The 'day residue' - the presence of waking memories into dreams - is a century-old concept that remains controversial in neuroscience. Even at the psychological level, it remains unclear how waking imagery cedes into dreams. Are visual and affective residues enhanced, modified, or erased at sleep onset? Are they linked, or dissociated? What are the neural correlates of these transformations? To address these questions we combined quantitative semantics, sleep EEG markers, visual stimulation, and multiple awakenings to investigate visual and affect residues in hypnagogic imagery at sleep onset. Healthy adults were repeatedly stimulated with an affective image, allowed to sleep and awoken seconds to minutes later, during waking (WK), N1 or N2 sleep stages. 'Image Residue' was objectively defined as the formal semantic similarity between oral reports describing the last image visualized before closing the eyes ('ground image'), and oral reports of subsequent visual imagery ('hypnagogic imagery). Similarly, 'Affect Residue' measured the proximity of affective valences between 'ground image' and 'hypnagogic imagery'. We then compared these grounded measures of two distinct aspects of the 'day residue', calculated within participants, to randomly generated values calculated across participants. The results show that Image Residue persisted throughout the transition to sleep, increasing during N1 in proportion to the time spent in this stage. In contrast, the Affect Residue was gradually neutralized as sleep progressed, decreasing in proportion to the time spent in N1 and reaching a minimum during N2. EEG power in the theta band (4.5-6.5 Hz) was inversely correlated with the Image Residue during N1. The results show that the visual and affective aspects of the 'day residue' in hypnagogic imagery diverge at sleep onset, possibly decoupling visual contents from strong negative emotions, in association with increased theta rhythm.

The entropic tongue: Disorganization of natural language under LSD.

Serotonergic psychedelics have been suggested to mirror certain aspects of psychosis, and, more generally, elicit a state of consciousness underpinned by increased entropy of on-going neural activity. We investigated the hypothesis that language produced under the effects of lysergic acid diethylamide (LSD) should exhibit increased entropy and reduced semantic coherence. Computational analysis of interviews conducted at two different time points after 75 µg of intravenous LSD verified this prediction. Non-semantic analysis of speech organization revealed increased verbosity and a reduced lexicon, changes that are more similar to those observed during manic psychoses than in schizophrenia, which was confirmed by direct comparison with reference samples. Importantly, features related to language organization allowed machine learning classifiers to identify speech under LSD with accuracy comparable to that obtained by examining semantic content. These results constitute a quantitative and objective characterization of disorganized natural speech as a landmark feature of the psychedelic state.

Spatial distribution of buffy-tufted-ear (Callithrix aurita) and invasive marmosets (Callithrix spp.) in a tropical rainforest reserve in southeastern Brazil.

We investigated the spatial distribution of native and invasive marmoset species (Callithrix), as well as their hybrids, in the Serra dos Órgãos National Park (PARNASO) and surrounding area in Rio de Janeiro state, Brazil. To estimate occupancy and the detection probability, we surveyed 56 sites within the park and 52 sites outside its limits using vocal playbacks, as well as by interviewing local residents in the surrounding area. We estimated the occupancy and detection probability of Callithrix aurita and the observed groups composed of Callithrix jacchus, Callithrix penicillata, and their hybrids. We also recorded the presence or absence of mixed groups of native and exotic species, and their hybrids. We recorded similar occupancy rates and detection probabilities for both native and invasive species within the national park. C. aurita was found more often within the areas of the park located furthest from access roads and with the least human interference, while invasive species were more likely to be found along the edge of the park and in areas with greater human interference. In the area surrounding the park, invasive marmosets were recorded at seven sites, and a mixed group of native and invasive marmosets was observed at one site, but non-hybrid C. aurita groups were not recorded. The occupancy probability of C. aurita in the study area is relatively low, which may indicate a low population density, with groups restricted to a small region within the PARNASO in the proximity of groups of invasive marmosets.

Rare α0-thalassemia deletions detected by MLPA in five unrelated Brazilian patients.

Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..

The -(α)(5.2) Deletion Detected in a Uruguayan Family: First Case Report in the Americas.

In Uruguay, α-thalassemia (α-thal) mutations were introduced predominantly by Mediterranean European immigrant populations and by slave trade of African populations. A patient with anemia with hypochromia and microcytosis, refractory to iron treatment and with normal hemoglobin (Hb) electrophoresis was analyzed for α-thal mutations by multiplex gap-polymerase chain reaction (gap-PCR), automated sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses. Agarose gel electrophoresis of the multiplex gap-PCR showed a band of unexpected size (approximately 700 bp) in the samples from the proband and mother. Automated sequencing of the amplified fragment showed the presence of the -(α)(5.2) deletion (NG_000006.1: g.32867_38062del5196) [an α-thal-1 deletion of 5196 nucleotides (nts)]. The MLPA analysis of the proband's sample also showed the presence of the -(α)(5.2) deletion in heterozygous state. We report here the presence of the -(α)(5.2) deletion, for the first time in the Americas, in a Uruguayan family with Italian ancestry, detected with a previously described multiplex gap-PCR.

Computational Tracking of Mental Health in Youth: Latin American Contributions to a Low-Cost and Effective Solution for Early Psychiatric Diagnosis.

The early onset of mental disorders can lead to serious cognitive damage, and timely interventions are needed in order to prevent them. In patients of low socioeconomic status, as is common in Latin America, it can be hard to identify children at risk. Here, we briefly introduce the problem by reviewing the scarce epidemiological data from Latin America regarding the onset of mental disorders, and discussing the difficulties associated with early diagnosis. Then we present computational psychiatry, a new field to which we and other Latin American researchers have contributed methods particularly relevant for the quantitative investigation of psychopathologies manifested during childhood. We focus on new technologies that help to identify mental disease and provide prodromal evaluation, so as to promote early differential diagnosis and intervention. To conclude, we discuss the application of these methods to clinical and educational practice. A comprehensive and quantitative characterization of verbal behavior in children, from hospitals and laboratories to homes and schools, may lead to more effective pedagogical and medical intervention.

Speech connectedness predicts reading performance three months in advance: a longitudinal experiment.

Aiming to verify the predictive value of oral narrative structure on reading acquisition, we followed 253 children (first and second graders) during an entire school year, assessing oral narratives and reading performances in five sessions. Transcriptions of oral narratives were represented as word-recurrence graphs to measure connectedness attributes. Connectedness predicted performance in phonological awareness, reading comprehension, and word reading accuracy 3-4 months in advance.

How can computational tools help to understand language patterns in mental suffering considering social diversity.

The complex interaction between biological and social factors challenges measuring human behavior. Language has been a crucial source of information that mirrors inner processes like thoughts. The development of a novel computational strategy that helps to understand language needs to consider social factors that could also impact human behavior. Ten years ago, I developed a computational approach based on graph theory to measure structural aspects of the narrative's mental organization expressed in spontaneous oral reports. It was possible to measure the decrease in narrative graph connectedness associated with the schizophrenia diagnosis and negative symptoms severity. However, I was worried that the psychiatric field neglected factors from diverse social realities (such as poor access to education). Formal education impacts language by mastering grammar and syntax. Changes in language structure could be related to symptoms and lack of exposure to formal education. Indeed, the same connectedness markers increase according to typical cognitive and academic development. In this paper, I describe the reasons and methods for investigating both factors (psychiatric symptoms and formal education) on language patterns. Further, I evaluate concerns and future challenges of using computational strategies that include social diversity in mental health conditions.

Grammatical impairment in schizophrenia: An exploratory study of the pronominal and sentential domains.

Schizophrenia (SZ) is a severe mental disorder associated with a variety of linguistic deficits, and recently it has been suggested that these deficits are caused by an underlying impairment in the ability to build complex syntactic structures and complex semantic relations. Aiming at contributing to determining the specific linguistic profile of SZ, we investigated the usage of pronominal subjects and sentence types in two corpora of oral dream and waking reports produced by speakers with SZ and participants without SZ (NSZ), both native speakers of Brazilian Portuguese. Narratives of 40 adult participants (20 SZ, and 20 NSZ-sample 1), and narratives of 31 teenage participants (11 SZ undergoing first psychotic episode, and 20 NSZ-sample 2) were annotated and statistically analyzed. Overall, narratives of speakers with SZ presented significantly higher rates of matrix sentences, null pronouns-particularly null 3Person referential pronouns-and lower rates of non-anomalous truncated sentences. The high rate of matrix sentences correlated significantly with the total PANSS scores, suggesting an association between the overuse of simple sentences and SZ symptoms in general. In contrast, the high rate of null pronouns correlated significantly with positive PANSS scores, suggesting an association between the overuse of null pronominal forms and the positive symptoms of SZ. Finally, a cross-group analysis between samples 1 and 2 indicated a higher degree of grammatical impairment in speakers with multiple psychotic episodes. Altogether, the results strengthen the notion that deficits at the pronominal and sentential levels constitute a cross-cultural linguistic marker of SZ.

Happy thoughts: What computational assessment of connectedness and emotional words can inform about early stages of psychosis.

In recent years, different natural language processing tools measured aspects related to narratives' structural, semantic, and emotional content. However, there is a need to better understand the limitations and effectiveness of speech elicitation protocols. The graph-theoretical analysis applied to short narratives reveals lower connectedness associated with negative symptoms even in the early stages of psychosis, but emotional topics seem more informative than others. We investigate the interaction between connectedness and emotional words with negative symptoms and educational level in participants with and without psychosis. For that purpose, we used a speech elicitation protocol based on three positive affective pictures and calculated the proportion of emotional words and connectedness measures in the first-episode psychosis (FEP) group (N: 24) and a control group (N: 33). First, we replicated the association between connectedness and negative symptoms (R2: 0.53, p: 0.0049). Second, the more positive terms, the more connected the narrative was, exclusively under psychosis and in association with education, pointing to an interaction between symptoms and formal education. Negative symptoms were independently associated with connectedness, but not with emotional words, although the associations with education were mutually dependent. Together, education and symptoms explained almost 70 % of connectedness variance (R2: 0.67, p < 0.0001), but not emotional expression. At this initial stage of psychosis, education seems to play an important role, diminishing the impact of negative symptoms on the narrative connectedness. Negative symptoms in FEP impact narrative connectedness in association with emotional expression, revealing aspects of social cognition through a short and innocuous protocol.

Hakuna MAM-Tata: Investigating the role of mitochondrial-associated membranes in ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease leading to selective and progressive motor neuron (MN) death. Despite significant heterogeneity in pathogenic and clinical terms, MN demise ultimately unifies patients. Across the many disturbances in neuronal biology present in the disease and its models, two common trends are loss of calcium homeostasis and dysregulations in lipid metabolism. Since both mitochondria and endoplasmic reticulum (ER) are essential in these functions, their intertwin through the so-called mitochondrial-associated membranes (MAMs) should be relevant in this disease. In this review, we present a short overview of MAMs functional aspects and how its dysfunction could explain a substantial part of the cellular disarrangements in ALS's natural history. MAMs are hubs for lipid synthesis, integrating glycerophospholipids, sphingolipids, and cholesteryl ester metabolism. These lipids are essential for membrane biology, so there should be a close coupling to cellular energy demands, a role that MAMs may partially fulfill. Not surprisingly, MAMs are also host part of calcium signaling to mitochondria, so their impairment could lead to mitochondrial dysfunction, affecting oxidative phosphorylation and enhancing the vulnerability of MNs. We present data supporting that MAMs' maladaptation could be essential to MNs' vulnerability in ALS.

Speech graph analysis in obsessive-compulsive disorder: The relevance of dream reports.

Obsessive-compulsive disorder (OCD) is a distressing disorder characterized by the presence of intrusive thoughts, images or urges (obsessions) and/or behavioral efforts to reduce the anxiety (compulsions). OCD lifetime prevalence varies between 1% and 3% in the general population and there are no reliable markers that support the diagnosis. In order to fill this gap, Computational Psychiatry employs multiple types of quantitative analyses to improve the understanding, diagnosis, prediction, and treatment of mental illnesses including OCD. One of these computational tools is speech graphs analysis. A graph represents a network of nodes connected by edges: in non-semantic speech graphs, nodes correspond to words and edges correspond to the directed link between consecutive words. Using non-semantic speech graphs, we compared free speech samples from OCD patients and healthy controls (HC), to test whether speech graphs analysis can grasp structural differences in speech between these groups. To this end, 39 OCD patients and 37 HC were interviewed and recorded during six types of speech reports: yesterday, dream, old memory, positive image, negative image and neutral image. Also, the Obsessive-Compulsive Inventory-Revised (OCI-R) and the Yale Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess symptom severity. The graph-theoretical structural analysis of dream reports showed that OCD patients have significantly smaller lexical diversity, lower speech connectedness and a higher recurrence of words in comparison with HC. The other five report types failed to show differences between the groups, adding to the notion that dream reports are especially informative of speech structure in different psychiatric states. Further investigation is necessary to completely assess the potential of this tool in OCD.

Speech as a Graph: Developmental Perspectives on the Organization of Spoken Language.

Language has been used as a privileged window to investigate mental processes. More recently, descriptions of psychopathological symptoms have been analyzed with the help of natural language processing tools. An example is the study of speech organization using graph theoretical approaches that began approximately 10 years ago. After its application in different areas, there is a need to better characterize what aspects can be associated with typical and atypical behavior throughout the lifespan, given the variables related to aging as well as biological and social contexts. The precise quantification of mental processes assessed through language may allow us to disentangle biological/social markers by looking at naturalistic protocols in different contexts. In this review, we discuss 10 years of studies in which word recurrence graphs were adopted to characterize the chain of thoughts expressed by individuals while producing discourse. Initially developed to understand formal thought disorder in the context of psychotic syndromes, this line of research has been expanded to understand the atypical development in different stages of psychosis and differential diagnosis (such as dementia) as well as the typical development of thought organization in school-age children/teenagers in naturalistic and school-based protocols. We comment on the effects of environmental factors, such as education and reading habits (in monolingual and bilingual contexts), in clinical and nonclinical populations at different developmental stages (from childhood to older adulthood, considering aging effects on cognition). Looking toward the future, there is an opportunity to use word recurrence graphs to address complex questions that consider biological/social factors within a developmental perspective in typical and atypical contexts.

Syntactic Network Analysis in Schizophrenia-Spectrum Disorders.

BACKGROUND: Language anomalies are a hallmark feature of schizophrenia-spectrum disorders (SSD). Here, we used network analysis to examine possible differences in syntactic relations between patients with SSD and healthy controls. Moreover, we assessed their relationship with sociodemographic factors, psychotic symptoms, and cognitive functioning, and we evaluated whether the quantification of syntactic network measures has diagnostic value. STUDY DESIGN: Using a semi-structured interview, we collected speech samples from 63 patients with SSD and 63 controls. Per sentence, a syntactic representation (ie, parse tree) was obtained and used as input for network analysis. The resulting syntactic networks were analyzed for 11 local and global network measures, which were compared between groups using multivariate analysis of covariance, considering the effects of age, sex, and education. RESULTS: Patients with SSD and controls significantly differed on most syntactic network measures. Sex had a significant effect on syntactic measures, and there was a significant interaction between sex and group, as the anomalies in syntactic relations were most pronounced in women with SSD. Syntactic measures were correlated with negative symptoms (Positive and Negative Syndrome Scale) and cognition (Brief Assessment of Cognition in Schizophrenia). A random forest classifier based on the best set of network features distinguished patients from controls with 74% cross-validated accuracy. CONCLUSIONS: Examining syntactic relations from a network perspective revealed robust differences between patients with SSD and healthy controls, especially in women. Our results support the validity of linguistic network analysis in SSD and have the potential to be used in combination with other automated language measures as a marker for SSD.

LSD and language: Decreased structural connectivity, increased semantic similarity, changed vocabulary in healthy individuals.

Language has been explored as a window into the mind. Psychedelics, known to affect perception and cognition, seem to change language, but a systematic, time-dependent exploration is lacking. Therefore, we aimed at mapping the psychedelic effects on language over the time course of the acute and sub-acute effects in an explorative manner. For this, 24 healthy volunteers (age [mean±SD, range]: 35±11, 25-61 years; 33% women) received 50 µg lysergic acid diethylamide (LSD) or inactive placebo in a randomized, double-blind, placebo-controlled, crossover study. We assessed different language productions (experience reporting, storytelling), components (structure, semantics, vocabulary) and time points (+0 h to +24 h). Language productions included 5-min experience reporting (+1.5 h, +6.5 h) and 1-min storytelling (+0 h, +2 h, +4 h, +6 h, +24 h). Language structure was assessed by computing speech topology (SpeechGraphs), semantics by semantic distances (FastText), vocabulary by word categories (LIWC). LSD, compared to placebo, changed language structure, including decreased verbosity, lexicon, global and local connectivity (+1.5 h to +4 h); decreased semantic distances between neighbouring words and overall words (+2 h to +24 h); and changed vocabulary related to grammar, persons, time, space and biological processes (+1.5 h to +24 h). In conclusion, low to moderate LSD doses changed language over diverse production types, components and time points. While simpler and disconnected structure and semantic similarity might reflect cognitive impairments, changed vocabulary might reflect subjective perceptions. Therefore, language under LSD might provide a window into the psychedelic mind and automated language quantifications should be better explored as valuable tools to yield more unconstrained insights into psychedelic perception and cognition.

Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features.

AIMS: Our study aimed to develop a machine learning ensemble to distinguish "at-risk mental states for psychosis" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings. METHODS: 58 non-help-seeking medication-naïve ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and "Subject's Overview" section was filmed (5-10 min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used. RESULTS: Final model reached 83 % of mean F1-score, and balanced accuracy of 85 %. Mean area under the curve for the receiver operator curve classifier was 93 %. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item). CONCLUSION: Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.

Gesticulation in individuals with at risk mental states for psychosis.

Nonverbal communication (NVC) is a complex behavior that involves different modalities that are impaired in the schizophrenia spectrum, including gesticulation. However, there are few studies that evaluate it in individuals with at-risk mental states (ARMS) for psychosis, mostly in developed countries. Given our prior findings of reduced movement during speech seen in Brazilian individuals with ARMS, we now aim to determine if this can be accounted for by reduced gesticulation behavior. Fifty-six medication-naïve ARMS and 64 healthy controls were filmed during speech tasks. The frequency of specifically coded gestures across four categories (and self-stimulatory behaviors) were compared between groups and tested for correlations with prodromal symptoms of the Structured Interview for Prodromal Syndromes (SIPS) and with the variables previously published. ARMS individuals showed a reduction in one gesture category, but it did not survive Bonferroni's correction. Gesture frequency was negatively correlated with prodromal symptoms and positively correlated with the variables of the amount of movement previously analyzed. The lack of significant differences between ARMS and control contradicts literature findings in other cultural context, in which a reduction is usually seen in at-risk individuals. However, gesture frequency might be a visual proxy of prodromal symptoms, and of other movement abnormalities. Results show the importance of analyzing NVC in ARMS and of considering different cultural and sociodemographic contexts in the search for markers of these states.

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.

Graph structure analysis of speech production among second language learners of Spanish and Chinese.

Language experience shapes the gradual maturation of speech production in both native (L1) and second (L2) languages. Structural aspects like the connectedness of spontaneous narratives reveal this maturation progress in L1 acquisition and, as it does not rely on semantics, it could also reveal structural pattern changes during L2 acquisition. The current study tested whether L2 lexical retrieval associated with vocabulary knowledge could impact the global connectedness of narratives during the initial stages of L2 acquisition. Specifically, the study evaluated the relationship between graph structure (long-range recurrence or connectedness) and L2 learners' oral production in the L2 and L1. Seventy-nine college-aged students who were native speakers of English and had received classroom instruction in either L2-Spanish or L2-Chinese participated in this study. Three tasks were used: semantic fluency, phonemic fluency and picture description. Measures were operationalized as the number of words per minute in the case of the semantic and phonemic fluency tasks. Graph analysis was carried out for the picture description task using the computational tool SpeechGraphs to calculate connectedness. Results revealed significant positive correlations between connectedness in the picture description task and measures of speech production (number of correct responses per minute) in the phonemic and semantic fluency tasks. These correlations were only significant for the participants' L2- Spanish and Chinese. Results indicate that producing low connectedness narratives in L2 may be a marker of the initial stages of L2 oral development. These findings are consistent with the pattern reported in the early stages of L1 literacy. Future studies should further explore the interactions between graph structure and second language production proficiency, including more advanced stages of L2 learning and considering the role of cognitive abilities in this process.

Reading and writing habits compensate for aging effects in speech connectedness.

We investigate the association of short- and long-range recurrences (speech connectedness) with age, education, and reading and writing habits (RWH) in typical aging using an oral narrative production task. Oral narrative transcriptions were represented as word-graphs to measure short- and long-range recurrences. Speech connectedness was explained by the combination of age, education, and RWH, and the strength of RWH's coefficient reflects the aging effect.