Brain and grammar: revealing electrophysiological basic structures with competing statistical models.

Acoustic, lexical, and syntactic information are simultaneously processed in the brain requiring complex strategies to distinguish their electrophysiological activity. Capitalizing on previous works that factor out acoustic information, we could concentrate on the lexical and syntactic contribution to language processing by testing competing statistical models. We exploited electroencephalographic recordings and compared different surprisal models selectively involving lexical information, part of speech, or syntactic structures in various combinations. Electroencephalographic responses were recorded in 32 participants during listening to affirmative active declarative sentences. We compared the activation corresponding to basic syntactic structures, such as noun phrases vs. verb phrases. Lexical and syntactic processing activates different frequency bands, partially different time windows, and different networks. Moreover, surprisal models based on part of speech inventory only do not explain well the electrophysiological data, while those including syntactic information do. By disentangling acoustic, lexical, and syntactic information, we demonstrated differential brain sensitivity to syntactic information. These results confirm and extend previous measures obtained with intracranial recordings, supporting our hypothesis that syntactic structures are crucial in neural language processing. This study provides a detailed understanding of how the brain processes syntactic information, highlighting the importance of syntactic surprisal in shaping neural responses during language comprehension.

Mortality of alzheimer's disease in Italy from 1980 to 2015.

OBJECTIVE: To evaluate mortality for Alzheimer's Disease (AD) in Italy over more than three decades (1980-2015) and discuss the possible role of general and specific contributing factors. METHODS: Mortality data were extracted by the Italian National Institute of Statistics: crude mortality rates were computed for sex and age, considering the whole country and its five main geographical sub-areas. Rates were standardized in two ways: directly (annual mortality rates AMRs) and indirectly (standardized mortality rates, SMRs). SMRs were then used to evaluate geographical differences; to study mortality trend, AMRs and joinpoint linear regression analysis were used. RESULTS: Considering the entire period and the whole country, mortality rates were similar for females and males and for geographical regions, with the exception of the older age groups where mortality for AD in females slightly prevailed. In these older patients, a steep increase of mortality was seen starting from the current century. The increase in male mortality mirrored the national trend in North-West and Central Italy, but not in North-East, South, and the Islands, where it did not surge until the mid to late 1990s. CONCLUSIONS: the general increase of mortality is in line with international data and it reflects the increasing prevalence of the disease, likely due to increasing longevity, and to improvements in diagnostic accuracy. In addition, the accuracy of death certificate compilation could account for both geographical and temporal differences. Currently available drugs for AD do not seem to have an impact on mortality rates.

A digital teleneuropsychology platform for the diagnosis of mild cognitive impairment: from concept to certification as a medical device.

BACKGROUND: Innovative digital solutions are shaping a new concept of dementia care, opening additional venues for prevention, diagnosis, monitoring and treatment. Hereby, we report the development of a tablet-based teleneuropsychology platform (Tenèpsia®), from concept to certification as Medical Device (MD) Class IIA, as per new MD regulation 745/2017. METHODS: The platform was designed for the remote cognitive evaluation and created thanks to the effort of a collaborative working group including experts from three Italian scientific societies and Biogen Italia S.r.l. (hereafter "Biogen"), and developers from Xenia Reply and Inside AI. The development strategy was guided by converting traditional paper-and-pencil tests into digital versions while maintaining comparable neuropsychological features and optimizing patient accessibility and user experience. The experts focused on the choice and adaptation of traditional neuropsychology measures for a 45-min teleneuropsychology assessment. RESULTS: The developers created a web and a mobile interface, respectively, for the professional (neuropsychologist) and non-professional (patient and caregiver) use. Recording of voice, drawing and typing information was enabled. Instant dashboards provide a quick overview of the patient's condition. Simulation activities were performed to obtain MD certification, valid across Europe. CONCLUSION: Neuropsychology services will benefit from the implementation in clinics of harmonized digital tools with adequate scientific and technological standards. The use of digital cognitive testing for the diagnosis of mild cognitive impairment is expected to enhance patient and clinician outcomes through simplified, digital objective data collection, sparing of time and resources, with a positive impact on healthcare costs and access to treatments, reducing inequalities and delays in diagnosis and cure.

Subjective cognitive decline: Memory complaints, cognitive awareness, and metacognition.

Cognitive complaints are common in elderly subjects and are a frequent reason for referral to memory clinics. If the complaints are not associated with objective cognitive impairment, the condition is labelled subjective cognitive decline (SCD). SCD is often considered as a stage antedating objective impairment, and an at-risk condition for subsequent dementia. Recent large-scale studies indicate that a significantly increased risk of clinical progression in subjects with SCD is associated with positivity for Alzheimer's disease (AD) biomarkers, a finding supporting the notion that SCD can be due to different mechanisms not associated with neurodegeneration, including functional cognitive disorders. In this paper we present a selective review of research on the relations among SCD, cognitive awareness, and metacognitive abilities. We propose that longitudinal studies of metacognitive efficiency in SCD may provide useful cues about the risk of progression to dementia and the possible presence of a functional cognitive disorder, with different implications for the management of this prevalent aging-related condition. HIGHLIGHTS: Subjective cognitive decline (SCD), a common cause of referral to memory clinics, can be due to multiple conditions. The predictive value of SCD for progression to Alzheimer's disease (AD) dementia is high in association with AD biomarker positivity. The awareness of cognitive decline is the mechanism responsible for the emergence of SCD and metacognition is the underlying neuropsychological function. The awareness of cognitive decline in clinical patients is usually assessed comparing an informant rating to the patient self-assessment, a method that can be affected by informant bias. While there is strong evidence that awareness starts to decline with the onset of objective cognitive impairment, progressively leading to the anosognosia of AD, the status of metacognitive efficiency in SCD needs to be further investigated. Quantitative, performance-based indexes of metacognitive efficiency may contribute both to the assessment of progression risk and to the management of subjects with functional cognitive disorders.

TACO: A Turkish database for abstract concepts.

The organization of abstract concepts reflects different dimensions, grounded in the brain regions coding for the corresponding experience. Normative measures of linguistic stimuli offer noteworthy insights into the organization of conceptual knowledge, but studies differ in the dimensions and classes of concepts considered. Additionally, most of the available information has been collected in English, without considering possible linguistic and cultural differences. Here, we aimed to create a comprehensive Turkish database for abstract concepts (TACO), including rarely investigated classes such as political concepts. We included 503 words-78 concrete (fruits, animals, tools) and 425 abstract (emotions, social, mental states, theoretical, quantity, space, political)-rated by 134 Turkish speakers for familiarity, imageability, age of acquisition, valence, arousal, quantity, space, theoretical, social, mental state, and political dimensions. We calculated dominance and exclusivity, indicating the dimension receiving the highest mean score for each word, and the position of the word along the unidimensional-multidimensional continuum, respectively. A principal component analysis (PCA) was conducted on the semantic dimensions. The results showed that mental state was the dominant dimension for most concepts. Moderate to low levels of exclusivity indicated that the concepts were multidimensional. PCA revealed three components: Component 1 captured the juxtaposition between social/mental state and magnitude polarities, Component 2 highlighted affective components, and Component 3 grouped together political and theoretical dimensions. The introduction of political concepts provided insights into the multidimensional nature of this unexplored class, closely intertwined with the theoretical dimension. TACO constitutes the first comprehensive Turkish database covering several abstract dimensions, paving the way for cross-linguistic and cross-cultural studies of semantic representations.

Feasibility of a standard cognitive assessment in European academic memory clinics.

INTRODUCTION: Standardized cognitive assessment would enhance diagnostic reliability across memory clinics. An expert consensus adapted the Uniform Dataset (UDS)-3 for European centers, the clinician's UDS (cUDS). This study assessed its implementation acceptability and feasibility. METHODS: We developed a survey investigating barriers, facilitators, and willingness to implement the cUDS. With a mixed-methods design, we analyzed data from academic memory clinics. RESULTS: Seventy-eight percent of responding clinicians were experienced neuropsychologists/psychologists and 22% were medical specialists coming from 18 European countries. Sixty-five percent clinicians were willing to implement cUDS. General barriers related to implementation (43%) and clinical-methodological domains (21%). Favorable clinicians reported finances (15%) and digitalization (9%) as facilitating, but unavailability of local norms (23%) as hindering. Unfavorable clinicians reported logistical (23%) and time issues (18%). DISCUSSION: Despite challenges, data showed moderate clinicians' acceptability and requirements to improve feasibility. Nonetheless, these results come from academic clinicians. The next steps will require feasibility evaluation in non-academic contexts.

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus.

INTRODUCTION: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome. METHODS: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria. RESULTS: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes. DISCUSSION: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

Emotion Recognition Deficits in the Differential Diagnosis of Amnestic Mild Cognitive Impairment: A Cognitive Marker for the Limbic-Predominant Phenotype.

OBJECTIVE: Late-onset amnestic mild cognitive impairment (aMCI) with long disease course and slow progression has been recently recognized as a possible phenotypical expression of a limbic-predominant neurodegenerative disorder. Basic emotion recognition ability crucially depending on temporo-limbic integrity is supposed to be impaired in this group of MCI subjects presenting a selective vulnerability of medio-temporal and limbic regions. However, no study specifically investigated this issue. METHODS: Hereby, we enrolled 30 aMCI with a biomarker-based diagnosis of Alzheimer's disease (i.e., aMCI-AD, n = 16) or a biomarker evidence of selective medio-temporal and limbic degeneration (aMCI-mTLD, n = 14). Ekman-60 Faces Test (Ek-60F) was administered to each subject, comparing the performance with that of 20 healthy controls (HCs). RESULTS: aMCI-mTLD subjects showed significantly lower Ek-60F global scores compared to HC (p = 0.001), whose performance was comparable to aMCI-AD. Fear (p = 0.02), surprise (p = 0.005), and anger (p = 0.01) recognition deficits characterized the aMCI-mTLD performance. Fear recognition scores were significantly lower in aMCI-mTLD compared to aMCI-AD (p = 0.04), while no differences were found in other emotions. CONCLUSIONS: Impaired social cognition, suggested by defective performance in emotion recognition tasks, may be a useful cognitive marker to detect limbic-predominant aMCI subjects among the heterogeneous aMCI population.

Development and internal validation of a prognostic model for 15-year risk of Alzheimer dementia in primary care patients.

BACKGROUND: The exploitation of routinely collected clinical health information is warranted to optimize the case detection and diagnostic workout of Alzheimer's disease (AD). We aimed to derive an AD prediction score based on routinely collected primary care data. METHODS: We built a cohort selecting 199,978 primary care patients 60 + part of the Health Search Database between January 2002 and 2009, followed up until 2019 to detect incident AD cases. The cohort was randomly divided into a derivation and validation sub-cohort. To identify AD and non-AD cases, we applied a clinical algorithm that involved two clinicians. According to a nested case-control design, AD cases were matched with up to 10 controls based on age, sex, calendar period, and follow-up duration. Using the derivation sub-cohort, 32 potential AD predictors (sociodemographic, clinical, drug-related, etc.) were tested in a logistic regression and selected to build a prediction model. The predictive performance of this model was tested on the validation sub-cohort by mean of explained variation, calibration, and discrimination measurements. RESULTS: We identified 3223 AD cases. The presence of memory disorders, hallucinations, anxiety, and depression and the use of NSAIDs were associated with future AD. The combination of the predictors allowed the production of a predictive score that showed an explained variation (pseudo-R2) for AD occurrence of 13.4%, good calibration parameters, and an area under the curve of 0.73 (95% CI: 0.71-0.75). In accordance with this model, 7% of patients presented with a high-risk score for developing AD over 15 years. CONCLUSION: An automated risk score for AD based on routinely collected clinical data is a promising tool for the early case detection and timely management of patients by the general practitioners.

Evaluation of Discriminative Detection Abilities of Social Cognition Measures for the Diagnosis of the Behavioral Variant of Frontotemporal Dementia: a Systematic Review.

The use of social tasks in the neuropsychological assessment of the behavioral variant of frontotemporal dementia (bvFTD) is at present not required by diagnostic guidelines, despite extensive literature shows relevant social cognitive dysfunctions in such patients. In this systematic review, we explored the clinical maturity of social cognition measures in the diagnosis of bvFTD. Papers were selected according to the PRISMA guidelines by searching the PubMed and Medline databases. Only papers reporting indices of diagnostic accuracy and/or sensitivity/specificity in classifying bvFTD from controls or from other relevant diseases were considered. Quality of evidence was assessed through QUADAS-2. Among the 663 articles entered in the paper selection only 14 papers were eligible for the scope of the present review and showed an overall moderate-to-low quality. The major risk of bias was the lack of pathological confirmation. The evaluation of the accuracy of social cognition tasks in bvFTD detection compared to normal controls, as well as in the discrimination with Alzheimer's disease and psychiatric patients, is mainly focused on emotion recognition and theory of mind. However, the use of different cognitive measures, variable task formats and the limited normative data hamper study comparability. Although literature seems to suggest that emotion recognition and ToM tasks could be the best choice to ensure a high diagnostic accuracy in clinical settings, further comparative studies are required and no recommendation concerning the use of a specific social task in bvFTD diagnosis can be currently provided.

Cortical correlates of behavioural change in amyotrophic lateral sclerosis.

BACKGROUND: Behavioural changes in amyotrophic lateral sclerosis (ALS) are heterogeneous. The study aim was to identify the behavioural profiles of non-demented patients with ALS and their neuroimaging correlates and to elucidate if they are comparable to those reported in studies of the behavioural-variant of frontotemporal dementia (bvFTD). METHODS: Behavioural changes of 102 non-demented patients with ALS were assessed through the Frontal Behavioural Inventory (FBI), a 24-item scale assessing different behavioural modifications, mainly chosen from the core clinical features of FTD. Principal component analysis (PCA) was used to detect distinct clusters of behavioural changes based on FBI subscores. The cortical thinning related to each behavioural profile was analysed in 29 patients with ALS. Cronbach's α was used to test the reliability of bvFTD-related FBI clustering in our cohort. RESULTS: Sixty patients with ALS had FBI score≥1. PCA identified three phenotypic clusters loading on disinhibited/hostile, dysexecutive and apathetic FBI subscores. Imaging analyses revealed that the thinning of bilateral orbitofrontal cortex was related to apathy, the right frontotemporal and cingular cortex to the disinhibited/hostile profile and the left precuneus cortex to the dysexecutive behaviours. The bvFTD-associated aggressive profile reliably applied to our cohort. CONCLUSIONS: In non-demented patients with ALS, different behavioural profiles could be identified. The right frontotemporal and cingular cortex thinning was the hallmark of the behavioural profile mostly overlapping that described in bvFTD. Our findings provide the unbiased identification of determinants relevant for a novel stratification of patients with ALS based on their behavioural impairment, which might be useful as proxy of cognitive decline.

The left inferior frontal gyrus: A neural crossroads between abstract and concrete knowledge.

Evidence from both neuropsychology and neuroimaging suggests that different types of information are necessary for representing and processing concrete and abstract word meanings. Both abstract and concrete concepts, however, conjointly rely on perceptual, verbal and contextual knowledge, with abstract concepts characterized by low values of imageability (IMG) (low sensory-motor grounding) and low context availability (CA) (more difficult to contextualize). Imaging studies supporting differences between abstract and concrete concepts show a greater recruitment of the left inferior frontal gyrus (LIFG) for abstract concepts, which has been attributed either to the representation of abstract-specific semantic knowledge or to the request for more executive control than in the case of concrete concepts. We conducted an fMRI study on 27 participants, using a lexical decision task involving both abstract and concrete words, whose IMG and CA values were explicitly modelled in separate parametric analyses. The LIFG was significantly more activated for abstract than for concrete words, and a conjunction analysis showed a common activation for words with low IMG or low CA only in the LIFG, in the same area reported for abstract words. A regional template map of brain activations was then traced for words with low IMG or low CA, and BOLD regional time-series were extracted and correlated with the specific LIFG neural activity elicited for abstract words. The regions associated to low IMG, which were functionally correlated with LIFG, were mainly in the left hemisphere, while those associated with low CA were in the right hemisphere. Finally, in order to reveal which LIFG-related network increased its connectivity with decreases of IMG or CA, we conducted generalized psychophysiological interaction analyses. The connectivity strength values extracted from each region connected with the LIFG were correlated with specific LIFG neural activity for abstract words, and a regression analysis was conducted to highlight which areas recruited by low IMG or low CA predicted the greater activation of the IFG for abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be involved in semantic processing, was a significant predictor of LIFG activity differentiating abstract from concrete words. The results show that the abstract conceptual processing requires the interplay of multiple brain regions, necessary for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG can be thus identified as the neural crossroads between different types of information equally necessary for representing processing and differentiating abstract concepts from concrete ones.

Mediterranean Diet and Cognitive Status in Free-Living Elderly: A Cross-Sectional Study in Northern Italy.

OBJECTIVE: Few data are available on the Italian elderly population with regard to adherence to the Mediterranean diet (MD) and cognitive impairment. Our aim was to investigate adherence to the MD and its association with cognitive function in an Italian urban sample. METHODS: A cross-sectional study of 279 participants aged ≥ 65 years (80 men, 199 women) was carried out at a nutritional center. Adherence to the MD was evaluated using a 14-item questionnaire. Cognitive function was assessed with the Mini-Mental State Examination (MMSE). RESULTS: The clinical and nutritional assessments performed revealed 30.1% to have a dietary pattern in accordance with the MD; 13.6% had suspected or mild cognitive impairment (MMSE score ≤ 23). The MD pattern was associated with a lower risk of cognitive impairment (odds ratio [OR] = 0.39; 95% confidence interval [CI], 0.15-0.99; p = 0.045), as was the consumption of wine (OR = 0.37; 95% CI, 0.16-0.84; p = 0.018) and nuts (OR = 0.30; 95% CI, 0.13-0.69, p = 0.005). No association was found with other food groups. CONCLUSION: A closer adherence to the MD was associated with a better cognitive status. Further cohort studies and randomized controlled trials are warranted.

Screening for Aphasia in NeuroDegeneration for the Diagnosis of Patients with Primary Progressive Aphasia: Clinical Validity and Psychometric Properties.

BACKGROUND: We evaluated the psychometric proprieties of the Screening for Aphasia in NeuroDegeneration (SAND) battery in Italian primary progressive aphasia (PPA) and movement disorder (MD) patients. METHODS: The sample included 30 consecutive PPA and 45 MD patients who completed the SAND battery together with a clinical interview and a neurological/neuropsychological examination and 130 healthy controls (HC). RESULTS: The SAND battery showed good internal consistency and good convergent and divergent validity. receiver operating characteristic analysis revealed an area under the curve of 0.978 for PPA versus HC and of 0.786 for PPA versus MD. A cutoff ≥3 gave a sensitivity of 0.933% and a specificity of 0.946% for discriminating PPA versus HC, whereas a cutoff ≥5 gave a sensitivity of 0.767% and a specificity of 0.667% for discriminating PPA versus MD. CONCLUSION: These results indicate that the SAND battery is an adequate, reliable, and valid diagnostic tool for PPA.

Improving innovative decision-making: Training-induced changes in fronto-parietal networks.

Innovative decision-making entails the balance of exploitative and explorative choices, and has been linked to the efficiency of executive functioning, including working-memory and attentional skills, associated with fronto-parietal networks. Based on the notion that such skills can be improved by cognitive training, we assessed whether a cognitive training enhancing basic executive skills might also improve the ability to manage the exploration-exploitation trade-off and its financial consequences, and whether any improvement in training-related performance would be reflected in neurostructural changes within fronto-parietal networks. Eighteen subjects participated in a baseline assessment, a training period and a follow-up measurement, while a matched group of 18 subjects did not undertake the training program. A subgroup of subjects underwent a multimodal MRI study to explore training-related changes in grey-matter volume and white-matter microstructure. After training, increased efficiency of innovative decision-making, related to the improvement of executive control skills, reflected neurostructural changes involving the right fronto-polar cortex and left superior longitudinal fasciculus. The quality of innovative decision-making can be improved by ad-hoc cognitive training procedures focused on executive skills, promoting neurostructural changes in fronto-parietal networks. The manifold implications involve both managerial and rehabilitative settings concerned with the quality of choices in normal and pathological conditions, respectively.

Free and cued selective reminding test predicts progression to Alzheimer's disease in people with mild cognitive impairment.

INTRODUCTION: To assess the diagnostic accuracy of the free and cued selective reminding test (FCSRT) for the development of Alzheimer's disease (AD) in people with mild cognitive impairment (MCI). METHODS: We enrolled 187 consecutive MCI outpatients from a memory clinic that were evaluated at baseline and every 6 to 12 months through an extensive clinical and neuropsychological protocol. For each test, measures of diagnostic accuracy were obtained. To improve the overall specificity of the neuropsychological battery, we also used the diagnostic tests in parallel combination. The association between FCSRT indexes and AD was tested through proportional hazard regression models with other dementia subtypes as competing event. Laplace regression was used to model time-to-AD diagnosis as a function of FCSRT indexes. RESULTS: The area under the curve of the FCSRT indexes ranged from 0.69 (95% CI: 0.62-0.76) to 0.76 (95% CI: 0.70-0.82). The specificity peaked up to 100% when we combined the category fluency test with the delayed total recall index of the FCSRT. Participants who tested positive at the FCSRT, as compared with those with negative tests, presented a twofold to fivefold higher risk of developing AD (median follow-up time 2.5 years; p < 0.001) and were diagnosed with AD 2-3 years earlier (p < 0.001). DISCUSSION: The FCSRT assessment suite shows the best predictive performance in detecting AD in people with MCI. These findings might help to reliably and timely identify people at higher risk of AD that is crucial both for properly selecting participants to clinical trials and to fine tune an effective and patient-centered care.

Neural markers of loss aversion in resting-state brain activity.

Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice.

Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.

Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control.

Effective connectivity gateways to the Theory of Mind network in processing communicative intention.

An Intention Processing Network (IPN), involving the medial prefrontal cortex, precuneus, bilateral posterior superior temporal sulcus, and temporoparietal junctions, plays a fundamental role in comprehending intentions underlying action goals. In a previous fMRI study, we showed that, depending on the linguistic or extralinguistic (gestural) modality used to convey the intention, the IPN is complemented by activation of additional brain areas, reflecting distinct modality-specific input gateways to the IPN. These areas involve, for the linguistic modality, the left inferior frontal gyrus (LIFG), and for the extralinguistic modality, the right inferior frontal gyrus (RIFG). Here, we tested the modality-specific gateway hypothesis, by using DCM to measure inter-regional functional integration dynamics between the IPN and LIFG/RIFG gateways. We found strong evidence of a well-defined effective connectivity architecture mediating the functional integration between the IPN and the inferior frontal cortices. The connectivity dynamics indicate a modality-specific propagation of stimulus information from LIFG to IPN for the linguistic modality, and from RIFG to IPN for the extralinguistic modality. Thus, we suggest a functional model in which the modality-specific gateways mediate the structural and semantic decoding of the stimuli, and allow for the modality-specific communicative information to be integrated in Theory of Mind inferences elaborated through the IPN.