Recent publications
Purpose
Radiomics-based machine learning (ML) models of amino acid positron emission tomography (PET) images have shown efficiency in glioma prediction tasks. However, their clinical impact on physician interpretation remains limited. This study investigated whether an explainable radiomics model modifies nuclear physicians’ assessment of glioma aggressiveness at diagnosis.
Methods
Patients underwent dynamic 6-[¹⁸F]fluoro-L-DOPA PET acquisition. With a 75%/25% split for training (n = 63) and test sets (n = 22), an ensemble ML model was trained using radiomics features extracted from static/dynamic parametric PET images to classify lesion aggressiveness. Three explainable ML methods—Local Interpretable Model-agnostic Explanations (LIME), Anchor, and SHapley Additive exPlanations (SHAP)—generated patient-specific explanations. Eighteen physicians from eight institutions evaluated the test samples. During the first phase, physicians analyzed the 22 cases exclusively through magnetic resonance and static/dynamic PET images, acquired within a maximum interval of 30 days. In the second phase, the same physicians reevaluated the same cases (n = 22), using all available data, including the radiomics model predictions and explanations.
Results
Eighty-five patients (54[39–62] years old, 41 women) were selected. In the second phase, physicians demonstrated a significant improvement in diagnostic accuracy compared to the first phase (0.775 [0.750–0.802] vs. 0.717 [0.694–0.737], p = 0.007). The explainable radiomics model augmented physician agreement, with a 22.72% increase in Fleiss’s kappa, and significantly enhanced physician confidence (p < 0.001). Among all physicians, Anchor and SHAP showed efficacy in 75% and 72% of cases, respectively, outperforming LIME (p ≤ 0.001).
Conclusions
Our results highlight the potential of an explainable radiomics model using amino acid PET scans as a diagnostic support to assist physicians in identifying glioma aggressiveness.
In primates, the presence of a face in a visual scene captures attention and rapidly directs the observer's gaze to the face, even when the face is not relevant to the task at hand. Here, we explored a neural circuit that might potentially play a causal role in this powerful behavior. In our previous research, two monkeys received microinfusions of muscimol, a γ-aminobutyric acid type A (GABAA)-receptor agonist, or saline (as a control condition) in separate sessions into individual or pairs of four inferotemporal face patches (middle and anterior lateral and fundal), as identified by an initial localizer experiment. Then, using fMRI, we measured the impact of each inactivation condition on responses in the other face patches relative to the control condition. In this study, we used the same method and measured the impact of each inactivation condition on responses in the FEF and the lateral intraparietal area, two regions associated with attentional processing, while face and nonface object stimuli were viewed. Our results revealed potential relationships between inferotemporal face patches and these two attention-related regions: The inactivation of the middle lateral and anterior fundal face patches had a pronounced impact on FEF, whereas the inactivation of the middle and anterior lateral face patches had a noticeable influence on LIP. Together, these initial exploratory findings document a circuit that potentially underlies the attentional capture of faces. Confirmation of the role of this circuit remains to be accomplished in the context of a paradigm that explicitly tests the attentional capture of faces.
Background
Cardiovascular risk factors represent an important health issue in older adults. Previous findings suggest that meditation training could have a positive impact on these risk factors. The objective of this study was to investigate the effects of an 18-month meditation-based intervention on cardiovascular health.
Methods
Age-Well was a randomized, controlled superiority trial with blinded end point assessment, including community-dwelling cognitively unimpaired adults 65 years and older enrolled between November 24, 2016, and March 5, 2018, in France. One hundred and thirty-four participants were included in this secondary analysis. Participants were randomly affected to an intervention group that received an 18-month meditation-based program or to comparison groups (active control group i.e. non-native language training or passive control group i.e. no intervention). The main outcome was change in the Framingham Risk Score (FRS); other outcomes were changes in cardiovascular and metabolic risk factors.
Results
There was no difference in FRS change after 18 months between trial arms (p = .38). When assessing individual cardiovascular or metabolic risk factors, meditation training was associated with a greater reduction in diastolic blood pressure than the comparison group in participants with intermediate to high cardiovascular risk (FRS > 10%) at baseline (p = .03).
Conclusion
An 18-month meditation training was not effective to increase overall cardiovascular health in older adults, but improved diastolic blood pressure in a subgroup analysis including at-risk participants. These results suggest a potential benefit of a long-term meditation intervention in older adults at-risk of cardiovascular diseases, and highlights the need for future research in more targeted populations.
Trial registration
ClinicalTrials.gov Identifier: NCT02977819.
Purpose
This systematic review covers the current stage of research on subtle cognitive impairment with connected speech. It aims at surveying the linguistic features in use to single out those that can best identify patients with mild neurocognitive disorders (mNCDs), whose cognitive changes remain underdiagnosed.
Method
We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and proposed a full definition of features for the analysis of speech features. Fifty-one studies met the inclusion criteria. Most of them focused on age-related progressive diseases and included fewer than 30 subjects.
Results
A total of 384 features labeled with 335 different names was retrieved, yielding various results in discriminating individuals with mNCDs from controls.
Conclusions
This finding highlights the need for harmonized labels to further investigate mNCDs with linguistic markers. We suggest two different ways of assessing a feature's reliability. We also point out potential methodological issues that remain to be resolved, along with recommendations for reproducible research in the field.
Social Facilitation/Inhibition (SFI) refers to how others' presence influences task performance positively or negatively. Our previous study revealed that peer presence modulated saccadic eye movements, a fundamental sensorimotor activity. Pro- and anti-saccades were either facilitated or inhibited depending on trial block complexity (Tricoche et al., 2020). In the present fMRI study, we adapted our paradigm to investigate the neural basis of SFI on saccades. Considering inter- and intra-individual variabilities, we evaluated the shared and distinct neural patterns between social facilitation and inhibition. We predicted an involvement of the saccade-related and attention networks, alongside the Theory-of-Mind (ToM) network, with opposite activity changes between facilitation and inhibition. Results confirmed peer presence modulation in fronto-parietal areas related to saccades and attention, in opposite directions for facilitation and inhibition. Additionally, the ventral attention network was modulated during inhibition. Default mode regions, including ToM areas, were also modulated. Finally, pupil size, often linked to arousal, increased with peers and correlated with dorsal attention regions and anterior insula activities. These results suggest that SFI engages task-specific and domain-general networks, modulated differently based on observed social effect. Attention network seemed to play a central role at both basic (linked to arousal or vigilance) and cognitive control levels.
The speed at which we move is linked to the speed at which we decide to make these movements. Yet, the principles guiding such relationship remain unclear: while some studies point towards a shared invigoration process boosting decision and movement speed jointly, others rather indicate a tradeoff between both levels of control, with slower movements accompanying faster decisions. Here, we aimed (1) at further investigating the existence of a shared invigoration process linking decision and movement and (2) at testing the hypothesis that such a link is masked when detrimental to the reward rate. To this aim, we tested 62 subjects who performed the tokens task in two experiments (separate sessions): Experiment 1 evaluated how changing decision speed affects movement speed while Experiment 2 assessed how changing movement speed affects decision speed. In the latter experiment, subjects were either encouraged to favor decision speed (fast decision group) or decision accuracy (slow decision group). Various mixed model analyses revealed a coregulation of decision (urgency) and movement speed in Experiment 1 and in the fast decision group of Experiment 2, but not in the slow decision group despite the fact that these same subjects displayed a coregulation effect in Experiment 1. Altogether, our findings support the idea that coregulation occurs as a default mode but that this form of control is diminished or supplanted by a tradeoff relationship, contingent on reward rate maximization. Drawing from these behavioral observations, we propose that multiple processes contribute to shaping the speed of decisions and movements.
The interaction of language with perception, action, and cognition has been a recurring theme across the cognitive sciences. Recently, research has emphasized the role of language not only as a communication device but also as a cognitive tool. The rise of large language models (LLMs) and their recent integration in embodied AI systems perceiving and acting in physical and social environments (robotics) is facing similar issues and has the potential to offer insights also into the relationship between language and human cognition. Here we chart parallel developments in these fields with the aim of fostering cross-talk and collaboration. First, we discuss work in psychology and neuroscience on language grounding and the effects of language on perception, action, and other cognitive processes. Next, we explore recent work in machine learning and robotics to design language-conditioned robots that comprehend and act on linguistic instructions, which provide new mechanistic insights on language effects. We conclude by arguing that these new parallel trends of research are finally able to capture the importance of language, in its experiential aspects that involve social interaction, thought, and behavior control.
When reproducing sounds over headphones, the simulated source can be externalized (i.e., perceived outside the head) or internalized (i.e., perceived within the head). Is it because it is perceived as more or less distant? To investigate this question, 18 participants evaluated distance and externalization for three types of sound (speech, piano, helicopter) in 27 conditions using nonindividualized stimuli. Distance and externalization ratings were significantly correlated across conditions and listeners, and when averaged across listeners or conditions. However, they were also decoupled in some circumstances: (1) Sound type had different effects on distance and externalization: the helicopter was evaluated as more distant, while speech was judged as less externalized. (2) Distance estimations increased with simulated distances even for stimuli judged as internalized. (3) Diotic reverberation influenced distance but not externalization. Overall, a source was not rated as externalized as soon as and only if its perceived distance exceeded a threshold (e.g., the head radius). These results suggest that distance and externalization are correlated but might not be aspects of a single perceptual continuum. In particular, a virtual source might be judged as both internalized and with a distance. Hence, it could be important to avoid using a scale related to distance when evaluating externalization.
Many recent studies indicate that control of decisions and actions is integrated during interactive behavior. Among these, several carried out in humans and monkeys conclude that there is a co-regulation of choices and movements. Another perspective, based on human data only, proposes a decoupled control of decision duration and movement speed, allowing for instance to trade decision duration for movement duration when time pressure increases. Crucially, it is not currently known whether this ability to flexibly dissociate decision duration from movement speed is specific to humans, whether it can vary depending on the context in which a task is performed, and whether it is stable over time. These are important questions to address, especially to rely on monkey electrophysiology to infer the neural mechanisms of decision-action coordination in humans. To do so, we trained two macaque monkeys in a perceptual decision-making task and analyzed data collected over multiple behavioral sessions. Our findings reveal a strong and complex relationship between decision duration and movement vigor. Decision duration and action duration can co-vary but also "compensate" each other. Such integrated but decoupled control of decisions and actions aligns with recent studies in humans, validating the monkey model in electrophysiology as a means of inferring neural mechanisms in humans. Crucially, we demonstrate for the first time that this control can evolve with experience, in an adapted manner. Together, the present findings contribute to deepening our understanding of the integrated control of decisions and actions during interactive behavior.
Background
Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without cognitive impairment.
Methods
A total of 137 adults age ≥65 years were randomized to one of the 3 groups (meditation training, non-native language training, or passive control). We evaluated the 50th and 20th percentile TL and the percentage of critically short telomeres (<3 kbp) in peripheral blood mononuclear cells.
Results
Mixed model analysis showed a time effect indicating a general decrease on the 50th percentile TL (F = 80.72, padjusted < .001), without a significant group effect or time × group interaction. No significant effect was detected in the 20th percentile TL or the percentage of critically short telomeres. Secondary analysis showed that only in the meditation training group 1) the 50th percentile TL positively correlated with class attendance time (r = 0.45, padjusted < .011), 2) the 50th and 20th percentile TL positively correlated with responsiveness to the intervention, evaluated through a composite score (r = 0.46, padjusted < .010 and r = 0.41, padjusted = .029, respectively), and 3) lower scores on a measure of the personality trait “openness to experience” correlated with a lower percentage of critically short telomeres after the intervention (r = 0.44, padjusted = .015).
Conclusions
In older adults, we found no evidence for a main effect of an 18-month meditation training program on TL compared with the control groups. Our findings highlight the importance of considering the impact of moderating factors when measuring the effectiveness of meditation-based trainings.
Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.
Adaptation of reactive saccades (RS), made toward the sudden appearance of stimuli in our environment, is a plastic mechanism thought to occur at the motor level of saccade generation. As saccadic oculomotor commands integrate multisensory information in the parietal cortex and superior colliculus, adaptation of RS should occur not only towards visual but also tactile targets. In addition, saccadic adaptation in one modality (vision or touch) should transfer cross-modally. To test these predictions, we used the double-step target paradigm to adapt rightward saccades made at two different eccentricities toward the participants' index and middle fingers, identified either visually (Experiment1) or tactually (Experiment2). In each experiment, the rate of adaptation induced for the adapted modality and the rate of adaptation transfer to the non-adapted modality were compared to that measured in a control (no adaptation) session. Results revealed that touch-triggered RS can be adapted as well as visually triggered ones. Moreover, the transfer pattern was asymmetric: visual saccadic adaptation transferred fully to tactile saccades, whereas tactile saccadic adaptation, despite full generalization to non-adapted fingers, transferred only partially to visual saccades. These findings disclose that in the case of tactile saccades, adaptation can be elicited in the absence of post-saccadic visual feedback. In addition, the asymmetric adaptation transfer across sensory modalities suggests that the adaptation locus for tactile saccades may occur in part upstream of the final motor pathway common to all saccades. These findings bring new insights both on the functional loci(us) and on the error signals of RS adaptation.
Brain tissue oxygen pressure (PbtO2) monitoring is important to understand brain metabolism at rest or during neuronal activation. Electrochemistry provides high spatial and temporal resolution to achieve PbtO2 monitoring, especially platinum (so-called Clark electrodes) and carbon fiber microelectrodes (CFMEs). However, a major problem with in vivo PbtO2 recordings is a significant loss of sensitivity due to sensor fouling in the living brain tissue. Here, we tested a polyphenylenediamine-polyurethane (PPD-PU) coating to minimize electrode fouling in vivo and improve the stability of PbtO2 recordings. PPD and PU coatings were deposited on CFMEs (7 μm diameter, 100 μm long, 4400 μm2) and displayed less fouling in vivo than bare CFMEs, or CFMEs coated with PPD only. Oxygen reduction started around -300 mV vs Ag/AgCl and PPD-PU deposition increased microelectrode diameter by 1-2 μm. Carbon fiber microelectrodes coated with PPD-PU were used for 2.5-5 h of PbtO2 monitoring in anesthetized rats and there was no significant change in O2 sensitivity before and after in vivo implantation. These results indicate that PbtO2 monitoring can be achieved reliably using PPD-PU coating on carbon fiber microelectrodes, preventing electrode fouling in vivo, and providing an inexpensive and minimally invasive tool to study brain oxygen metabolism.
Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.
Objective
Evidence suggests that the most promising results in interictal localization of the epileptogenic zone (EZ) are achieved by a combination of multiple stereo‐electroencephalography (SEEG) biomarkers in machine learning models. These biomarkers usually include SEEG features calculated in standard frequency bands, but also high‐frequency (HF) bands. Unfortunately, HF features require extra effort to record, store, and process. Here we investigate the added value of these HF features for EZ localization and postsurgical outcome prediction.
Methods
In 50 patients we analyzed 30 min of SEEG recorded during non–rapid eye movement sleep and tested a logistic regression model with three different sets of features. The first model used broadband features (1–500 Hz); the second model used low‐frequency features up to 45 Hz; and the third model used HF features above 65 Hz. The EZ localization by each model was evaluated by various metrics including the area under the precision‐recall curve (AUPRC) and the positive predictive value (PPV). The differences between the models were tested by the Wilcoxon signed‐rank tests and Cliff's Delta effect size. The differences in outcome predictions based on PPV values were further tested by the McNemar test.
Results
The AUPRC score of the random chance classifier was .098. The models (broad‐band, low‐frequency, high‐frequency) achieved median AUPRCs of .608, .582, and .522, respectively, and correctly predicted outcomes in 38, 38, and 33 patients. There were no statistically significant differences in AUPRC or any other metric between the three models. Adding HF features to the model did not have any additional contribution.
Significance
Low‐frequency features are sufficient for correct localization of the EZ and outcome prediction with no additional value when considering HF features. This finding allows significant simplification of the feature calculation process and opens the possibility of using these models in SEEG recordings with lower sampling rates, as commonly performed in clinical routines.
NLX-112 (i.e., F13640, befiradol) exhibits nanomolar affinity, exceptional selectivity and full agonist efficacy at serotonin 5-HT1A receptors. NLX-112 shows efficacy in rat, marmoset and macaque models of L-DOPA induced dyskinesia (LID) in Parkinson’s disease and has shown clinical efficacy in a Phase 2a proof-of-concept study for this indication. Here we investigated, in rats, its pharmacodynamic, pharmacokinetic (PK) and brain 5-HT1A receptor occupancy profiles, and its PK properties in the absence and presence of L-DOPA. Total and free NLX-112 exposure in plasma, CSF and striatal ECF was dose-proportional over the range tested (0.04, 0.16 and 0.63 mg/kg i.p.). NLX-112 exposure increased rapidly (Tmax 0.25–0.5h) and exhibited approximately threefold longer half-life in brain than in plasma (1.1 and 3.6h, respectively). At a pharmacologically relevant dose of 0.16 mg/kg i.p., previously shown to elicit anti-LID activity in parkinsonian rats, brain concentration of NLX-112 was 51–63 ng/g from 0.15 to 1h. In microPET imaging experiments, NLX-112 showed dose-dependent reduction of ¹⁸F-F13640 (i.e., ¹⁸F-NLX-112) brain 5-HT1A receptor labeling in cingulate cortex and striatum, regions associated with motor control and mood, with almost complete inhibition of labeling at the dose of 0.63 mg/kg i.p.. Co-administration of L-DOPA (6 mg/kg s.c., a dose used to elicit LID in parkinsonian rats) together with NLX-112 (0.16 mg/kg i.p.) did not modify PK parameters in rat plasma and brain of either NLX-112 or L-DOPA. Here, we demonstrate that NLX-112’s profile is compatible with ‘druggable’ parameters for CNS indications, and the results provide measures of brain concentrations and 5-HT1A receptor binding parameters relevant to the anti-dyskinetic activity of the compound.
Implicit sensorimotor adaptation keeps our movements well-calibrated amid changes in the body and environment. We have recently postulated that implicit adaptation is driven by a perceptual error: the difference between the desired and perceived movement outcome. According to this perceptual re-alignment model, implicit adaptation ceases when the perceived movement outcome - a multimodal percept determined by a prior belief conveying the intended action, the motor command, and feedback from proprioception and vision - is aligned with the desired movement outcome. Here, we examined the role of proprioception in implicit motor adaptation and perceived movement outcome by examining individuals who experience deafferentation (i.e., individuals with impaired proprioception and touch). We used a modified visuomotor rotation task designed to isolate implicit adaptation and probe perceived movement outcome throughout the experiment. Surprisingly, both implicit adaptation and perceived movement outcome were minimally impacted by chronic deafferentation, posing a challenge to the perceptual re-alignment model of implicit adaptation.
Background
Perceptual and speech production abilities of children with cochlear implants (CIs) are usually tested by word and sentence repetition or naming tests. However, these tests are quite far apart from daily life linguistic contexts.
Aim
Here, we describe a way of investigating the link between language comprehension and anticipatory verbal behaviour promoting the use of more complex listening situations.
Methods and Procedure
The setup consists in watching the audio‐visual dialogue of two actors. Children's gaze switches from one speaker to the other serve as a proxy of their prediction abilities. Moreover, to better understand the basis and the impact of anticipatory behaviour, we also measured children's ability to understand the dialogue content, their speech perception and memory skills as well as their rhythmic skills, that also require temporal predictions. Importantly, we compared children with CI performances with those of an age‐matched group of children with normal hearing (NH).
Outcomes and Results
While children with CI revealed poorer speech perception and verbal working memory abilities than NH children, there was no difference in gaze anticipatory behaviour. Interestingly, in children with CI only, we found a significant correlation between dialogue comprehension, perceptual skills and gaze anticipatory behaviour.
Conclusion
Our results extend to a dialogue context of previous findings showing an absence of predictive deficits in children with CI. The current design seems an interesting avenue to provide an accurate and objective estimate of anticipatory language behaviour in a more ecological linguistic context also with young children.
WHAT THIS PAPER ADDS
What is already known on the subject
Children with cochlear implants seem to have difficulties extracting structure from and learning sequential input patterns, possibly due to signal degradation and auditory deprivation in the first years of life. They also seem to have a reduced use of contextual information and slow language processing among children with hearing loss.
What this paper adds to existing knowledge
Here we show that when adopting a rather complex linguistic context such as watching a dialogue of two individuals, children with cochlear implants are able to use the speech and language structure to anticipate gaze switches to the upcoming speaker.
What are the clinical implications of this work?
The present design seems an interesting avenue to provide an accurate and objective estimate of anticipatory behaviour in a more ecological and dynamic linguistic context. Importantly, this measure is implicit and it has been previously used with very young (normal‐hearing) children, showing that they spontaneously make anticipatory gaze switches by age two. Thus, this approach may be of interest to refine the speech comprehension assessment at a rather early age after cochlear implantation where explicit behavioural tests are not always reliable and sensitive.
Human nonverbal vocalizations such as screams and cries often reflect their evolved functions. Although the universality of these putatively primordial vocal signals and their phylogenetic roots in animal calls suggest a strong reflexive foundation, many of the emotional vocalizations that we humans produce are under our voluntary control. This suggests that, like speech, volitional vocalizations may require auditory input to develop typically. Here, we acoustically analyzed hundreds of volitional vocalizations produced by profoundly deaf adults and typically-hearing controls. We show that deaf adults produce unconventional and homogenous vocalizations of aggression and pain that are unusually high-pitched, unarticulated, and with extremely few harsh-sounding nonlinear phenomena compared to controls. In contrast, fear vocalizations of deaf adults are relatively acoustically typical. In four lab experiments involving a range of perception tasks with 444 participants, listeners were less accurate in identifying the intended emotions of vocalizations produced by deaf vocalizers than by controls, perceived their vocalizations as less authentic, and reliably detected deafness. Vocalizations of congenitally deaf adults with zero auditory experience were most atypical, suggesting additive effects of auditory deprivation. Vocal learning in humans may thus be required not only for speech, but also to acquire the full repertoire of volitional non-linguistic vocalizations.
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