Disrupted intrinsic connectivity links to language and social deficits in toddlers with autism

Social and language abilities are closely intertwined during early development. Yet, it is still unknown how neural features underlying early social and language deficits are linked in toddlers with autism spectrum disorders (ASD). We examined functional connectivity of left and right temporal language regions and its correlations with language and social abilities in a cohort of 1-4 years old toddlers (52 ASD/34 non-ASD). Further, ASD toddlers were stratified into those who strongly prefer social visual stimuli (ASDSoc) vs. those who do not (ASDnonSoc) based on performance on an eye-tracking paradigm. In non-ASD toddlers, connectivity between temporal regions and other language- and social-related cortical regions was significantly correlated with language, communication, and social scores. Conversely, ASD toddlers showed atypical correlations between temporal-visual cortex (cuneus) connectivity and communication ability. This temporal-visual connectivity was also correlated with social visual attention in ASDnonSoc but not in ASDSoc toddlers. These findings suggest language- and social-related functional connectivity was not correlated with language and social functions in ASD toddlers. Abnormal engagement of temporal-visual cortex connectivity may be an early-age signature of ASD and may help explain why interventions targeting social skills and language are so challenging, particularly in those with poor social engagement.

Clinical Speech fMRI in Children and Adolescents

Purpose In patients with drug-resistant focal epilepsy, surgical resection is often the only treatment option to achieve long-term seizure control. Prior to brain surgery involving potential language areas, identification of hemispheric language dominance is crucial. Our group developed and validated a functional magnetic resonance imaging (fMRI) battery of four pediatric language tasks. The present study aimed at optimizing fMRI data acquisition and analysis using these tasks. Methods We retrospectively analyzed speech fMRI examinations of 114 neuropediatric patients (age range 5.8–17.8 years) who were examined prior to possible epilepsy surgery. In order to evaluate hemispheric language dominance, 1–4 language tasks (vowel identification task VIT, word-chain task WCT, beep-story task BST, synonym task SYT) were measured. Results Language dominance was classified using fMRI activation in the 13 validly lateralizing ROIs (VLR) in frontal, temporal and parietal lobes and cerebellum of the recent validation study from our group: 47/114 patients were classified as left-dominant, 34/114 as bilateral and 6/114 as right-dominant. In an attempt to enlarge the set of VLR, we then compared for each task agreement of these ROI activations with the classified language dominance. We found four additional task-specific ROIs showing concordant activation and activation in ≥ 10 sessions, which we termed validly lateralizing (VLRnew). The new VLRs were: for VIT the temporal language area and for SYT the middle frontal gyrus, the intraparietal sulcus and cerebellum. Finally, in order to find the optimal sequence of measuring the different tasks, we analyzed the success rates of single tasks and all possible task combinations. The sequence 1) VIT 2) WCT 3) BST 4) SYT was identified as the optimal sequence, yielding the highest chance to obtain reliable results even when the fMRI examination has to be stopped, e.g., due to lack of cooperation. Conclusion Our suggested task order together with the enlarged set of VLRnew may contribute to optimize pediatric speech fMRI in a clinical setting.

The universal language network: A cross-linguistic investigation spanning 45 languages and 11 language families.

To understand the architecture of human language, it is critical to examine diverse languages; yet most cognitive neuroscience research has focused on a handful of primarily Indo-European languages. Here, we report a large-scale investigation of the fronto-temporal language network across 45 languages and establish the cross-linguistic generality of its key functional properties, including general topography, left-lateralization, strong functional integration among its brain regions, and functional selectivity for language processing.

Frontal language areas do not emerge in the absence of temporal language areas: A case study of an individual born without a left temporal lobe

High-level language processing is supported by a left-lateralized fronto-temporal brain network. How this network emerges ontogenetically remains debated. Given that frontal cortex in general exhibits protracted development, frontal language areas presumably emerge later and/or mature more slowly than temporal language areas. But are temporal areas necessary for the development of the language areas in the frontal lobe, or do frontal language areas instead emerge independently? We shed light on this question through a case study of an individual (EG) born without a left temporal lobe. We use fMRI methods that have been previously extensively validated for their ability to elicit robust language responses at the individual-subject level. As expected in cases of early left hemisphere (LH) damage, we find that EG has a fully functional language network in her right hemisphere (RH) and performs within the normal range on standardized language assessments. However, her RH frontal language areas have no corresponding LH homotopic areas: no reliable response to language is detected on the lateral surface of EG's left frontal lobe. However, another network implicated in high-level cognition - the domain-general multiple demand, MD, network - is robustly present in both right and left frontal lobes, suggesting that EG's left frontal cortex is capable of supporting non-linguistic cognitive functions. The existence of temporal language areas therefore appears to be a prerequisite for the emergence of the language areas in the frontal lobe.

Language Mapping Using Stereo Electroencephalography: A Review and Expert Opinion

Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.

Mapping Complex Brain Torque Components and Their Genetic and Phenomic Architecture in 24,112 healthy individuals

The mechanisms determining the development and individual variability of brain torque (BT) remain unclear. Here, all relevant components of BT were analyzed using neuroimaging data of up to 24,112 individuals from 6 cohorts. Our large-scale data confirmed the population-level predominance of the typical anticlockwise torque and suggested a “first attenuating, then enlarging” dynamic across the lifespan primarily for frontal, occipital and perisylvian BT features. Sex/handedness differences in BT were found and were related to cognitive sex/handedness differences in verbal-numerical reasoning. We observed differential heritability of up to 56% for BT, especially in temporal language areas, and identified numerous genome- and phenome-wide significant associations pointing to neurodevelopment, cognitive functions, lifestyle, neurological and psychiatric disorders, sociodemographic, cardiovascular and anthropometric traits. This study provides a comprehensive description of BT and insights into biological and other factors that may contribute to the development and individual variations of BT.

Distinct Neural Correlates of Linguistic and Non-Linguistic Demand

In this study, we investigated how the brain responds to task difficulty in linguistic and non-linguistic contexts. This is important for the interpretation of functional imaging studies of neuroplasticity in post-stroke aphasia, because of the inherent difficulty of matching or controlling task difficulty in studies with neurological populations. Twenty neurologically normal individuals were scanned with fMRI as they performed a linguistic task and a non-linguistic task, each of which had two levels of difficulty. Critically, the tasks were matched across domains (linguistic, non-linguistic) for accuracy and reaction time, such that the differences between the easy and difficult conditions were equivalent across domains. We found that non-linguistic demand modulated the same set of multiple demand (MD) regions that have been identified in many prior studies. In contrast, linguistic demand modulated MD regions to a much lesser extent, especially nodes belonging to the dorsal attention network. Linguistic demand modulated a subset of language regions, with the left inferior frontal gyrus most strongly modulated. The right hemisphere region homotopic to Broca’s area was also modulated by linguistic but not non-linguistic demand. When linguistic demand was mapped relative to non-linguistic demand, we also observed domain by difficulty interactions in temporal language regions as well as a widespread bilateral semantic network. In sum, linguistic and non-linguistic demand have strikingly different neural correlates. These findings can be used to better interpret studies of patients recovering from aphasia. Some reported activations in these studies may reflect task performance differences, while others can be more confidently attributed to neuroplasticity.