Exploring oculomotor functions in a pilot study with healthy controls: Insights from eye-tracking and fMRI.

Eye-tracking techniques have gained widespread application in various fields including research on the visual system, neurosciences, psychology, and human-computer interaction, with emerging clinical implications. In this preliminary phase of our study, we introduce a pilot test of innovative virtual reality technology designed for tracking head and eye movements among healthy individuals. This tool was developed to assess the presence of mild traumatic brain injury (mTBI), given the frequent association of oculomotor function deficits with such injuries. Alongside eye-tracking, we also integrated fMRI due to the complementary nature of these techniques, offering insights into both neural activation patterns and behavioural responses, thereby providing a comprehensive understanding of oculomotor function. We used fMRI with tasks evaluating oculomotor functions: Smooth Pursuit (SP), Saccades, Anti-Saccades, and Optokinetic Nystagmus (OKN). Prior to the scanning, the testing with a system of VR goggles with integrated eye and head tracking was used where subjects performed the same tasks as those used in fMRI. 31 healthy adult controls (HCs) were tested with the purpose of identifying brain regions associated with these tasks and collecting preliminary norms for later comparison with concussed subjects. HCs' fMRI results showed following peak activation regions: SP-cuneus, superior parietal lobule, paracentral lobule, inferior parietal lobule (IPL), cerebellartonsil (CT); Saccades-middle frontal gyrus (MFG), postcentral gyrus, medial frontal gyrus; Anti-saccades-precuneus, IPL, MFG; OKN-middle temporal gyrus, ACC, postcentral gyrus, MFG, CT. These results demonstrated brain regions associated with the performance on oculomotor tasks in healthy controls and most of the highlighted areas are corresponding with those affected in concussion. This suggests that the involvement of brain areas susceptible to mTBI in implementing oculomotor evaluation, taken together with commonly reported oculomotor difficulties post-concussion, may lead to finding objective biomarkers using eye-tracking tasks.

Restricted language access during childhood affects adult brain structure in selective language regions.

Due to the ubiquitous nature of language in the environment of infants, how it affects the anatomical structure of the brain language system over the lifespan is not well understood. In this study, we investigated the effects of early language experience on the adult brain by examining anatomical features of individuals born deaf with typical or restricted language experience in early childhood. Twenty-two deaf adults whose primary language was American Sign Language and were first immersed in it at ages ranging from birth to 14 y participated. The control group was 21 hearing non-signers. We acquired T1-weighted magnetic resonance images and used FreeSurfer [B. Fischl, Neuroimage 62, 774-781(2012)] to reconstruct the brain surface. Using an a priori regions of interest (ROI) approach, we identified 17 language and 19 somatomotor ROIs in each hemisphere from the Human Connectome Project parcellation map [M. F. Glasser et al., Nature 536, 171-178 (2016)]. Restricted language experience in early childhood was associated with negative changes in adjusted grey matter volume and/or cortical thickness in bilateral fronto-temporal regions. No evidence of anatomical differences was observed in any of these regions when deaf signers with infant sign language experience were compared with hearing speakers with infant spoken language experience, showing that the effects of early language experience on the brain language system are supramodal.

Bilingual language experience and the neural underpinnings of working memory.

A longstanding question in cognitive neuroscience and in the bilingualism literature is how early language experience influences brain development and cognitive outcomes, and whether these effects are global or specific to language-related processes. The current investigation examined the effect of the timing of language learning on the performance and neural correlates of phonological and non-verbal working memory, subcomponents of executive function. Three groups of bilinguals, who varied in terms of the timing of second language learning (i.e., simultaneous bilinguals learned their two languages from birth; early and late bilinguals who learned their second language before or after 5 years of age, respectively), performed phonological and non-verbal working memory tasks in the magnetic resonance imaging scanner. Results showed that there were no group differences in performance on either of the tasks, or in the neural correlates of performance of the non-verbal task. However, critically, we showed that despite similar behavioural performance, the groups differed in the patterns of neural recruitment during performance of the phonological working memory task. The pattern of group differences was non-linear, demonstrating similar neural recruitment for simultaneous and late bilinguals that differed from early bilinguals. Findings from the current study suggest a dynamic mapping between the brain and cognition, contributing to our current understanding of the effect of the timing of language learning on cognitive processes and demonstrating a specific effect on language-related executive function.

Atypical resting state functional connectivity in mild traumatic brain injury.

OBJECTIVES: This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode network [DMN], salience network [SN], and task-positive network [TPN]) in individuals who had sustained a mild traumatic brain injury (mTBI). METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 27 mTBI patients with persistent postconcussive symptoms, along with 26 age- and sex-matched controls. These individuals were recruited from a Level-1 trauma center, at least 3 months after a traumatic episode. IFCNs were established based on seed-to-voxel, region-of-interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and postconcussive symptoms. RESULTS: Seed-to-voxel analysis of rs-fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo- and hyperconnectivity dependent on seed location. Within network hypoconnectivity was observed in the visual network also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioral symptoms score was also found. CONCLUSIONS: Our findings indicate that rs-fMRI may be of use clinically in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent postconcussive symptoms months after injury, who hope to resume activity.

Prosopagnosia seizure semiology in a 10-year-old boy: a functional neuroimaging study.

We illustrate a case of post-traumatic recurrent transient prosopagnosia in a paediatric patient with a right posterior inferior temporal gyrus haemorrhage seen on imaging and interictal electroencephalogram abnormalities in the right posterior quadrant. Face recognition area mapping with magnetoencephalography (MEG) and functional MRI (fMRI) was performed to clarify the relationship between the lesion and his prosopagnosia, which showed activation of the right fusiform gyrus that colocalised with the lesion. Lesions adjacent to the right fusiform gyrus can result in seizures presenting as transient prosopagnosia. MEG and fMRI can help to attribute this unique semiology to the lesion.

Language learning experience and mastering the challenges of perceiving speech in noise.

Given the ubiquity of noisy environments and increasing globalization, the necessity to perceive speech in noise in a non-native language is common and necessary for successful communication. In the current investigation, bilingual individuals who learned their non-native language at different ages underwent magnetic resonance imaging while listening to sentences in both of their languages, in quiet and in noise. Sentence context was varied such that the final word could be of high or low predictability. Results show that early non-native language learning is associated with superior ability to benefit from contextual information behaviourally, and a pattern of neural recruitment in the left inferior frontal gyrus that suggests easier processing when perceiving non-native speech in noise. These findings have implications for our understanding of speech processing in non-optimal listening conditions and shed light on how individuals navigate every day complex communicative environments, in a native and non-native language.

Impact of non-invasive brain stimulation on transcallosal modulation in mild traumatic brain injury: a multimodal pilot investigation.

Background: We combined performance on working memory (WM) tasks with diffusion (dMRI) and functional (fMRI) magnetic resonance imaging in young adults who had suffered a concussion to better understand the inter-hemispheric effects of unilateral repetitive transcranial magnetic stimulation (rTMS). Methods: The article is presenting pilot data on 8 symptomatic patients with persistent post-concussion symptoms for over 6 months. They received 20 sessions of rTMS over the left dorsolateral prefrontal cortex. Fractional anisotropy and mean diffusivity of the corpus callosum (CC) and fMRI measurement of blood-oxygen-level dependent signal changes during WM tasks were carried out before and after rTMS stimulation. Results: After participants had completed the rTMS sessions, we observed three main results: (1) bilateralization of activation within the WM network; (2) shift from transcallosal inhibition to transcallosal activation of the right-sided WM network via the anterior callosal fibres; and (3) shift from transcallosal activation to transcallosal inhibition of the right-sided WM network via the posterior parts of the CC. More nuanced patterns of transcallosal mediation in the region of the right-sided WM network were observed via the medial part of the CC. Conclusion: Our preliminary results encourage trends of further research supporting the use of rTMS to restore inter-hemispheric balance within the bilateral WM network in young adults with a history of concussion.

Brain functional organization and structure in patients with arteriovenous malformations.

PURPOSE: Developmental in nature, brain arteriovenous malformations (AVM) have the potential to affect whole brain organization. Here we investigated the impact of AVM on functional and structural brain organization using resting-state functional MRI (rsfMRI) and cortical thickness measures. METHODS: We investigated brain functional organization and structure using rsfMRI in conjunction with cortical thickness analyses in 23 patients with cerebral arteriovenous malformations (AVMs) and 20 healthy control subjects. RESULTS: Healthy controls showed the expected anti-correlation between activity in the default mode network (DMN) and frontal areas that are part of the attentional control network. By contrast, patients demonstrated a disruption of this anti-correlation. Disruptions to this anti-correlation were even observed in a subgroup of patients with lesions remote from the main nodes of the DMN and were unrelated to differences in perfusion. Functional connectivity differences were accompanied by reduced cortical thickness in frontal attentional areas in patients compared to the controls. CONCLUSIONS: These results contribute to the discussion that AVMs affect whole brain networks and not simply the area surrounding the lesion.

Evaluating task-based brain network activity in pediatric subjects with an mTBI: mechanisms of functional compensation are symptom-level dependent.

The diagnosis of a mild traumatic brain injury (mTBI) places large emphasis on patient-reported symptoms which has restricted our ability to evaluate patients. Task-based functional magnetic resonance imaging has the potential to act as an objective measurement of abnormal brain activity and inform clinical decision-making; however, there is little research evaluating pediatric subjects as a function of mTBI-related symptoms. The objective of this study was to evaluate the extent to which brain activity during a spatial navigation task is different between children with mTBI and a group of healthy controls (HCs) based on symptom reporting. A group of patients with mTBI (n = 27) were divided into low- and high-symptom cohorts and compared with HCs (n = 27) on a task that required participants to locate specific landmarks. No difference was found in the level of symptoms reported between patients with low-symptom participants and HCs despite the low-symptom group showing increased activity within the frontal and occipital cortices. In participants with high-symptoms, an increase in the number of reported symptoms was found relative to HCs alongside an increase in the number of active brain regions. Findings suggest that persons with an mTBI may display unique symptom-dependent patterns of altered task-related brain activity.

Noninvasive tongue stimulation combined with intensive cognitive and physical rehabilitation induces neuroplastic changes in patients with multiple sclerosis: A multimodal neuroimaging study.

BACKGROUND: Multiple sclerosis (MS) patients have central nervous system (CNS) lesions that may impede cognitive and sensorimotor function. Few rehabilitative therapies are available. OBJECTIVES: The objective of this paper is to study effects of noninvasive tongue stimulation using the Portable Neuromodulation Stimulator (PoNS™) combined with intensive cognitive and physical rehabilitation on working memory, gait, balance and concomitant changes in the brain. METHODS: Fourteen MS patients, seven each in an active and a sham stimulation group, participated. Participants received intensive physical therapy and working memory training for 14 weeks. Functional magnetic resonance imaging (fMRI) using motor imagery and working-memory tasks were completed prior to and following therapy, as were sensory organization tests (SOT), motor performance measures, and neuropsychological assessment. RESULTS: On the SOT, the active group showed significant improvement from baseline. fMRI revealed significant blood oxygen level-dependent signal changes in the left primary motor cortex for the Active Group, while the sham group had increased activity in bilateral premotor cortices. All individuals improved on working-memory tasks, but only the active group showed increased dorsolateral prefrontal cortex activity. CONCLUSIONS: In this cohort of MS patients, the results suggest that PoNS stimulation can enhance motor performance and working memory while also driving neuroplasticity. Further studies are warranted to explore these findings.

Role of advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion: a systematic review.

OBJECTIVE: To conduct a systematic review of published literature on advanced neuroimaging, fluid biomarkers and genetic testing in the assessment of sport-related concussion (SRC). DATA SOURCES: Computerised searches of Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus and Cochrane Library from 1 January 2000 to 31 December 2016 were done. There were 3222 articles identified. STUDY SELECTION: In addition to medical subject heading terms, a study was included if (1) published in English, (2) represented original research, (3) involved human research, (4) pertained to SRC and (5) involved data from neuroimaging, fluid biomarkers or genetic testing collected within 6 months of injury. Ninety-eight studies qualified for review (76 neuroimaging, 16 biomarkers and 6 genetic testing). DATA EXTRACTION: Separate reviews were conducted for neuroimaging, biomarkers and genetic testing. A standardised data extraction tool was used to document study design, population, tests employed and key findings. Reviewers used a modified quality assessment of studies of diagnostic accuracy studies (QUADAS-2) tool to rate the risk of bias, and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to rate the overall level of evidence for each search. DATA SYNTHESIS: Results from the three respective reviews are compiled in separate tables and an interpretive summary of the findings is provided. CONCLUSIONS: Advanced neuroimaging, fluid biomarkers and genetic testing are important research tools, but require further validation to determine their ultimate clinical utility in the evaluation of SRC. Future research efforts should address current gaps that limit clinical translation. Ultimately, research on neurobiological and genetic aspects of SRC is predicted to have major translational significance to evidence-based approaches to clinical management of SRC, much like applied clinical research has had over the past 20 years.

Cortical Thickness Changes and Their Relationship to Dual-Task Performance following Mild Traumatic Brain Injury in Youth.

Mild traumatic brain injury (mTBI) is common in youth, especially in those who participate in sport. Recent investigations from our group have shown that asymptomatic children and adolescents with mTBI continue to exhibit alterations in neural activity and cognitive performance compared with those without a history of mTBI. This is an intriguing finding, given that current return-to-learn and return-to-play protocols rely predominately on subjective symptom reports, which may not be sensitive enough to detect subtle injury-related changes. As a result, youth may be at greater risk for re-injury and long-term consequences if they are cleared for activity while their brains continue to be compromised. It is currently unknown whether mTBI also affects brain microstructure in the developing brain, particularly cortical thickness, and whether such changes are also related to cognitive performance. The present study examined cortical thickness in 13 asymptomatic youth (10-14 years old) who had sustained an mTBI 3-8 months prior to testing compared with 14 age-matched typically developing controls. Cortical thickness was also examined in relation to working memory performance during single and dual task paradigms. The results show that youth who had sustained an mTBI had thinner cortices in the left dorsolateral prefrontal region and right anterior and posterior inferior parietal lobes. Additionally, cortical thinning was associated with slower reaction time during the dual-task condition in the injured youth only. The results also point to a possible relationship between functional and structural alterations as a result of mTBI in youth, and lend evidence for neural changes beyond symptom resolution.

The role of the left inferior parietal lobule in second language learning: An intensive language training fMRI study.

Research to date suggests that second language acquisition results in functional and structural changes in the bilingual brain, however, in what way and how quickly these changes occur remains unclear. To address these questions, we studied fourteen English-speaking monolingual adults enrolled in a 12-week intensive French language-training program in Montreal. Using functional MRI, we investigated the neural changes associated with new language acquisition. The participants were scanned before the start of the immersion program and at the end of the 12 weeks. The fMRI scan aimed to investigate the brain regions recruited in a sentence reading task both in English, their first language (L1), and in French, their second language (L2). For the L1, fMRI patterns did not change from Time 1 to Time 2, while for the L2, the brain response changed between Time 1 and Time 2 in language-related areas. Of note, for the L2, there was higher activation at Time 2 compared to Time 1 in the left inferior parietal lobule (IPL) including the supramarginal gyrus. At Time 2 this higher activation in the IPL correlated with faster L2 reading speed. Moreover, higher activation in the left IPL at Time 1 predicted improvement in L2 reading speed from Time 1 to Time 2. Our results suggest that learning-induced plasticity occurred as early as 12 weeks into immersive second-language training, and that the IPL appears to play a special role in language learning.

Microstructural Integrity of Hippocampal Subregions Is Impaired after Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) affects a large number of individuals and diffusion tensor imaging can be used to investigate microstructural integrity of brain tissue after mTBI. However, results have varied considerably between studies and gray matter (GM) integrity has been largely neglected in these investigations. Given impaired working memory processing after mTBI and its possible association with Alzheimer's disease, we investigated hippocampal integrity and parcellated this structure into five subregions: subiculum, cornu ammonis (CA) 1, CA 2/3, CA 4/dentate gyrus, and stratum radiatum/lacunosum-moleculare. We also employed shape analysis of bilateral hippocampi to explore whether morphological changes had occurred due to the traumatic injury and conducted neuropsychological memory tests. The sample comprised 15 subjects with mTBI (18-55 years, nine female) and 13 age- and sex-matched healthy control subjects (19-57 years, nine female). Voxelwise analyses showed significantly increased mean diffusivity in patients, compared with controls, in the right hippocampus and three of its five subregions (family-wise error corrected p < 0.05). Additionally, results from probabilistic tractography indicated impaired CA 1 connectivity after mTBI (Benjamini-Hochberg false discovery rate [FDR] corrected p < 0.05). Shape of bilateral hippocampi did not significantly differ between groups (Benjamini-Hochberg FDR corrected p > 0.05). Subjects with mTBI reported more symptoms and performed worse in a non-standard verbal working memory task. Based on these preliminary findings, we were able to demonstrate altered diffusivity of hippocampal subregions following mTBI, indicating impaired GM microstructural integrity. These differences highlight the potential of diffusion imaging for investigation of subtle yet relevant changes in GM microstructure not detected otherwise following mTBI.

The impact of symptomatic mild traumatic brain injury on complex everyday activities and the link with alterations in cerebral functioning: Exploratory case studies.

The objective of the study was to explore the neurophysiological correlates of altered functional independence using functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) after a mild traumatic brain injury (mTBI). The participants consisted of three individuals with symptomatic mTBI (3.9 ± 3.6 months post-mTBI) and 12 healthy controls. The main measures used were the Instrumental Activities of Daily Living (IADL) Profile observation-based assessment; a visual externally ordered working memory task combined to event-related potentials (ERP) and fMRI recordings; neuropsychological tests; post-concussion symptoms questionnaires; and the Activities of Daily Living (ADL) Profile interview. Compared to normal controls, all three patients had difficulty with a real-world complex budgeting activity due to deficits in planning, ineffective strategy use and/or a prolonged time to detect and correct errors. Reduced activations in the right mid-dorsolateral prefrontal cortex on fMRI as well as abnormal frontal or parietal components of the ERP occurred alongside these deficits. Results of this exploratory study suggest that reduced independence in complex everyday activities in symptomatic mTBI may be at least partly explained by a decrease in brain activation in the prefrontal cortex, abnormal ERP, or slower reaction times on working memory tasks. The study presents an initial attempt at combining research in neuroscience with ecological real-world evaluation research to further our understanding of the difficulties in complex everyday activities experienced by individuals with mTBI.

Effects of Early and Late Bilingualism on Resting-State Functional Connectivity.

Of current interest is how variations in early language experience shape patterns of functional connectivity in the human brain. In the present study, we compared simultaneous (two languages from birth) and sequential (second language learned after age 5 years) bilinguals using a seed-based resting-state MRI approach. We focused on the inferior frontal gyrus (IFG) as our ROI, as recent studies have demonstrated both neurofunctional and neurostructural changes related to age of second language acquisition in bilinguals in this cortical area. Stronger functional connectivity was observed for simultaneous bilinguals between the left and right IFG, as well as between the inferior frontal gyrus and brain areas involved in language control, including the dorsolateral prefrontal cortex, inferior parietal lobule, and cerebellum. Functional connectivity between the left IFG and the right IFG and right inferior parietal lobule was also significantly correlated with age of acquisition for sequential bilinguals; the earlier the second language was acquired, the stronger was the functional connectivity. In addition, greater functional connectivity between homologous regions of the inferior frontal gyrus was associated with reduced neural activation in the left IFG during speech production. The increased connectivity at rest and reduced neural activation during task performance suggests enhanced neural efficiency in this important brain area involved in both speech production and domain-general cognitive processing. Together, our findings highlight how the brain's intrinsic functional patterns are influenced by the developmental timeline in which second language acquisition occurs. SIGNIFICANCE STATEMENT: Of current interest is how early life experience leaves its footprint on brain structure and function. In this regard, bilingualism provides an optimal way to determine the effects of the timing of language learning because a second language can be learned from birth or later in life. We used resting-state fMRI to look at simultaneous and sequential bilinguals who differed only in age of acquisition, and found stronger connectivity between language and cognitive control regions in bilinguals who learned their two languages simultaneously, a pattern that was associated with more efficient brain activation during speech. Our findings highlight how functional connections in the brain differ depending upon when learning takes place.

Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network.

The timing of language learning shapes brain structure associated with articulation.

We compared the brain structure of highly proficient simultaneous (two languages from birth) and sequential (second language after age 5) bilinguals, who differed only in their degree of native-like accent, to determine how the brain develops when a skill is acquired from birth versus later in life. For the simultaneous bilinguals, gray matter density was increased in the left putamen, as well as in the left posterior insula, right dorsolateral prefrontal cortex, and left and right occipital cortex. For the sequential bilinguals, gray matter density was increased in the bilateral premotor cortex. Sequential bilinguals with better accents also showed greater gray matter density in the left putamen, and in several additional brain regions important for sensorimotor integration and speech-motor control. Our findings suggest that second language learning results in enhanced brain structure of specific brain areas, which depends on whether two languages are learned simultaneously or sequentially, and on the extent to which native-like proficiency is acquired.

Past experience shapes ongoing neural patterns for language.

Early experiences may establish a foundation for later learning, however, influences of early language experience on later neural processing are unknown. We investigated whether maintenance of neural templates from early language experience influences subsequent language processing. Using fMRI, we scanned the following three groups performing a French phonological working memory (PWM) task: (1) monolingual French children; (2) children adopted from China before age 3 who discontinued Chinese and spoke only French; (3) Chinese-speaking children who learned French as a second language but maintained Chinese. Although all groups perform this task equally well, brain activation differs. French monolinguals activate typical PWM brain regions, while both Chinese-exposed groups also activate regions implicated in cognitive control, even the adoptees who were monolingual French speakers at testing. Early exposure to a language, and/or delayed exposure to a subsequent language, continues to influence the neural processing of subsequently learned language sounds years later even in highly proficient, early-exposed users.