Tumor location and reduction in functional MRI estimates of language laterality.

OBJECTIVE: Brain tumors located close to the language cortex may distort functional MRI (fMRI)-based estimates of language dominance. The nature of this distortion, and whether this is an artifact of numerous confounders, remains unknown. The authors hypothesized tumor bias based on laterality estimates independent of confounders and that the effects are the greatest for tumors proximal to Broca's area. METHODS: To answer this question, the authors reviewed more than 1113 patients who underwent preoperative fMRI to match samples on 11 known confounders (tumor location, size, type, and grade; seizure history; prior neurosurgery; aphasia presence and severity; and patient age, sex, and handedness). The samples included 30 patients with left hemisphere tumors (15 anterior and 15 posterior) and 30 with right hemisphere tumors (15 anterior and 15 posterior), thus totaling 60 patients (25 women; 18 left-handed and 4 ambidextrous; mean age 47 [SD 14.1] years). Importantly, the authors matched not only patients with left and right hemisphere tumors but also those with anterior and posterior tumors. Standard fMRI laterality indices (LIs) were calculated using whole-brain and region of interest (ROI) approaches (Broca's and Wernicke's areas). RESULTS: Tumors close to Broca's area in the left hemisphere decreased LIs independently of known confounders. At the whole-brain level, this appeared to reflect a decrease in LI values in patients with left anterior tumors compared with patients with right anterior tumors. ROI analysis replicated these findings. Broca's area LIs were significantly lower (p = 0.02) in patients with left anterior tumors (mean LI 0.28) when compared with patients with right anterior tumors (mean LI 0.70). Changes in Wernicke's area-based LIs did not differ as a function of the tumor hemisphere. Therefore, in patients with left anterior tumors, it is essential to assess language laterality using left posterior ROIs. In all remaining tumor groups (left posterior tumors and right hemisphere tumors), language laterality derived from the anterior language ROI was the most robust measure of language dominance. CONCLUSIONS: Patients with tumors close to Broca's area showed more bilateral fMRI language maps independent of known confounders. The authors caution against the assumption that this reduced language laterality suggests no or little risk to language function following tumor resection in the left inferior frontal gyrus. Their results address how to interpret fMRI data for neurosurgical purposes, along with theoretical questions of contralesional functional compensation and disinhibition.

The Lifespan Human Connectome Project in Aging: An overview.

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018).

Functional magnetic resonance imaging of divergent and convergent thinking in Big-C creativity.

The cognitive and physiological processes underlying creativity remain unclear, and very few studies to date have attempted to identify the behavioral and brain characteristics that distinguish exceptional ("Big-C") from everyday ("little-c") creativity. The Big-C Project examined functional brain responses during tasks demanding divergent and convergent thinking in 35 Big-C Visual Artists (VIS), 41 Big-C Scientists (SCI), and 31 individuals in a "smart comparison group" (SCG) matched to the Big-C groups on parental educational attainment and estimated IQ. Functional MRI (fMRI) scans included two activation paradigms widely used in prior creativity research, the Alternate Uses Task (AUT) and Remote Associates Task (RAT), to assess brain function during divergent and convergent thinking, respectively. Task performance did not differ between groups. Functional MRI activation in Big-C and SCG groups differed during the divergent thinking task. No differences in activation were seen during the convergent thinking task. Big-C groups had less activation than SCG in frontal pole, right frontal operculum, left middle frontal gyrus, and bilaterally in occipital cortex. SCI displayed lower frontal and parietal activation relative to the SCG when generating alternate uses in the AUT, while VIS displayed lower frontal activation than SCI and SCG when generating typical qualities (the control condition in the AUT). VIS showed more activation in right inferior frontal gyrus and left supramarginal gyrus relative to SCI. All groups displayed considerable overlapping activation during the RAT. The results confirm substantial overlap in functional activation across groups, but suggest that exceptionally creative individuals may depend less on task-positive networks during tasks that demand divergent thinking.

Improving language mapping in clinical fMRI through assessment of grammar.

INTRODUCTION: Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain. METHOD: We compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates. RESULTS: The grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing. CONCLUSION: The grammar tests may be an important addition to the standard pre-operative fMRI testing.

Lateralizing language function with pre-operative functional magnetic resonance imaging in early proficient bilingual patients.

Research on bilinguals with brain lesions is complicated by high patient variability, making it difficult to find well-matched controls. We benefitted from a database of over 700 patients and conducted an analysis of pre-operative functional magnetic resonance imaging data to assess language dominance in 25 early, highly proficient Spanish-English bilinguals, and 25 carefully matched monolingual controls. Our results showed that early bilingualism is associated with greater bilateral hemispheric involvement, and monolingualism is associated with stronger left hemisphere lateralization (p=0.009). The bilinguals showed more pronounced right hemisphere activation (p=0.008). Although language dominance values were concordant in the bilingual group, there were a few (12%) atypical cases with different lateralization patterns in L1 and L2. Finally, we found distinct areas of activity in first and second language within the language network, in addition to regions of convergence. These data underscore the need to map all languages proficiently spoken by surgical candidates.

Language system organization in a quadrilingual with a brain tumor: Implications for understanding of the language network.

In pre-neurosurgery language mapping it is critical to identify language-specific regions in multilingual speakers. We conducted pre-operative functional magnetic resonance imaging, and intraoperative language mapping in the unique case of a highly proficient quadrilingual with a left frontal brain tumor who acquired her second language at age 5, and her third and fourth languages at 15. We found a predominantly different organization in each language with only a few areas shared by all 4 languages. Contrary to existing evidence, impairment across languages was not related to age of acquisition, amount of exposure, or language similarity. This case suggests that the functional structure of the language system may be highly idiosyncratic in multilingual individuals and supports detailed study in this group to inform neurocognitive models of language.