Presurgical language fMRI: Technical practices in epilepsy surgical planning.

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.

Presurgical language fMRI: Clinical practices and patient outcomes in epilepsy surgical planning.

The goal of this study was to document current clinical practice and report patient outcomes in presurgical language functional MRI (fMRI) for epilepsy surgery. Epilepsy surgical programs worldwide were surveyed as to the utility, implementation, and efficacy of language fMRI in the clinic; 82 programs responded. Respondents were predominantly US (61%) academic programs (85%), and evaluated adults (44%), adults and children (40%), or children only (16%). Nearly all (96%) reported using language fMRI. Surprisingly, fMRI is used to guide surgical margins (44% of programs) as well as lateralize language (100%). Sites using fMRI for localization most often use a distance margin around activation of 10mm. While considered useful, 56% of programs reported at least one instance of disagreement with other measures. Direct brain stimulation typically confirmed fMRI findings (74%) when guiding margins, but instances of unpredicted decline were reported by 17% of programs and 54% reported unexpected preservation of function. Programs reporting unexpected decline did not clearly differ from those which did not. Clinicians using fMRI to guide surgical margins do not typically map known language-critical areas beyond Broca's and Wernicke's. This initial data shows many clinical teams are confident using fMRI not only for language lateralization but also to guide surgical margins. Reported cases of unexpected language preservation when fMRI activation is resected, and cases of language decline when it is not, emphasize a critical need for further validation. Comprehensive studies comparing commonly-used fMRI paradigms to predict stimulation mapping and post-surgical language decline remain of high importance.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases.

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.

Optimization of tractography of the optic radiations.

Imaging and delineation of the optic radiations (OpRs) remains challenging, despite repeated attempts to achieve reliable validated tractography of this complex structure. Previous studies have used varying methods to generate representations of the OpR which differ markedly from one another and, frequently, from the OpR's known structure. We systematically examined the influence of a key variable that has differed across previous studies, the tractography seed region, in 13 adult participants (nine male; mean age 31 years; SD 8.7 years; range 16-47). First, we compared six seed regions at the lateral geniculate nucleus (LGN) and sagittal stratum based on the literature and known OpR anatomy. Three of the LGN regions seeded streamlines consistent with the OpR's three "bundles," whereas a fourth seeded streamlines consistent with each of the three bundles. The remaining two generated OpR streamlines unreliably and inconsistently. Two stratum regions seeded the radiations. This analysis identified a set of optimal regions of interest (ROI) for seeding OpR tractography and important inclusion and exclusion ROI. An optimized approach was then used to seed LGN regions to the stratum. The radiations, including streamlines consistent with Meyer's Loop, were streamlined in all cases. Streamlines extended 0.2 ± 2.4 mm anterior to the tip of the anterior horn of the lateral ventricle. These data suggest some existing approaches likely seed representations of the OpR that are visually plausible but do not capture all OpR components, and that using an optimized combination of regions seeded previously allows optimal mapping of this complex structure.

What's the story? The tale of reading fluency told at speed.

Fluent readers process written text rapidly and accurately, and comprehend what they read. Historically, reading fluency has been modeled as the product of discrete skills such as single word decoding. More recent conceptualizations emphasize that fluent reading is the product of competency in, and the coordination of, multiple cognitive sub-skills (a multi-componential view). In this study, we examined how the pattern of activation in core reading regions changes as the ability to read fluently is manipulated through reading speed. We evaluated 13 right-handed adults with a novel fMRI task assessing fluent sentence reading and lower-order letter reading at each participant's normal fluent reading speed, as well as constrained (slowed) and accelerated reading speeds. Comparing fluent reading conditions with rest revealed regions including bilateral occipito-fusiform, left middle temporal, and inferior frontal gyral clusters across reading speeds. The selectivity of these regions' responses to fluent sentence reading was shown by comparison with the letter reading task. Region of interest analyses showed that at constrained and accelerated speeds these regions responded significantly more to fluent sentence reading. Critically, as reading speed increased, activation increased in a single reading-related region: occipital/fusiform cortex (left > right). These results demonstrate that while brain regions engaged in reading respond selectively during fluent reading, these regions respond differently as the ability to read fluently is manipulated. Implications for our understanding of reading fluency, reading development, and reading disorders are discussed.

Cognitive Biomarkers in the Clinic: Lessons From Presurgical fMRI.

SUMMARY: Cognitive biomarkers are vital and uniquely challenging clinical tools. There has been marked growth in neuroimaging-based cognitive biomarkers across the past 40 years with more in development (e.g., clinical cognitive EEG). The challenges involved in developing cognitive biomarkers and key milestones in their development are reviewed here using clinical functional MRI's evolution as a case study. It is argued that indexing cognition is uniquely challenging because it requires patients to consistently use specific cognitive processes, and it is difficult or impossible to independently verify this occurred. This limitation can be successfully managed through careful analysis of standardized protocols for acquisition and interpretation, and ensuring the clinical application of biomarkers integrates disciplines with complementary expertise. Factors beneficial to the adoption of a novel cognitive biomarker include a clinical need and inadequate alternatives. Key milestones in the development of functional MRI included (1) demonstration that its performance was equivalent to its predecessor; (2) demonstration it predicted a clinically meaningful outcome; and (3) the establishment of infrastructure for both its execution and billing. Review of functional MRI and its predecessors suggest a cycle whereby successful cognitive biomarkers are validated, experience widespread adoption and customization/fragmentation, go through a period of review, and finally are refined and standardized. Those applying future cognitive biomarkers in the clinic can avoid some of the failures of clinical functional MRI by defining the skills and disciplines the method requires and routinely evaluating patient outcomes.

Electrical cortical stimulation can impair production of the alphabet without impairing counting.

Neurosurgery has the potential to cure patients with drug-resistant focal epilepsy, but carries the risk of permanent language impairment when surgery involves the dominant hemisphere of the brain. This risk can be estimated and minimized using electrical stimulation mapping (ESM), which uses cognitive and linguistic tasks during cortical ESM to differentiate "eloquent" and "resectable" areas in the brain. One such task, counting, is often used to screen and characterize language during ESM in patients whose language abilities are limited. Here we report a patient with drug-resistant epilepsy arising from the language-dominant hemisphere using fMRI. Our patient experienced loss of the ability to recite or write the alphabet, but not to count, during ESM of the dominant left posterior superior temporal gyrus. This selective impairment extended to both spoken and written production. We suggest the need for caution when using counting as a sole means to screen language function and as a method of testing low functioning patients using ESM.

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.

Elemental spatial and temporal association formation in left temporal lobe epilepsy.

The mesial temporal lobe (MTL) is typically understood as a memory structure in clinical settings, with the sine qua non of MTL damage in epilepsy being memory impairment. Recent models, however, understand memory as one of a number of higher cognitive functions that recruit the MTL through their reliance on more fundamental processes, such as "self-projection" or "association formation". We examined how damage to the left MTL influences these fundamental processes through the encoding of elemental spatial and temporal associations. We used a novel fMRI task to image the encoding of simple visual stimuli, either rich or impoverished, in spatial or spatial plus temporal information. Participants included 14 typical adults (36.4 years, sd. 10.5 years) and 14 patients with left mesial temporal lobe damage as evidenced by a clinical diagnosis of left temporal lobe epilepsy (TLE) and left MTL impairment on imaging (34.3 years, sd. 6.6 years). In-scanner behavioral performance was equivalent across groups. In the typical group whole-brain analysis revealed highly significant bilateral parahippocampal activation (right > left) during spatial associative processing and left hippocampal/parahippocampal deactivation in joint spatial-temporal associative processing. In the left TLE group identical analyses indicated patients used MTL structures contralateral to the seizure focus differently and relied on extra-MTL regions to a greater extent. These results are consistent with the notion that epileptogenic MTL damage is followed by reorganization of networks underlying elemental associative processes. In addition, they provide further evidence that task-related fMRI deactivation can meaningfully index brain function. The implications of these findings for clinical and cognitive neuropsychological models of MTL function in TLE are discussed.