Carolina Mendez-Orellana

Language lateralization (LL) is a key aspect for preoperative surgical planning in patients with brain tumors. Crossed cerebro-cerebellar (CCC) activation, derived from functional magnetic resonance imaging (fMRI), guides LL determination. Structural features, such as gray matter volume (GMV), may provide complementary information on structural asymmetries associated with LL. However, the literature suggests that LL may change after surgery, and less is known about its variation over repeated surgeries. This case study aims to characterize LL in a patient with a recurrent glioma using both functional and structural measures. The case is a 33-year-old woman who underwent three intraoperative awake speech mapping tumor resections. Conventional MRI and fMRI were acquired before each surgery: 2017 (T1), 2020 (T2), and 2023 (T3). CCC activation was used as a functional marker of LL, and GMV was used to examine structural asymmetries. Linguistic and cognitive functions were examined pre-and postoperatively. Although supratentorial activation patterns showed some variability, CCC activation consistently indicated left-hemisphere LL. Structural analyses revealed differential volumetric patterns between the ipsilateral and contralateral language regions. Combining functional and structural measures, such as CCC activation and GMV analysis, may provide complementary information for assessing LL in patients undergoing repeated surgeries.

Background: Functional MRI (fMRI) studies conducted on young adults reveal a predominantly left-lateralized cortical language network during semantic and phonological processing (SP and PP, respectively). Both linguistic dimensions have been advanced as potential cognitive markers of pathological aging. However, the neural mechanisms underlying SP and PP among healthy older adults remain poorly understood.Aim: This study aimed to investigate the dynamics of language lateralization among native Spanish-speaking older adults in relation to their behavioral performance in specific semantic and phonological tasks.Methodology: Twenty-eight healthy, right-handed older Chilean adults (mean age: 67.7, SD±: 7.44, range: 60–87) took part in an fMRI session during which they performed semantic and phonological tasks. They were also evaluated for overall language performance using the Spanish version of ScreeLing and verbal fluency tasks. A fixed-effect analysis was performed to explore group-level differences. Standard regression analyses were also used to assess the association between brain activation and language performance.Results: Both SP and PP elicited bilateral activation in the pars triangularis and opercularis of the inferior frontal gyrus (IFG) and the superior temporal gyrus. Activation was also observed in the left inferior parietal gyrus. Semantic fluency performance was significantly associated with activation in the right angular gyrus and the pars opercularis of the IFG. In contrast, phonological fluency was associated with bilateral activation in the IFG pars orbitalis.Conclusion: Among healthy older adults, SP and PP recruit bilateral language-related brain regions, potentially reflecting compensatory mechanisms associated with normal aging. Notably, the IFG pars orbitalis may play a distinct role in supporting phonological fluency, despite not being a region traditionally linked to PP. Further research is needed to clarify the contribution of this region to phonological performance among aging adults.

Introduction: Structural brain changes during aging have been used as specific markers to distinguish normal aging from dementia. Changes in specific cognitive abilities such as episodic memory, processing speed, and executive functions, are observed in healthy aging. Limited evidence reports changes in linguistic functions alongside structural and functional brain changes. This study investigates correlations between language performance, gray matter volume (GMV), and neural activity in language regions, adjusted for demographic factors, in healthy older adults.Methods: Twenty-seven right-handed participants aged 60–87 were evaluated for overall linguistic performance using the Spanish version of ScreeLing (SCL) test and phonemic fluency and semantic verbal fluency tasks (PF and SF). Participants also underwent an MRI session during which they performed a functional MRI language task. T1-weighted MRI scans were used to measure GMV in specific language-related regions and assess language lateralization. Correlational analyses were conducted between language scores, GMV, years of education, age, sex, and fMRI lateralization.Results: In the right hemisphere (RH), significant positive correlations were found between SCL scores and GMV in the orbital inferior frontal gyrus (r = 0.5402; p = 0.0044) and the superior temporal gyrus (r = 0.516; p = 0.007). Furthermore, SCL and Phonemic fluency positively correlated with years of education, indicating that higher education enhances speech performance. No significant correlations were found in the left hemisphere (LH). Age, sex, and fMRI lateralization did not significantly correlate with specific linguistic scores.Discussion: These results challenge the current view of the role of the right hemisphere in language performance as increased GMV in specific right hemisphere language regions is associated with better language performance, highlighting the role of the right hemisphere in supporting language skills during healthy aging.

Background: The abbreviated version of the Token Test (aTT) is widely used to assess language comprehension deficits in stroke patients (SPs). However, aTT has not been validated for Latin American Spanish speakers, so clinicians tend to use cut‐off scores for aTT validated in developed countries.Aims: To provide normative data for the Spanish aTT (Sp‐aTT) in healthy Chilean Spanish‐speaking and SP, determining the influence of sociodemographic variables such as gender, age and education on Sp‐aTT performance.Methods & Procedures: A total of 210 healthy volunteers (age range = 18–88 years) and 197 SPs (age range = 23–94 years), all native speakers of Chilean Spanish, were recruited. The association of age, gender and years of education on the Sp‐aTT performance was analysed. Specificity and sensibility analyses of the Sp‐aTT to diagnose language comprehension deficits were completed.Outcomes & Results: Only age (p < 0.001) and years of education (p < 0.001) impacted the total score of Sp‐aTT. Gender did not show an association with Sp‐aTT performance (p = 0.181). For SPs, the Sp‐aTT score showed a significant positive correlation (rho = 0.4, p < 0.001) with the aphasia severity rating scale (ASRS) score. For Sp‐aTT, the area under the curve was 0.97, and the optimal cut‐off score for the Sp‐aTT was 30 (0.73 of sensitivity, 0.92 of specificity and a Youden index of 0.644).Conclusions & Implications: Age and years of education are two key factors to be controlled for when determining the optimal cut‐off points for the Sp‐aTT. Our results also highlight the need for language‐specific norms in stroke and aphasia research.WHAT THIS PAPER ADDS: What is already known on the subject: The aTT has been validated and adapted in several countries. Its properties in screening and detecting comprehensive deficits in SPs highlight its potential as a screening tool in clinical practice. Moreover, considering that stroke is the third largest cause of death worldwide, research and clinical practice have focused on how to improve early detection of deficits in these people, especially those related to cognition, language and functionality in SPs. Therefore, counting with validated and adapted tools is essential for clinicians because it could contribute to accurate intervention and classification of language disorders. What this paper adds to the existing knowledge: The main contribution of this study is to provide normative data for the aTT in Latin American Spanish speakers. No previous studies have focused on validating this test and analysing the influence of three critical variables (age, gender and years of education) on its performance in SPs from Latin America. In addition, we propose a classification of the severity of comprehension deficits in SPs. Finally, we found comprehension deficits in patients with right and left hemisphere stroke, which would imply that these deficits would not be exclusive to left hemisphere stroke. What are the potential or actual clinical implications of this work?: Contribute with validation of language comprehension tools, such as the aTT, could improve early diagnosis of patients with language disorders. This validation provides a test based on the sociodemographic characteristics of Latin American Speakers, which has yet to be established. Due to this, normative data considering the sociodemographic characteristics of the target population is crucial for accurately classifying comprehension deficits after brain damage.

Background/Objectives: Functional MRI (fMRI) is widely used to assess language lateralization, but its application in patients with brain tumors can be hindered by cognitive impairments, compensatory neuroplasticity, and artifacts due to patient movement or severe aphasia. Gray matter volume (GMV) analysis via voxel-based morphometry (VBM) in language-related brain regions may offer a stable complementary approach. This study investigates the relationship between GMV and fMRI-derived language lateralization in healthy individuals and patients with left-hemisphere brain tumors, aiming to enhance accuracy in complex cases. Methods: The MRI data from 22 healthy participants and 28 individuals with left-hemisphere brain tumors were analyzed. Structural T1-weighted and functional images were obtained during three language tasks. Language lateralization was assessed based on activation in predefined regions of interest (ROIs), categorized as typical (left) or atypical (right or bilateral). The GMV in these ROIs was measured using VBM. Linear regressions explored GMV-lateralization associations, and logistic regressions predicted the lateralization based on the GMV. Results: In the healthy participants, typical left-hemispheric language dominance correlated with higher GMV in the left pars opercularis of the inferior frontal gyrus. The brain tumor participants with atypical lateralization showed increased GMV in six right-hemisphere ROIs. The GMV in the language ROIs predicted the fMRI language lateralization, with AUCs from 80.1% to 94.2% in the healthy participants and 78.3% to 92.6% in the tumor patients. Conclusions: GMV analysis in language-related ROIs effectively complements fMRI for assessing language dominance, particularly when fMRI is challenging. It correlates with language lateralization in both healthy individuals and brain tumor patients, highlighting its potential in preoperative language mapping. Further research with larger samples is needed to refine its clinical utility.

Background: Semantic and Phonological fluency (SF and PF) are routinely evaluated in patients with Alzheimer’s disease (AD). There are disagreements in the literature regarding which fluency task is more affected while developing AD. Most studies focus on SF assessment, given its connection with the temporoparietal amnesic system. PF is less reported, it is related to working memory, which is also impaired in probable and diagnosed AD. Differentiating between performance on these tasks might be informative in early AD diagnosis, providing an accurate linguistic profile. Objective: Compare SF and PF performance in healthy volunteers, volunteers with probable AD, and patients with AD diagnosis, considering the heterogeneity of age, gender, and educational level variables. Methods: A total of 8 studies were included for meta-analysis, reaching a sample size of 1,270 individuals (568 patients diagnosed with AD, 340 with probable AD diagnosis, and 362 healthy volunteers). Results: The three groups consistently performed better on SF than PF. When progressing to a diagnosis of AD, we observed a significant difference in SF and PF performance across our 3 groups of interest ( p = 0.04). The age variable explained a proportion of this difference in task performance across the groups, and as age increases, both tasks equally worsen. Conclusion: The performance of SF and PF might play a differential role in early AD diagnosis. These tasks rely on partially different neural bases of language processing. They are thus worth exploring independently in diagnosing normal aging and its transition to pathological stages, including probable and diagnosed AD.

Objectives Crossed cerebro-cerebellar BOLD activations have recently come to light as additional diagnostic features for patients with brain tumors. The covert verb generation (VG) task is a widely used language paradigm to determine these language-related crossed activations. Here we demonstrate these crossed activations in two additional language paradigms, the semantic and phonological association tasks. We propose the merit of these tasks to language lateralization determination in the clinic as they are easy to monitor and suitable for patients with aphasia. Methods Patients with brain tumors localized at different cortical sites (n = 71) performed three language paradigms, namely the VG task as well as the semantic (SA) and phonological (PA) association tasks with button-press responses. Respective language activations in disparate cortical regions and the cerebellum were assigned laterality. Agreements in laterality between the two new tasks and the verb generation task were tested using Cohen’s kappa. Results Both tasks significantly agreed in cortical and cerebellar lateralization with the verb generation task in patients. Additionally, a McNemar test confirmed the presence of crossed activations in the cortex and the cerebellum in the entire subject population. Conclusion We demonstrated that the semantic and phonological association tasks resulted in crossed cerebro-cerebellar language lateralization activations as those observed due to the covert verb generation task. This may suggest the possibility of these tasks being used conjointly with the traditional verb generation task, especially for subjects that may be unable to perform the latter. Key Points • The semantic and phonological association tasks can be useful as additional presurgical fMRI language lateralization paradigms for brain tumor patients along with the standard verb generation task. • All three tasks also confirm the presence of crossed cerebro-cerebellar language activations in the current subject population.