Deep reasoning neural network analysis to predict language deficits from psychometry-driven DWI connectome of young children with persistent language concerns.

This study investigated whether current state-of-the-art deep reasoning network analysis on psychometry-driven diffusion tractography connectome can accurately predict expressive and receptive language scores in a cohort of young children with persistent language concerns (n = 31, age: 4.25 ± 2.38 years). A dilated convolutional neural network combined with a relational network (dilated CNN + RN) was trained to reason the nonlinear relationship between "dilated CNN features of language network" and "clinically acquired language score". Three-fold cross-validation was then used to compare the Pearson correlation and mean absolute error (MAE) between dilated CNN + RN-predicted and actual language scores. The dilated CNN + RN outperformed other methods providing the most significant correlation between predicted and actual scores (i.e., Pearson's R/p-value: 1.00/<.001 and .99/<.001 for expressive and receptive language scores, respectively) and yielding MAE: 0.28 and 0.28 for the same scores. The strength of the relationship suggests elevated probability in the prediction of both expressive and receptive language scores (i.e., 1.00 and 1.00, respectively). Specifically, sparse connectivity not only within the right precentral gyrus but also involving the right caudate had the strongest relationship between deficit in both the expressive and receptive language domains. Subsequent subgroup analyses inferred that the effectiveness of the dilated CNN + RN-based prediction of language score(s) was independent of time interval (between MRI and language assessment) and age of MRI, suggesting that the dilated CNN + RN using psychometry-driven diffusion tractography connectome may be useful for prediction of the presence of language disorder, and possibly provide a better understanding of the neurological mechanisms of language deficits in young children.

Novel FOXP1 pathogenic variants in two Indian subjects with syndromic intellectual disability.

We describe two unrelated Indian boys with Mental retardation with language impairment with or without autistic features (OMIM#613670). Novel pathogenic variants c. 593_599 delins AGAAG and c.1556T>C in FOXP1 were identified in Patients 1 and 2, respectively by exome sequencing. The patients shared the cardinal features of significant language impairment, prominent forehead, downslanted palpebral fissures, frontal upsweep of hair, and behavioral abnormalities. Camptodactyly (with pterygia in Patient 2) was an additional feature noted in our study. The phenotype was consistent with previous reports of patients with monogenic defects in FOXP1. The facial features overlap with Sotos syndrome. However, presence of frontal upsweep of hair is a good pointer toward FOXP1 related syndromic intellectual disability.

Asymmetric Bálint's syndrome with multimodal agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading due to subcortical hemorrhage in the left parieto-occipito-temporal area.

We report a patient with asymmetric Bálint's syndrome (predominantly right-sided oculomotor apraxia and simultanagnosia and optic ataxia for the right hemispace), and multimodal agnosia (apperceptive visual agnosia and bilateral associative tactile agnosia) with accompanying right hemianopia, bilateral agraphesthesia, hemispatial neglect, global alexia with unavailable kinesthetic reading, and lexical agraphia for kanji (Japanese morphograms), after hemorrhage in the left parieto-occipito-temporal area. The coexistence of tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading suggests that tactile-kinesthetic information can be interrupted because of damage to the fiber connection from the parietal lobe to the occipito-temporal area, leading to these tactually related cognitive impairments.

Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review.

The CAMK2B gene encodes the ß-subunit of calcium/calmodulin-dependent protein kinase II (CAMK2), an enzyme that has crucial roles in synaptic plasticity, especially in hippocampal and cerebellar neurons. Heterozygous variants in CAMK2B cause a rare neurodevelopmental disorder, with 40% of the reported cases sharing the same variant: c.416C>T, p.(P139L). This case report describes a 22-year-old patient with this recurrent variant, who presents with severe intellectual disability, absence of language, hypotonia, microcephaly, dysmorphic features, epilepsy, behavioral abnormalities, motor stereotypies, optic atrophy, and progressive cerebellar atrophy. Notably, this patient is the oldest reported so far and allows us to better delineate the clinical phenotype associated with this variant, adding clinical aspects never described before, such as epilepsy, optic atrophy, scoliosis, and neuroradiological changes characterized by progressive cerebellar atrophy.

7q31.2q31.31 deletion downstream of FOXP2 segregating in a family with speech and language disorder.

Chromosomal 7q31 deletions have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. These copy number variants usually encompass FOXP2, haploinsufficiency of which represents a widely acknowledged cause for specific speech and language disorders. By chromosomal microarray analysis we identified a 4.7 Mb microdeletion at 7q31.2q31.31 downstream of FOXP2 in three family members presenting with variable speech, language and neurodevelopmental phenotypes. The index individual showed delayed speech development with impaired speech production, reduced language comprehension, and additionally learning difficulties, microcephaly, and attention deficit. His younger sister had delayed speech development with impaired speech production and partially reduced language comprehension. Their mother had attended a school for children with speech and language deficiencies and presented with impaired articulation. The deletion had occurred de novo in the mother, includes 15 protein-coding genes and is located in close proximity to the 3' end of FOXP2. Though a novel locus at 7q31.2q31.31 associated with mild neurodevelopmental and more prominent speech and language impairment is possible, the close phenotypic overlap with FOXP2-associated speech and language disorder rather suggests a positional effect on FOXP2 expression and function.

Lexical-semantic search related to side of onset and putamen volume in Parkinson's disease.

Parkinson's disease (PD) is characterized by dopaminergic cell loss and reduced striatal volume. Prior studies have demonstrated striatal involvement in access to lexical-semantic knowledge and damage to this structure may be evident in the lexical properties of responses. Semantic fluency task responses from early stage, non-demented PD participants with right (PD-R) or left (PD-L) lateralizing symptoms were compared to matched controls on lexical properties (word frequency, age of acquisition) and correlated with striatal volumes segmented from T1-weighted brain MR images. PD-R participants produced semantic fluency responses of a lower age of acquisition than PD-L and control participants (p < 0.05). PD-R age of acquisition responses correlated positively with putamen volume (p < 0.05), while age of acquisition of responses correlated negatively with caudate volume in controls (p < 0.05). Findings provide evidence for a role of the striatum in lexical-semantic access and qualitative changes in lexical access in select PD patients.

Pure word deafness in a patient with bilateral ischemic stroke in the superior temporal gyrus (STG).

INTRODUCTION: Pure word deafness is a rare neurological disorder linked with an inability to comprehend speech. The precise localization of damage is still unclear. CASE PRESENTATION: A 72-year-old woman presented with acute verbal contact disturbances, disorientation, and anxiety. In the neurological examination a slight right hemiparesis was found, together with a pure word deafness (PWD) in neuropsychological tests. Neuroimages confirmed bilateral ischemic lesions in the superior temporal gyrus (STG) acute in the left hemisphere. CONCLUSIONS: Our case suggested that bilateral, symmetric lesions in the region of STG could cause pure world deafness. The diversity and severity of symptoms confirm the necessity of pure world deafness classification for subtypes.

Structural analysis of pathogenic missense mutations in GABRA2 and identification of a novel de novo variant in the desensitization gate.

BACKGROUND: Cys-loop receptors control neuronal excitability in the brain and their dysfunction results in numerous neurological disorders. Recently, six missense variants in GABRA2, a member of this family, have been associated with early infantile epileptic encephalopathy (EIEE). We identified a novel de novo missense variant in GABRA2 in a patient with EIEE and performed protein structural analysis of the seven variants. METHODS: The novel variant was identified by trio whole-genome sequencing. We performed protein structural analysis of the seven variants, and compared them to previously reported pathogenic mutations at equivalent positions in other Cys-loop receptors. Additionally, we studied the distribution of disease-associated variants in the transmembrane helices of these proteins. RESULTS: The seven variants are in the transmembrane domain, either close to the desensitization gate, the activation gate, or in inter-subunit interfaces. Six of them have pathogenic mutations at equivalent positions in other Cys-loop receptors, emphasizing the importance of these residues. Also, pathogenic mutations are more common in the pore-lining helix, consistent with this region being highly constrained for variation in control populations. CONCLUSION: Our study reports a novel pathogenic variant in GABRA2, characterizes the regions where pathogenic mutations are in the transmembrane helices, and underscores the value of considering sequence, evolutionary, and structural information as a strategy for variant interpretation of novel missense mutations.

Language and spatial dysfunction in Alzheimer disease with white matter thorn-shaped astrocytes.

OBJECTIVES: Alzheimer disease (AD) shows a broad array of clinical presentations, but the mechanisms underlying these phenotypic variants remain elusive. Aging-related astrogliopathy (ARTAG) is a relatively recent term encompassing a broad array of tau deposition in astroglia outside the range of traditional tauopathies. White matter thorn-shaped astrocyte (WM-TSA) clusters, a specific ARTAG subtype, has been associated with atypical language presentation of AD in a small study lacking replication. To interrogate the impact of WM-TSA in modifying clinical phenotype in AD, we investigated a clinicopathologic sample of 83 persons with pure cortical AD pathology and heterogeneous clinical presentations. METHODS: We mapped WM-TSA presence and density throughout cortical areas and interrogated whether WM-TSA correlated with atypical AD presentation or worse performance in neuropsychological testing. RESULTS: WM-TSA was present in nearly half of the cases and equally distributed in typical and atypical AD presentations. Worsening language and visuospatial functions were correlated with higher WM-TSA density in language-related and visuospatial-related regions, respectively. These findings were unrelated to regional neurofibrillary tangle burden. Next, unsupervised clustering divided the participants into 2 groups: a high-WM-TSA (n = 9) and low-WM-TSA (n = 74) pathology signature. The high-WM-TSA group scored significantly worse in language but not in other cognitive domains. CONCLUSIONS: The negative impact of WM-TSA pathology to language and possibly visuospatial networks suggests that WM-TSA is not as benign as other ARTAG types and may be explored as a framework to understand the mechanisms and impact of astrocytic tau deposition in AD in humans.

The white matter connectome as an individualized biomarker of language impairment in temporal lobe epilepsy.

OBJECTIVE: The distributed white matter network underlying language leads to difficulties in extracting clinically meaningful summaries of neural alterations leading to language impairment. Here we determine the predictive ability of the structural connectome (SC), compared with global measures of white matter tract microstructure and clinical data, to discriminate language impaired patients with temporal lobe epilepsy (TLE) from TLE patients without language impairment. METHODS: T1- and diffusion-MRI, clinical variables (CVs), and neuropsychological measures of naming and verbal fluency were available for 82 TLE patients. Prediction of language impairment was performed using a robust tree-based classifier (XGBoost) for three models: (1) a CV-model which included demographic and epilepsy-related clinical features, (2) an atlas-based tract-model, including four frontotemporal white matter association tracts implicated in language (i.e., the bilateral arcuate fasciculus, inferior frontal occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus), and (3) a SC-model based on diffusion MRI. For the association tracts, mean fractional anisotropy was calculated as a measure of white matter microstructure for each tract using a diffusion tensor atlas (i.e., AtlasTrack). The SC-model used measurement of cortical-cortical connections arising from a temporal lobe subnetwork derived using probabilistic tractography. Dimensionality reduction of the SC was performed with principal components analysis (PCA). Each model was trained on 49 patients from one epilepsy center and tested on 33 patients from a different center (i.e., an independent dataset). Randomization was performed to test the stability of the results. RESULTS: The SC-model yielded a greater area under the curve (AUC; .73) and accuracy (79%) compared to both the tract-model (AUC: .54, p < .001; accuracy: 70%, p < .001) and the CV-model (AUC: .59, p < .001; accuracy: 64%, p < .001). Within the SC-model, lateral temporal connections had the highest importance to model performance, including connections similar to language association tracts such as links between the superior temporal gyrus to pars opercularis. However, in addition to these connections many additional connections that were widely distributed, bilateral and interhemispheric in nature were identified as contributing to SC-model performance. CONCLUSION: The SC revealed a white matter network contributing to language impairment that was widely distributed, bilateral, and lateral temporal in nature. The distributed network underlying language may be why the SC-model has an advantage in identifying sub-components of the complex fiber networks most relevant for aspects of language performance.

Mapping eloquent cortex: A voxel-based lesion-symptom mapping study of core speech production capacities in brain tumour patients.

This study used voxel-based lesion-symptom mapping to examine the cortical and white matter regions associated with language production impairments in a sample of 63 preoperative tumour patients. We identified four cognitive functions considered crucial for spoken language production: semantic-to-lexical mapping (selecting the appropriate lexical label for the intended concept); phonological encoding (retrieving the word's phonological form); articulatory-motor planning (programming the articulatory motor movements); and goal-driven language selection (exerting top-down control over the words selected for production). Each participant received a score estimating their competence on each function. We then mapped the region(s) where pathology was significantly associated with low scores. For semantic-to-lexical mapping, the critical map encompassed portions of the left posterior middle and inferior temporal gyri, extending into posterior fusiform gyrus, overlapping substantially with the territory of the inferior longitudinal fasciculus. For phonological encoding, the map encompassed the left inferior parietal lobe and posterior middle temporal gyrus, overlapping with the territory of the inferior longitudinal and posterior arcuate fasciculi. For articulatory-motor planning, the map encompassed parts of the left frontal pole, frontal operculum, and inferior frontal gyrus, and overlapped with the territory of the frontal aslant tract. Finally, the map for goal-driven language selection encompassed the left frontal pole and the anterior cingulate cortex. We compare our findings with those from other neuropsychological samples, and conclude that the study of tumour patients offers evidence that complements that available from other populations.

Non-linear spelling in writing after a pure cerebellar lesion.

The most common deficits in processing written language result from damage to the graphemic buffer system and refer to semantic and lexical problems or difficulties in phoneme-graphene conversion. However, a writing disorder that has not yet been studied in depth is the non-linear spelling phenomenon. Indeed, although some cases have been described, no report has exhaustively explained the cognitive mechanism and the anatomical substrates underlying this process. In the present study, we analyzed the modality of non-linear writing in a patient affected by a focal cerebellar lesion, who presented with an alteration of the normal trend to write the order of the letters. Based on this evidence, we analyzed the functional connectivity between the cerebellum and the brain network that subtends handwriting and demonstrated how the cerebellar lesion of the patient affected the connections between the cerebellum and cortical areas that support the anatomical system of writing. This is the first report of non-linear spelling in a patient with a lesion outside the fronto-parietal network, specifically with a focal cerebellar lesion. We propose that non-linear writing can be interpreted in view of the role of the cerebellum in timing and sequential processing. Thus, considering the current functional connectivity data, we hypothesize that the cerebellum might be relevant in the mechanism that allows the correct activation timing of letters within a string and placement of the letters in a specific sequential writing order.

Functional connectivity of language networks after perinatal stroke.

Successful language acquisition during development is imperative for lifelong function. Complex language networks develop throughout childhood. Perinatal stroke may cause significant language disabilities but function can also be remarkably normal. Studying such very early brain injury populations may inform developmental plasticity models of language networks. We examined functional connectivity (FC) of language networks in children with arterial and venous perinatal stroke and typically developing controls (TDC) in a population-based, controlled, cohort study. Resting state functional MRI was performed at 3 T (TR/TE = 2000/30 ms, 150 volumes, 3.6mm3 voxels). Seed-based analyses used bilateral inferior frontal and superior temporal gyri. A subset of stroke participants completed clinical language testing. Sixty-six children participated (median age: 12.85±3.8y, range 6-19; arterial N = 17; venous N = 15; TDC N = 34]. Children with left hemisphere strokes had comparable FC in their right hemispheres compared to TDC. Inter- and intra-hemispheric connectivity strengths were similar between TDC and PVI but lower for AIS. Reduced FC was associated with poorer language comprehension. Language networks can be estimated using resting-state fMRI in children with perinatal stroke. Altered connectivity may occur in both hemispheres, is more pronounced with arterial lesions, and is associated with clinical function. Our results have implications for therapeutic language interventions after early stroke.

The Artery of Aphasia, A Uniquely Sensitive Posterior Temporal Middle Cerebral Artery Branch that Supplies Language Areas in the Brain: Anatomy and Report of Four Cases.

BACKGROUND: Arterial disruption during brain surgery can cause devastating injuries to wide expanses of white and gray matter beyond the tumor resection cavity. Such damage may occur as a result of disrupting blood flow through en passage arteries. Identification of these arteries is critical to prevent unforeseen neurologic sequelae during brain tumor resection. In this study, we discuss one such artery, termed the artery of aphasia (AoA), which when disrupted can lead to receptive and expressive language deficits. METHODS: We performed a retrospective review of all patients undergoing an awake craniotomy for resection of a glioma by the senior author from 2012 to 2018. Patients were included if they experienced language deficits secondary to postoperative infarction in the left posterior temporal lobe in the distribution of the AoA. The gross anatomy of the AoA was then compared with activation likelihood estimations of the auditory and semantic language networks using coordinate-based meta-analytic techniques. RESULTS: We identified 4 patients with left-sided posterior temporal artery infarctions in the distribution of the AoA on diffusion-weighted magnetic resonance imaging. All 4 patients developed substantial expressive and receptive language deficits after surgery. Functional language improvement occurred in only 2/4 patients. Activation likelihood estimations localized parts of the auditory and semantic language networks in the distribution of the AoA. CONCLUSIONS: The AoA is prone to blood flow disruption despite benign manipulation. Patients seem to have limited capacity for speech recovery after intraoperative ischemia in the distribution of this artery, which supplies parts of the auditory and semantic language networks.

Atypical language representation is unfavorable for language abilities following childhood stroke.

Brain plasticity has often been quoted as a reason for the more favorable outcome in childhood stroke compared to adult stroke. We investigated the relationship between language abilities and language localization in childhood stroke. Seventeen children and adolescents with left- or right-sided ischemic stroke and 18 healthy controls were tested with a comprehensive neurolinguistic test battery, and the individual neural representation of language was measured with an fMRI language paradigm. Overall, 12 of 17 stroke patients showed language abilities below average, and five patients exhibited impaired language performance. fMRI revealed increased activity in right hemisphere areas homotopic to left hemisphere language regions. In sum, seven stroke patients revealed atypical, i.e. bilateral or right lateralized language representation. Typical left hemispheric language lateralization was associated with better performance in naming and word fluency, whereas increased involvement of right homologues was accompanied by worse language outcome. In contrast, lesion lateralization or lesion volume did not correlate with language outcome or atypical language lateralization. Thus, atypical language lateralization is unfavorable for language outcome, and right homologues do not have the same cognitive capacity, even in young children.

Language Disorders in Huntington Disease: A Systematic Literature Review.

OBJECTIVE: A systematic review examining the presence and nature of language disorders associated with Huntington disease (HD). BACKGROUND: HD is characterized by gradual motor dysfunction, psychiatric problems, and cognitive decline. Communication abilities in HD may be affected not only by dysarthria but also by language impairment. However, the nature and type of this impairment is not well defined. METHODS: We searched the PubMed and PsycINFO databases and selected studies on the basis of the original language of the article, peer-review status, and specificity of the results regarding language and communication disorders. RESULTS: Thirty-one articles meeting the selection criteria were selected for this review. According to most of the studies, individuals with HD present with primary deficits of language. However, a few authors suggested that language deficits in HD result from nonlinguistic impairments, or that language abilities are largely preserved. More specifically, studies showed that HD is associated with difficulties in producing and understanding sentences and discourse, processing semantic representations of object and action concepts, retrieving lexical forms of nouns, and applying morphological and syntactic rules. There is some disagreement regarding whether HD affects reading abilities, sentence production, semantic processing, and application of morphological rules in verb conjugation. CONCLUSIONS: Although people with HD present with language impairment, further studies are needed to identify their functional origin. Clinical studies are also needed to determine the impact of such impairments on an individual's functional communication in daily living and to chart the progression of the impairments over the course of the disease.

How right hemisphere damage after stroke can impair speech comprehension.

Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.

Predicting language outcomes after stroke: Is structural disconnection a useful predictor?

For many years, researchers have sought to understand whether and when stroke survivors with acquired language impairment (aphasia) will recover. There is broad agreement that lesion location information should play some role in these predictions, but still no consensus on the best or right way to encode that information. Here, we address the emerging emphasis on the structural connectome in this work - specifically the claim that disrupted white matter connectivity conveys important, unique prognostic information for stroke survivors with aphasia. Our sample included 818 stroke patients extracted from the PLORAS database, which associates structural MRI from stroke patients with language assessment scores from the Comprehensive Aphasia Test (CAT) and basic demographic. Patients were excluded when their lesions were too diffuse or small (<1 cm3) to be detected by the Automatic Lesion Identification toolbox, which we used to encode patients' lesions as binary lesion images in standard space. Lesions were encoded using the 116 regions defined by the Automatic Anatomical Labelling atlas. We examined prognostic models driven by both "lesion load" in these regions (i.e. the proportion of each region destroyed by each patient's lesion), and by the disconnection of the white matter connections between them which was calculated via the Network Modification toolbox. Using these data, we build a series of prognostic models to predict first one ("naming"), and then all of the language scores defined by the CAT. We found no consistent evidence that connectivity disruption data in these models improved our ability to predict any language score. This may be because the connectivity disruption variables are strongly correlated with the lesion load variables: correlations which we measure both between pairs of variables in their original form, and between principal components of both datasets. Our conclusion is that, while both types of structural brain data do convey useful, prognostic information in this domain, they also appear to convey largely the same variance. We conclude that connectivity disruption variables do not help us to predict patients' language skills more accurately than lesion location (load) data alone.

Disrupted dynamic network reconfiguration of the language system in temporal lobe epilepsy.

Temporal lobe epilepsy tends to reshape the language system causing maladaptive reorganization that can be characterized by task-based functional MRI, and eventually can contribute to surgical decision making processes. However, the dynamic interacting nature of the brain as a complex system is often neglected, with many studies treating the language system as a static monolithic structure. Here, we demonstrate that as a specialized and integrated system, the language network is inherently dynamic, characterized by rich patterns of regional interactions, whose transient dynamics are disrupted in patients with temporal lobe epilepsy. Specifically, we applied tools from dynamic network neuroscience to functional MRI data collected from 50 temporal lobe epilepsy patients and 30 matched healthy controls during performance of a verbal fluency task, as well as during rest. By assigning 16 language-related regions into four subsystems (i.e. bilateral frontal and temporal), we observed regional specialization in both the probability of transient interactions and the frequency of such changes, in both healthy controls and patients during task performance but not rest. Furthermore, we found that both left and right temporal lobe epilepsy patients displayed reduced interactions within the left frontal 'core' subsystem compared to the healthy controls, while left temporal lobe epilepsy patients were unique in showing enhanced interactions between the left frontal 'core' and the right temporal subsystems. Also, both patient groups displayed reduced flexibility in the transient interactions of the left temporal and right frontal subsystems, which formed the 'periphery' of the language network. Importantly, such group differences were again evident only during task condition. Lastly, through random forest regression, we showed that dynamic reconfiguration of the language system tracks individual differences in verbal fluency with superior prediction accuracy compared to traditional activation-based static measures. Our results suggest dynamic network measures may be an effective biomarker for detecting the language dysfunction associated with neurological diseases such as temporal lobe epilepsy, specifying both the type of neuronal communications that are missing in these patients and those that are potentially added but maladaptive. Further advancements along these lines, transforming how we characterize and map language networks in the brain, have a high probability of altering clinical decision making in neurosurgical centres.10.1093/brain/awy042_video1awy042media15754656112001.