Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Right hemispheric structural connectivity and poststroke language recovery.

Poststroke aphasia typically results from brain damage to the left-lateralized language network. The contribution of the right-lateralized homologues in aphasia recovery remains equivocal. In this longitudinal observational study, we specifically investigated the role of right hemisphere structural connectome in aphasia recovery. Twenty-two patients with aphasia after a left hemispheric stroke underwent comprehensive language assessment at the early subacute and chronic stages. A novel structural connectometry approach, using multi-shell diffusion-weighted MRI data collected at the early subacute stage, was used to evaluate the relationship between right hemisphere white matter connectome and language production and comprehension abilities at early subacute stage. Moreover, we evaluated the relationship between early subacute right hemisphere white matter connectome and longitudinal change in language production and comprehension abilities. All results were corrected for multiple comparisons. Connectometry analyses revealed negative associations between early subacute stage right hemisphere structural connectivity and language production, both cross-sectionally and longitudinally (pFDR < .0125). In turn, only positive associations between right hemisphere structural connectivity and language comprehension were observed, both cross-sectionally and longitudinally (pFDR < .0125). Interhemispheric connectivity was highly associated with comprehension scores. Our results shed light on the discordant interpretations of previous findings, by providing evidence that while some right hemisphere white matter pathways may make a maladaptive contribution to the recovery of language, other pathways support the recovery of language, especially comprehension abilities.

Structural white matter connectometry of reading and dyslexia.

Current views on the neural network subserving reading and its deficits in dyslexia rely largely on evidence derived from functional neuroimaging studies. However, understanding the structural organization of reading and its aberrations in dyslexia requires a hodological approach, studies of which have not provided consistent findings. Here, we adopted a whole brain hodological approach and investigated relationships between structural white matter connectivity and reading skills and phonological processing in a cross-sectional study of 44 adults using individual local connectome matrix from diffusion MRI data. Moreover, we performed quantitative anisotropy aided differential tractography to uncover structural white matter anomalies in dyslexia (23 dyslexics and 21 matched controls) and their correlation to reading-related skills. The connectometry analyses indicated that reading skills and phonological processing were both associated with corpus callosum (tapetum), forceps major and minor, as well as cerebellum bilaterally. Furthermore, the left dorsal and right thalamic pathways were associated with phonological processing. Differential tractography analyses revealed structural white matter anomalies in dyslexics in the left ventral route and bilaterally in the dorsal route compared to the controls. Connectivity deficits were also observed in the corpus callosum, forceps major, vertical occipital fasciculus and corticostriatal and thalamic pathways. Altered structural connectivity in the observed differential tractography results correlated with poor reading skills and phonological processing. Using a hodological approach, the current study provides novel evidence for the extent of the reading-related connectome and its aberrations in dyslexia. The results conform current functional neuroanatomical models of reading and developmental dyslexia but provide novel network-level and tract-level evidence on structural connectivity anomalies in dyslexia, including the vertical occipital fasciculus.

Structural white matter connectometry of word production in aphasia: an observational study.

While current dual-steam neurocognitive models of language function have coalesced around the view that distinct neuroanatomical networks subserve semantic and phonological processing, respectively, the specific white matter components of these networks remain a matter of debate. To inform this debate, we investigated relationships between structural white matter connectivity and word production in a cross-sectional study of 42 participants with aphasia due to unilateral left hemisphere stroke. Specifically, we reconstructed a local connectome matrix for each participant from diffusion spectrum imaging data and regressed these matrices on indices of semantic and phonological ability derived from their responses to a picture-naming test and a computational model of word production. These connectometry analyses indicated that both dorsally located (arcuate fasciculus) and ventrally located (inferior frontal-occipital, uncinate, and middle longitudinal fasciculi) tracts were associated with semantic ability, while associations with phonological ability were more dorsally situated, including the arcuate and middle longitudinal fasciculi. Associations with limbic pathways including the posterior cingulum bundle and the fornix were also found. All analyses controlled for total lesion volume and all results showing positive associations obtained false discovery rates < 0.05. These results challenge dual-stream accounts that deny a role for the arcuate fasciculus in semantic processing, and for ventral-stream pathways in language production. They also illuminate limbic contributions to both semantic and phonological processing for word production.

White-Matter Neuroanatomical Predictors of Aphasic Verb Retrieval.

Background: Current neurocognitive models of language function have been primarily built from evidence regarding object naming, and their hypothesized white-matter circuit mechanisms tend to be coarse grained. Methods: In this cross-sectional, observational study, we used novel correlational tractography to assess the white-matter circuit mechanism behind verb retrieval, measured through action picture-naming performance in adults with chronic aphasia. Results: The analysis identified tracts implicated in current neurocognitive dual-stream models of language function, including the left inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and arcuate fasciculus. However, the majority of tracts associated with verb retrieval were not ones included in dual-stream models of language function. Instead, they were projection pathways that connect frontal and parietal cortices to subcortical regions associated with motor functions, including the left corticothalamic pathway, frontopontine tract, parietopontine tract, corticostriatal pathway, and corticospinal tract. Conclusions: These results highlight that corticosubcortical projection pathways implicated in motor functions may be importantly related to language function. This finding is consistent with grounded accounts of cognition and may furthermore inform neurocognitive models. Impact statement This study suggests that in addition to traditional dual-stream language fiber tracts, the integrity of projection pathways that connect frontal and parietal cortices to subcortical motor regions may be critically associated with verb-retrieval impairments in adults with aphasia. This finding challenges neurological models of language function.