White matter network underlying semantic processing: evidence from stroke patients.

The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.

Distinct parallel activation and interaction between dorsal and ventral pathways during phonological and semantic processing: A cTBS-fMRI study.

Successful visual word recognition requires the integration of phonological and semantic information, which is supported by the dorsal and ventral pathways in the brain. However, the functional specialization or interaction of these pathways during phonological and semantic processing remains unclear. Previous research has been limited by its dependence on correlational functional magnetic resonance imaging (fMRI) results or causal validation using patient populations, which are susceptible to confounds such as plasticity and lesion characteristics. To address this, the present study employed continuous theta-burst stimulation combined with fMRI in a within-subject design to assess rapid adaptation in regional activity and functional connectivity of the dorsal and ventral pathways during phonological and semantic tasks. This assessment followed the precise inhibition of the left inferior parietal lobule and anterior temporal lobe in the dorsal and ventral pathways, respectively. Our results reveal that both the dorsal and ventral pathways were activated during phonological and semantic processing, while the adaptation activation and interactive network were modulated by the task type and inhibited region. The two pathways exhibited interconnectivity in phonological processing, and disruption of either pathway led to rapid adaptation across both pathways. In contrast, only the ventral pathway exhibited connectivity in semantic processing, and disruption of this pathway alone resulted in adaptive effects primarily in the ventral pathway. These findings provide essential evidence supporting the interactive theory, phonological information processing in particular, potentially providing meaningful implications for clinical populations.

Mechanisms underlying category learning in the human ventral occipito-temporal cortex.

The human ventral occipito-temporal cortex (VOTC) has evolved into specialized regions that process specific categories, such as words, tools, and animals. The formation of these areas is driven by bottom-up visual and top-down nonvisual experiences. However, the specific mechanisms through which top-down nonvisual experiences modulate category-specific regions in the VOTC are still unknown. To address this question, we conducted a study in which participants were trained for approximately 13 h to associate three sets of novel meaningless figures with different top-down nonvisual features: the wordlike category with word features, the non-wordlike category with nonword features, and the visual familiarity condition with no nonvisual features. Pre- and post-training functional MRI (fMRI) experiments were used to measure brain activity during stimulus presentation. Our results revealed that training induced a categorical preference for the two training categories within the VOTC. Moreover, the locations of two training category-specific regions exhibited a notable overlap. Remarkably, within the overlapping category-specific region, training resulted in a dissociation in activation intensity and pattern between the two training categories. These findings provide important insights into how different nonvisual categorical information is encoded in the human VOTC.

Hemispheric lateralization of language processing: insights from network-based symptom mapping and patient subgroups.

The hemispheric laterality of language processing has become a hot topic in modern neuroscience. Although most previous studies have reported left-lateralized language processing, other studies found it to be bilateral. A previous neurocomputational model has proposed a unified framework to explain that the above discrepancy might be from healthy and patient individuals. This model posits an initial symmetry but imbalanced capacity in language processing for healthy individuals, with this imbalance contributing to language recovery disparities following different hemispheric injuries. The present study investigated this model by analyzing the lateralization patterns of language subnetworks across multiple attributes with a group of 99 patients (compared to nonlanguage processing) and examining the lateralization patterns of language subnetworks in subgroups with damage to different hemispheres. Subnetworks were identified using a whole-brain network-based lesion-symptom mapping method, and the lateralization index was quantitatively measured. We found that all the subnetworks in language processing were left-lateralized, while subnetworks in nonlanguage processing had different lateralization patterns. Moreover, diverse hemisphere-injury subgroups exhibited distinct language recovery effects. These findings provide robust support for the proposed neurocomputational model of language processing.

Developmental plasticity of the structural network of the occipital cortex in congenital blindness.

The occipital cortex is the visual processing center in the mammalian brain. An unanswered scientific question pertains to the impact of congenital visual deprivation on the development of various profiles within the occipital network. To address this issue, we recruited 30 congenitally blind participants (8 children and 22 adults) as well as 31 sighted participants (10 children and 21 adults). Our investigation focused on identifying the gray matter regions and white matter connections within the occipital cortex, alongside behavioral measures, that demonstrated different developmental patterns between blind and sighted individuals. We discovered significant developmental changes in the gray matter regions and white matter connections of the occipital cortex among blind individuals from childhood to adulthood, in comparison with sighted individuals. Moreover, some of these structures exhibited cognitive functional reorganization. Specifically, in blind adults, the posterior occipital regions (left calcarine fissure and right middle occipital gyrus) showed reorganization of tactile perception, and the forceps major tracts were reorganized for braille reading. These plastic changes in blind individuals may be attributed to experience-dependent neuronal apoptosis, pruning, and myelination. These findings provide valuable insights into the longitudinal neuroanatomical and cognitive functional plasticity of the occipital network following long-term visual deprivation.

Functional connectome through the human life span.

The functional connectome of the human brain represents the fundamental network architecture of functional interdependence in brain activity, but its normative growth trajectory across the life course remains unknown. Here, we aggregate the largest, quality-controlled multimodal neuroimaging dataset from 119 global sites, including 33,809 task-free fMRI and structural MRI scans from 32,328 individuals ranging in age from 32 postmenstrual weeks to 80 years. Lifespan growth charts of the connectome are quantified at the whole cortex, system, and regional levels using generalized additive models for location, scale, and shape. We report critical inflection points in the non-linear growth trajectories of the whole-brain functional connectome, particularly peaking in the fourth decade of life. Having established the first fine-grained, lifespan-spanning suite of system-level brain atlases, we generate person-specific parcellation maps and further show distinct maturation timelines for functional segregation within different subsystems. We identify a spatiotemporal gradient axis that governs the life-course growth of regional connectivity, transitioning from primary sensory cortices to higher-order association regions. Using the connectome-based normative model, we demonstrate substantial individual heterogeneities at the network level in patients with autism spectrum disorder and patients with major depressive disorder. Our findings shed light on the life-course evolution of the functional connectome and serve as a normative reference for quantifying individual variation in patients with neurological and psychiatric disorders.

Cognitive Training Effect and Imaging Evidence.

Cognitive intervention is a specific form of non-pharmacological intervention used to combat cognitive dysfunction. In this chapter, behavioral and neuroimaging studies about cognitive interventions are introduced. Regarding intervention studies, the form of intervention and the effects of the interventions have been systematically sorted out. In addition, we compared the effects of different intervention approaches, which help people with different cognitive states to choose appropriate intervention programs. With the development of imaging technology, many studies have discussed the neural mechanism of cognitive intervention training and the effects of cognitive intervention from the perspective of neuroplasticity. Behavioral studies and neural mechanism studies are used to improve the understanding of cognitive interventions for the treatment of cognitive impairment.

Chinese character unitization enhances item memory in addition to associative memory: Evidence from ERP and TFR.

While the effect of unitization on associative memory has been established, its effect on item memory remains debated. This study aimed to investigate the influence of unitization on item memory using Chinese characters to manipulate unitization and recording scalp EEG to elucidate the underlying neural mechanisms. In the learning phase, participants were asked to determine whether the character pairs presented could form a Chinese compound character. In the subsequent testing phase, participants performed item recognition and associative recognition tasks. Behavioral results revealed that unitization not only improved associative memory but also facilitated item memory. Event-related potential analysis indicated there were FN400 effect (related to familiarity) and LPC effect (related to recollection) during associative recognition after unitization, however, only the LPC effect was observed for the item recognition. More importantly, time-frequency analysis demonstrated stronger θ oscillations (associated with recollection) in the unitized condition compared to the non-unitized condition, which further partially mediated the reduction in RT during the item recognition. These results suggest that unitization enhances item memory through recollection, thereby leading to more confident recognition judgments, and that unitization does not impair item processing within an association but rather enables more precise and accurate processing.

Functional and structural network changes related with cognition in semantic dementia longitudinally.

Longitudinal changes in the white matter/functional brain networks of semantic dementia (SD), as well as their relations with cognition remain unclear. Using a graph-theoretic method, we examined the neuroimaging (T1, diffusion tensor imaging, functional MRI) network properties and cognitive performance in processing semantic knowledge of general and six modalities (i.e., object form, color, motion, sound, manipulation and function) from 31 patients (at two time points with an interval of 2 years) and 20 controls (only at baseline). Partial correlation analyses were carried out to explore the relationships between the network changes and the declines of semantic performance. SD exhibited aberrant general and modality-specific semantic impairment, and gradually worsened over time. Overall, the brain networks showed a decreased global and local efficiency in the functional network organization but a preserved structural network organization with a 2-year follow-up. With disease progression, both structural and functional alterations were found to be extended to the temporal and frontal lobes. The regional topological alteration in the left inferior temporal gyrus (ITG.L) was significantly correlated with general semantic processing. Meanwhile, the right superior temporal gyrus and right supplementary motor area were identified to be associated with color and motor-related semantic attributes. SD manifested disrupted structural and functional network pattern longitudinally. We proposed a hub region (i.e., ITG.L) of semantic network and distributed modality-specific semantic-related regions. These findings support the hub-and-spoke semantic theory and provide targets for future therapy.

The influence of visual deprivation on the development of the thalamocortical network: Evidence from congenitally blind children and adults.

The thalamus is heavily involved in relaying sensory signals to the cerebral cortex. A relevant issue is how the deprivation of congenital visual sensory information modulates the development of the thalamocortical network. The answer is unclear because previous studies on this topic did not investigate network development, structure-function combinations, and cognition-related behaviors in the same study. To overcome these limitations, we recruited 30 congenitally blind subjects (8 children, 22 adults) and 31 sighted subjects (10 children, 21 adults), and conducted multiple analyses [i.e., gray matter volume (GMV) analysis using the voxel-based morphometry (VBM) method, resting-state functional connectivity (FC), and brain-behavior correlation]. We found that congenital blindness elicited significant changes in the development of GMV in visual and somatosensory thalamic regions. Blindness also resulted in significant changes in the development of FC between somatosensory thalamic regions and visual cortical regions as well as advanced information processing regions. Moreover, the somatosensory thalamic regions and their FCs with visual cortical regions were reorganized to process high-level tactile language information in blind individuals. These findings provide a refined understanding of the neuroanatomical and functional plasticity of the thalamocortical network.

Association between Changes in White Matter Microstructure and Cognitive Impairment in White Matter Lesions.

This study investigated the characteristics of cognitive impairment in patients with white matter lesions (WMLs) caused by cerebral small vessel disease and the corresponding changes in WM microstructures. Diffusion tensor imaging (DTI) data of 50 patients with WMLs and 37 healthy controls were collected. Patients were divided into vascular cognitive impairment non-dementia and vascular dementia groups. Tract-based spatial statistics showed that patients with WMLs had significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values throughout the WM areas but predominately in the forceps minor, forceps major (FMA), bilateral corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus (ILF), and anterior thalamic radiation, compared to the control group. These fiber bundles were selected as regions of interest. There were significant differences in the FA, MD, AD, and RD values (p < 0.05) between groups. The DTI metrics of all fiber bundles significantly correlated with the Montreal Cognitive Assessment (p < 0.05), with the exception of the AD values of the FMA and ILF. Patients with WMLs showed changes in diffusion parameters in the main WM fiber bundles. Quantifiable changes in WM microstructure are the main pathological basis of cognitive impairment, and may serve as a biomarker of WMLs.

The Neural Basis of Semantic Prediction in Sentence Comprehension.

Although prediction plays an important role in language comprehension, its precise neural basis remains unclear. This fMRI study investigated whether and how semantic-category-specific and common cerebral areas are recruited in predictive semantic processing during sentence comprehension. We manipulated the semantic constraint of sentence contexts, upon which a tool-related, a building-related, or no specific category of noun is highly predictable. This noun-predictability effect was measured not only over the target nouns but also over their preceding transitive verbs. Both before and after the appearance of target nouns, left anterior supramarginal gyrus was specifically activated for tool-related nouns and left parahippocampal place area was activated specifically for building-related nouns. The semantic-category common areas included a subset of left inferior frontal gyrus during the anticipation of incoming target nouns (activity enhancement for high predictability) and included a wide spread of areas (bilateral inferior frontal gyrus, left superior/middle temporal gyrus, left medial pFC, and left TPJ) during the integration of actually perceived nouns (activity reduction for high predictability). These results indicated that the human brain recruits fine divisions of cortical areas to distinguish different semantic categories of predicted words, and anticipatory semantic processing relies, at least partially, on top-down prediction conducted in higher-level cortical areas.

White matter network of oral word reading identified by network-based lesion-symptom mapping.

Oral word reading is supported by a neural subnetwork that includes gray matter regions and white matter tracts connected by the regions. Traditional methods typically determine the reading-relevant focal gray matter regions or white matter tracts rather than the reading-relevant global subnetwork. The present study developed a network-based lesion-symptom mapping (NLSM) method to identify the reading-relevant global white matter subnetwork in 84 brain-damaged patients. The global subnetwork was selected among all possible subnetworks because its global efficiency exhibited the best explanatory power for patients' reading scores. This reading subnetwork was left lateralized and included 7 gray matter regions and 15 white matter tracts. Moreover, the reading subnetwork had additional explanatory power for the patients' reading performance after eliminating the effects of reading-related local regions and tracts. These findings refine the reading neuroanatomical architecture and indicate that the NLSM can be a better method for revealing behavior-specific subnetworks.

Early top-down modulation in visual word form processing: Evidence from an intracranial SEEG study.

Visual word recognition, at a minimum, involves the processing of word form and lexical information. Opinions diverge on the spatiotemporal distribution of and interaction between the two types of information. Feedforward theory argues that they are processed sequentially, while interactive theory advocates that lexical information is processed fast and modulates early word form processing. To distinguish the two theories, we applied stereoelectroencephalography (SEEG) to 33 human adults with epilepsy (25 males and 8 females) during visual lexical decisions. The stimuli included real words (RWs), pseudowords (PWs) with legal radical positions, nonwords (NWs) with illegal radical positions, and stroked-changed words (SWs) in Chinese. Word form and lexical processing were measured by the word form effect (PW vs. NW) and lexical effect (RW vs. PW), respectively. Gamma-band (60 ∼ 140 Hz) SEEG activity was treated as an electrophysiological measure. A word form effect was found in eight left brain regions (i.e., the inferior parietal lobe, insula, fusiform, inferior temporal, middle temporal, middle occipital, precentral and postcentral gyri) from 50 ms poststimulus onset, while a lexical effect was observed in five left brain regions (i.e., the calcarine, middle temporal, superior temporal, precentral and postcentral gyri) from 100 ms poststimulus onset. The two effects overlapped in the precentral (300 ∼ 500 ms) and postcentral (100 ∼ 200 ms and 250 ∼ 600 ms) gyri. Moreover, high-level regions provide early feedback to word form regions. These results demonstrate that lexical processing occurs early and modulates word form recognition, providing vital supportive evidence for interactive theory.SIGNIFICANCE STATEMENTA pivotal unresolved dispute in the field of word processing is whether word form recognition is obligatorily modulated by high-level lexical top-down information. To address this issue, we applied intracranial stereoelectroencephalography (SEEG) to 33 adults with epilepsy, to precisely delineate the spatiotemporal dynamics between processing word form and lexical information during visual word recognition. We observed that lexical processing occurred from 100 ms poststimulus presentation and even spatiotemporally overlapped with word form processing. Moreover, the high-order regions provided feedback to the word form regions in the early stage of word recognition. These results revealed the crucial role of high-level lexical information in word form recognition, deepening our understanding of the functional coupling among brain regions in word processing networks.

Domain-specific functional coupling between dorsal and ventral systems during action perception.

Visual perception of actions and objects has been shown to activate different cortical systems: action perception system spanning more dorsally, across parietal, frontal, and dorsal temporal regions; object perception relying more strongly the ventral occipitotemporal cortex (VOTC). Compared to the well-established object-domain structure (e.g., faces vs. artifacts) in VOTC, it is less known whether the action perception system is constrained by similar domain principle and whether it communicates with the ventral object recognition system in a domain-specific manner. In a fMRI long-block experiment designed to evaluate both regional activity and task-based functional connectivity (FC) patterns, participants viewed animated videos of a human performing two domains of actions to the same set of meaningless shapes without object-domain information: social-communicative-actions (e.g., waving) and manipulation-actions (e.g., folding). We observed action-domain-specific activations, with the superior temporal sulcus and the right precentral region responding more strongly during social-communicative-action perception; the supramarginal gyrus, inferior and superior parietal lobe, and precentral gyrus during manipulation-action perception. The two domains of action perception systems communicated with VOTC in domain-specific manners: FC between the social-communicative-action system and the bilateral fusiform face area was enhanced during social-communicative-action perception; FC between the manipulation-action system and the left tool-preferring lateral occipitoptemporal cortex was enhanced during manipulation-action perception. There was a significant correlation between the FC-with-action-system and the local activity strength across VOTC voxels. Our findings highlight social- and manipulation-domains of human interaction as an overarching principle of both object and action perception systems, with domain-based functional communication across systems.

Characteristics of Non-linguistic Cognitive Impairment in Post-stroke Aphasia Patients.

Background: Non-linguistic cognitive training has been suggested to improve the communication skills of patients with post-stroke aphasia (PSA). However, the association between language and non-linguistic cognitive functions is not fully understood. In this study, we used the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) to evaluate the characteristics of non-linguistic cognitive impairments in Chinese PSA patients. Methods: A total of 86 stroke patients were recruited in this study. Language and non-linguistic cognitive impairments were evaluated by the Western Aphasia Battery (WAB) and LOTCA, respectively. The patients were divided into two groups (PSA and non-PSA), and the Chinese norm (the data came from 44 Chinese individuals without neurological disorders in a previous study) was used as the control group. The LOTCA scores were compared among the three groups. Patients in the PSA group were subdivided into the fluent aphasia group (FAG) and the non-FAG according to the Chinese aphasia fluency characteristic scale. The LOTCA scores were also compared between the PSA subdivisions. Potential confounders were adjusted in the analysis of covariance. Partial correlation analysis between the subscores of WAB and LOTCA was also performed. Results: The total LOTCA scores in the PSA group (75.11 ± 17.08) were significantly lower compared with scores in the non-PSA (96.80 ± 7.75, P < 0.001) and the control group (97.65 ± 16.24, P < 0.001). The PSA group also had lower orientation, visual perception (VP), spatial perception (SP), visuomotor organization, thinking operation, and attention scores. The total LOTCA, orientation, VP, SP, and MP scores were lower in the non-FAG (69.24 ± 18.06, 8.62 ± 5.09, 12.76 ± 2.47, 7.48 ± 3.01, and 9.62 ± 2.25, respectively) compared with the FAG (80.36 ± 14.07, 12.14 ± 3.99, 14.09 ± 1.93, 9.68 ± 3.01, 10.55 ± 1.63, respectively, P's < 0.05). The aphasia quotient was positively correlated with the total score of LOTCA and scores of orientation, VP, SP, and MP (r = 0.710, 0.744, 0.565, 0.597, and 0.616; P < 0.001). Conclusion: Compared with stroke patients without aphasia, patients with PSA often have more extensive and serious non-linguistic cognitive impairments. Patients with non-fluent aphasia often present with serious cognitive impairments than those with fluent aphasia, especially the impairments of orientation and SP. Non-linguistic cognitive impairments correlate with language impairments in aphasia.

Altered Granger Causal Connectivity of Resting-State Neural Networks in Patients With Leukoaraiosis-Associated Cognitive Impairment-A Cross-Sectional Study.

Background: The purpose of this study was to provide an imaging reference for the measurement of disease progression, as well as to reveal the pathogenesis of leukoaraiosis (LA). Methods: Eighty-seven subjects were divided into three groups: LA patients with vascular dementia (LA-VaD) (20 subjects: 14 female, 6 male), LA patients with vascular cognitive impairment nondementia (LA-VCIND) (32 subjects: 14 male, 18 female), and normal controls (NC) (35 subjects: 14 male, 21 female). A multivariate Granger causality analysis (mGCA) was applied to the resting-state networks (RSNs) to evaluate the possible effective connectivity within the resting-state networks retrieved by independent component analysis (ICA) from resting-state functional magnetic resonance imaging (rs-fMRI) data. Results: Ten RSNs were identified: the primary visual network, secondary visual network, auditory network, sensorimotor network, anterior default mode network, posterior default mode network, salience network, dorsal attention network, left working memory network, and the right working memory network. Using independent component analysis, significant average Z scores were found in the anterior default mode network, salience network, dorsal attention network, and right working memory network between LA-VAD and NC groups. The functional connectivity (FC) strength of the networks was different between the NC, LA-VCIND, and LA-VaD groups. Effective connectivity between RSNs was compensated by either increased or decreased effective connectivity changes in these three groups. Conclusions: The components of resting-state networks kept changing as the disease progressed. Meanwhile, the activation intensity increased at the early stage of LA and decreased as patients' cognitive impairment aggravated. Furthermore, the direction and strength of connections between these networks changed and remodeled differently. These suggest that the human brain compensates for specific functional changes at different stages.

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer's Disease.

BACKGROUND: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer's disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. OBJECTIVE: To unravel mutual and divergent functional alterations in Alzheimer's disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer's disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17). METHODS: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis. RESULTS: Apart from differing connections between Alzheimer's disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes. CONCLUSION: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain's functional disconnectivity in Alzheimer's disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures.