Increased world knowledge in older adults does not prevent decline in world knowledge comprehension: An ERP study.

A meaningful sentence might not be sensible according to world knowledge. In aging, world knowledge continues to increase, but semantic processing declines. An intriguing question is whether increased world knowledge aids world knowledge comprehension, even in the face of declining semantic processing. The present study collected EEG data from 43 older and 43 younger adults as they read correct sentences, sentences with a semantic violation, and sentences with a world knowledge violation. Compared to younger adults, older adults had a significantly greater reduction in amplitude and delayed peak/onset latency of N400 for both semantic and world knowledge integration. A significant Group by Condition by Region interaction revealed that, although the N400 amplitude under the semantic violation condition was comparable to that under the world knowledge violation condition in younger adults, the N400 amplitude in the posterior brain region was significantly smaller under the world knowledge violation condition than under the semantic violation condition in older adults. The N400 difference between world knowledge and semantic violation conditions was negatively correlated only with vocabulary scores. In conclusion, age-related increases in world knowledge do not help older adults to comprehend world knowledge more effectively.

The effects of 7-week cognitive training in patients with vascular cognitive impairment, no dementia (the Cog-VACCINE study): A randomized controlled trial.

INTRODUCTION: Evidence for the efficacy of cognitive training in patients with subcortical vascular cognitive impairment no dementia is still lacking. METHODS: A randomized, active controlled design using multidomain, adaptive, computerized cognitive training for 30 minutes, 5 days/week for 7 weeks. Assessments included global cognitive function and executive function (primary outcomes) and brain functional connectivity and structural changes (secondary outcomes). RESULTS: Sixty patients were randomized across three medical centers in Beijing. At the end of the intervention, the cognitive training group showed significant improvement in Montreal Cognitive Assessment relative to the active control group (P = .013) and significantly increased functional connectivity between the left dorsolateral prefrontal cortex and medial prefrontal cortex, which was significantly correlated with Montreal Cognitive Assessment change (P = .017). DISCUSSION: Computerized cognitive training significantly improved global cognitive function, which was supported by the improved brain plasticity. Incorporation of biomarkers should be implemented in cognitive training trials.

Separate Brain Circuits Support Integrative and Semantic Priming in the Human Language System.

Semantic priming is a crucial phenomenon to study the organization of semantic memory. A novel type of priming effect, integrative priming, has been identified behaviorally, whereby a prime word facilitates recognition of a target word when the 2 concepts can be combined to form a unitary representation. We used both functional and anatomical imaging approaches to investigate the neural substrates supporting such integrative priming, and compare them with those in semantic priming. Similar behavioral priming effects for both semantic (Bread-Cake) and integrative conditions (Cherry-Cake) were observed when compared with an unrelated condition. However, a clearly dissociated brain response was observed between these 2 types of priming. The semantic-priming effect was localized to the posterior superior temporal and middle temporal gyrus. In contrast, the integrative-priming effect localized to the left anterior inferior frontal gyrus and left anterior temporal cortices. Furthermore, fiber tractography showed that the integrative-priming regions were connected via uncinate fasciculus fiber bundle forming an integrative circuit, whereas the semantic-priming regions connected to the posterior frontal cortex via separated pathways. The results point to dissociable neural pathways underlying the 2 distinct types of priming, illuminating the neural circuitry organization of semantic representation and integration.

Reduced frontal cortex efficiency is associated with lower white matter integrity in aging.

Increased frontal cortex activation during cognitive task performance is common in aging but remains poorly understood. Here we explored patterns of age-related frontal brain activations under multiple task performance conditions and their relationship to white matter (WM) microstructure. Groups of younger (N = 28) and older (N = 33) participants completed a task-switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging was performed. Results from fMRI analyses indicated age-related increases in frontal brain activations under conditions of poorer performance in the older group (the nonswitch and switch conditions) and for a contrast in which behavioral performance was equated (older group nonswitch condition vs. younger group switch condition). Within the older adult group, higher frontal activation was associated with poorer behavioral performance under all task conditions. In 2 regions in right frontal cortex, blood oxygen level-dependent (BOLD) magnitudes were negatively correlated with WM integrity in tracts connecting these structures with other task-relevant frontoparietal and striatal regions. Our results link age-related declines in the efficiency of frontal cortex functioning with lower WM integrity in aging.

Dynamic brain architectures in local brain activity and functional network efficiency associate with efficient reading in bilinguals.

The human brain is organized as a dynamic network, in which both regional brain activity and inter-regional connectivity support high-level cognitive processes, such as reading. However, it is still largely unknown how the functional brain network organizes to enable fast and effortless reading processing in the native language (L1) but not in a non-proficient second language (L2), and whether the mechanisms underlying local activity are associated with connectivity dynamics in large-scale brain networks. In the present study, we combined activation-based and multivariate graph-theory analysis with functional magnetic resonance imaging data to address these questions. Chinese-English unbalanced bilinguals read narratives for comprehension in Chinese (L1) and in English (L2). Compared with L2, reading in L1 evoked greater brain activation and recruited a more globally efficient but less clustered network organization. Regions with both increased network efficiency and enhanced brain activation in L1 reading were mostly located in the fronto-temporal reading-related network (RN), whereas regions with decreased global network efficiency, increased clustering, and more deactivation in L2 reading were identified in the default mode network (DMN). Moreover, functional network efficiency was closely associated with local brain activation, and such associations were also modulated by reading efficiency in the two languages. Our results demonstrate that an economical and integrative brain network topology is associated with efficient reading, and further reveal a dynamic association between network efficiency and local activation for both RN and DMN. These findings underscore the importance of considering interregional connectivity when interpreting local BOLD signal changes in bilingual reading.

Left middle temporal and inferior frontal regions contribute to speed of lexical decision: a TMS study.

Activation of left anterior inferior frontal gyrus (aLIFG) and left middle temporal gyrus (LMTG) has been observed in some functional neuroimaging studies of lexical decision but not others. It is thus unclear whether these two regions are necessary for word recognition. By applying continuous theta-burst transcranial magnetic stimulation (TMS) which temporally suppresses local brain function, we examined whether aLIFG and LMTG play causal roles in word recognition in a visual lexical decision task (LDT). Furthermore, we manipulated stimulus onset asynchrony (SOA) between prime and target to test whether these regions contribute to word recognition differently. In the LDT task, target words were preceded by semantically related primes (Related Condition; RC) or semantically unrelated words (Unrelated Condition; UC), under both short (150 ms) and long (600 ms) SOA conditions. TMS of aLIFG and LMTG significantly affected the word recognition speed compared to TMS of Vertex. Our results provide evidence that both aLIFG and LMTG contribute to word recognition speed. Furthermore, at short SOA, TMS of aLIFG or LMTG prolonged reaction time (RT). In contrast, at long SOA, there was a significant region by SOA by TMS interaction such that TMS of aLIFG prolonged RT, whereas TMS of LMTG speeded RT. These results suggest that aLIFG and LMTG may play different roles in word recognition.

Effects of computerized cognitive training on functional brain networks in patients with vascular cognitive impairment and no dementia.

AIMS: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention-related cognitive improvement. This study provides comprehensive research on the changes in intra- and inter-brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. METHODS: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7-week training, and at the 6-month follow-up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra- and inter-network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. RESULTS: We found significantly decreased intra-network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra-LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. CONCLUSIONS: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies.

The role of the left prefrontal cortex in sentence-level semantic integration.

Whether left inferior frontal gyrus (LIFG) activation during sentence comprehension reflects semantic integration or domain-general cognitive control remains unclear. To address this issue, 26 participants were presented with sentences word by word during fMRI scanning and were asked to perform two semantic tasks, one explicit (semantic congruency judgment) and one implicit (font size judgment). In the two language tasks, semantic integration load was parametrically manipulated with high cloze, low cloze and semantically violated sentences. Participants also performed a classical Stroop task during scanning. Conjunction analysis of the explicit and implicit tasks revealed two regions in left inferior frontal gyrus associated with semantic integration load: one anterior region (aIFG) and one posterior region (pIFG). However, only the pIFG region was also activated during the Stroop task. These results indicate that different regions in the LIFG play different roles in semantic integration, with aIFG more important for domain-specific processing and pIFG more important for domain-general cognitive control.

The anterior left inferior frontal gyrus contributes to semantic unification.

Semantic unification, the process by which small blocks of semantic information are combined into a coherent utterance, has been studied with various types of tasks. However, whether the brain activations reported in these studies are attributed to semantic unification per se or to other task-induced concomitant processes still remains unclear. The neural basis for semantic unification in sentence comprehension was examined using event-related potentials (ERP) and functional Magnetic Resonance Imaging (fMRI). The semantic unification load was manipulated by varying the goodness of fit between a critical word and its preceding context (in high cloze, low cloze and violation sentences). The sentences were presented in a serial visual presentation mode. The participants were asked to perform one of three tasks: semantic congruency judgment (SEM), silent reading for comprehension (READ), or font size judgment (FONT), in separate sessions. The ERP results showed a similar N400 amplitude modulation by the semantic unification load across all of the three tasks. The brain activations associated with the semantic unification load were found in the anterior left inferior frontal gyrus (aLIFG) in the FONT task and in a widespread set of regions in the other two tasks. These results suggest that the aLIFG activation reflects a semantic unification, which is different from other brain activations that may reflect task-specific strategic processing.

The social hierarchical restrictions of Chinese verbs rapidly guide online thematic role assignment in comprehension.

The information about social hierarchical relationship has been intrinsically embedded into semantic restrictions of some Chinese verbs theoretically. For example, the Chinese verb ''(shanyang, support: provide for the needs and comfort of one's elders) only allows its Agent role to have a lower social status compared to the Patient role. However, whether this hierarchical restriction can be rapidly activated and how it impacts online thematic role assignment in reading remains to be seen. To answer this question, a 2 (Verb Type: hierarchical vs non-hierarchical verbs) × 2 (Social Hierarchy Sequence: match vs mismatch) design was constructed in the present study to investigate the interaction between the two factors. ERPs showed that hierarchical restriction violations evoked a stronger anterior negativity to the sentence-final noun (NP2). This effect was absent under two non-hierarchical conditions. To our knowledge, this study is the first to reveal that social hierarchical restrictions of Chinese hierarchical verbs can be rapidly available to guide online thematic role assignment and this process might be closely related to readers' thematic role knowledge.

Processing speed mediates the relationship between brain structure and semantic fluency in aging.

The present study has investigated how brain structure and processing speed contribute to age-related changes in semantic fluency. Groups of younger (N = 37) and older healthy participants (N = 40) completed a semantic fluency test and digit symbol test, and rested while diffusion tensor imaging (DTI) was performed. Group comparisons and correlational analysis revealed that age-related decline in semantic fluency was associated with reduction in gray matter volume in widespread fronto-temporal regions. Age-related decline in semantic fluency was also associated with decline in white matter integrity in brain tracts connecting these brain regions. Critically, hierarchical regression analysis suggested that low processing speed fully mediated the negative effects of lower gray matter volume and white matter integrity on semantic fluency. The present findings provide a support for the processing speed theory in relation to age related decline in semantic fluency, and also provide a reference for improving cognitive decline.

Improvement in language function in patients with aphasia using computer-assisted executive function training: A controlled clinical trial.

BACKGROUND: Nonverbal cognitive training for aphasia has gained popularity. Prior research has found that cognitive status correlates with language function. OBJECTIVE: To determine whether nonverbal computer-assisted executive control training (CAET) to improve cognitive status affects language performance in patients with aphasia (PWA) and executive dysfunction. DESIGN: A single blind randomized trial. SETTING: Department of Rehabilitation, Affiliated Hospital of Xuzhou Medical University. PARTICIPANTS: A total of 68 individuals were randomized, underwent treatment and were included in the analysis (CAET group, n = 33; control group, n = 35). INTERVENTIONS: The experimental group was treated with 4 weeks of traditional speech and language therapy (SLT) combined with CAET. The control group underwent SLT only. MAIN OUTCOME MEASURES: Western Aphasia Battery [WAB]) with executive dysfunction (as assessed by the verbal fluency test [VFT], the Proverbs Test, the Tower of London Test [TLT], the Stroop Color and Word Test [SCWT], and the Trail Making Test [TMT]). RESULTS: Differences between pre- and posttreatment language outcomes except oral naming (group × time, p = .236) were significantly greater in the experimental group compared with the control group: spontaneous speech (group × time, p = .026), auditory comprehension (group × time, p < .001), speech repetition (group × time, p = .001), and aphasia quotient (AQ; group × time, p < .001). A similar effect was observed for cognitive function such as Trial Making Test (TMT)-A (group × time, p = .006), TMT-B (group × time, p = .005), and verbal fluency test (VFT-V; group × time, p = .018). CONCLUSION: The study demonstrates that CAET combined with SLT can yield favorable language outcomes for PWA, especially improvements in auditory comprehension and AQ. CAET combined with SLT generates benefits in both cognitive function and language performance.

Independent syntactic representation identified in left front-temporal cortex during Chinese sentence comprehension.

It has been well established that syntactic representation is independent of semantic representation in Indo-European languages, but it is unclear whether this is the case in Chinese. The present functional magnetic resonance imaging (fMRI) study adopted a syntactic priming paradigm to investigate the neural basis of Chinese syntactic representation. A passive sentence was preceded by either a passive or an active sentence without repeating a verb or a pattern of agent-patient animacy, thus constructing primed and unprimed sentence pairs based on sentence structure. The fMRI data were collected from 22 native Chinese speakers while they were reading the sentences. Priming-related activation suppression was found in the left temporal pole, left inferior frontal gyrus and left precentral gyrus. The results are the strongest neuroimaging evidence to date that syntactic representation is independent of semantic representation in Chinese, in line with Indo-European languages.

Morpho-semantic analysis of ambiguous morphemes in Chinese compound word recognition: An fMRI study.

The present fMRI study examined the neural basis of processing context-supported or -unsupported interpretations of ambiguous morphemes during Chinese compound word reading in a masked priming lexical decision task. Targets were Chinese bimorphemic words that contained ambiguous morphemes. Prime words contained the same ambiguous morphemes with either the same meanings (context-supported interpretation) or different ones (context-unsupported interpretation). Lexical-level semantic sharing and unrelated control conditions were also included. Compared to the unrelated control condition, the context-supported morphemic meaning was associated with increased activity in the left SFG and bilateral MTG, and this priming effect could be dissociated from that of the lexical-level semantic-related condition. In broader brain regions, including the left SFG, bilateral MTG, left STG, right IOG, and left precuneus, the context-unsupported meaning condition showed decreased activity compared with the unrelated control condition. These findings indicate that both the context-supported and -unsupported meanings evoke significant priming effects, however, they differ from each other with different brain basis, providing new insight into the neural substrates of ambiguous morpheme processing.

The Efficacy of COGnitive tRaining in patiEnts with Amnestic mild coGnitive impairmENT (COG-REAGENT): Protocol for a Multi-Center Randomized Controlled Trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is often the prodromal stage of Alzheimer's disease (AD). Although previous studies have suggested that computerized cognitive training is an effective non-pharmacological intervention for aMCI, large-sample, randomized controlled studies are warranted to provide a high level of evidence. OBJECTIVE: To identify the efficacy of computerized cognitive training for aMCI. METHODS: This study will include 260 patients diagnosed with aMCI from 8 centers in China. A computerized multi-domain adaptive training program will be used in this study, and the targeted cognitive domains include memory, attention, language, and executive function. The patients will be randomized into either a cognitive-training group or an active-control group. The intervention is a 12-week internet-based cognitive training performed for 40 minutes per day, 4 days a week. Neuropsychological assessments and structural and functional MRI will be obtained at baseline, at the end of the intervention, and 6 months after randomization. The primary outcome will be the global cognitive function score assessed by Montreal Cognitive Assessment. The secondary outcomes include changes in other neuropsychological assessments and neuroplasticity changes measured by structural and functional MRI. RESULTS: The trial is currently ongoing, and it is anticipated that recruitment will be completed in December 2020. CONCLUSION: This multi-center, large-sample, randomized controlled trial will investigate the short and long-term effects of computerized cognitive training in patients with aMCI. Furthermore, the combination of functional and structural MRI results will also reveal the underlying mechanisms of the effect of intervention.

Involvement of left inferior frontal gyrus in sentence-level semantic integration.

Using event-related functional MRI, we examined the involvement of the left inferior frontal gyrus (LIFG) in semantic integration in reading Chinese sentences. During scanning, Chinese readers read individually presented sentences and judged whether or not a sentence was semantically acceptable. Behaviorally, those sentences with a small degree of semantic violation were found to be more difficult to reject relative to sentences with a large degree of semantic violation, indicating that more semantic integration occurred in the former than in the latter condition. Direct contrast revealed significantly greater brain activity in the LIFG for sentences with a small violation, relative to those with a large violation, but no differences in any anterior temporal cortical areas between the two types of anomalous sentences. The results are in line with the idea that the LIFG plays a critical role in integrating individual word meanings to coherent sentence-level messages, but not with the idea that semantic integration depends on anterior temporal cortex in language comprehension.

Gray matter density negatively correlates with duration of heroin use in young lifetime heroin-dependent individuals.

Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based morphometry in 30 lifetime heroin-dependent individuals who had abstained from drug use for 5 months, and 34 healthy participants. The DGM of the prefrontal, temporal and cingulate cortices significantly decreased in heroin addicts relative to the healthy group. Critically, partial correlation analysis, which controlled for age, education and gender factors as well as nicotine use and heroin abstinence duration, showed that the duration of heroin use negatively correlated with the DGM in heroin-dependent individuals. These results provide compelling evidence for structural abnormality in heroin-dependent individuals and further suggest that duration of heroin use is a critical factor leading to brain damage.

Effect of cognitive training on episodic memory retrieval in amnestic mild cognitive impairment patients: study protocol for a clinical randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is a transition state between asymptomatic stage and dementia. Amnestic MCI (aMCI) patients who mainly present with memory deficits are highly likely to progress to Alzheimer's disease (AD). At present, no broadly effective drug therapy is available to prevent the progression from memory deficit to dementia. Cognitive control training, which has transfer effects on multiple cognitive capacities including memory function in healthy old adults, has not yet been applied to aMCI. METHODS/DESIGN: In this single-center, randomized double-blind placebo-controlled study, 70 aMCI patients will be recruited and randomly assigned to the training and control groups. The intervention is an Internet-based cognitive control training program performed for 30 min daily, five days per week, for 12 consecutive weeks. Neuropsychological assessment and structural and functional magnetic resonance imaging (MRI) will be performed at baseline and outcome. Primary outcomes are changes of episodic memory retrieval function. Secondary outcome measures are neuroplasticity changes measured by functional and structural MRI. DISCUSSION: In this study, an Internet-based cognitive control training program is adopted to investigate whether cognitive control training can enhance the retrieval of episodic memory in aMCI patients. The combination of multi-modal MRI and neuropsychological tests could have a good sensitivity in evaluating the effects of cognitive control training and could also uncover the underlying neural underpinning. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133052 . Registered on 21 April 2017.

Broca's area plays a role in syntactic processing during Chinese reading comprehension.

Event-related functional magnetic resonance imaging (ER-fMRI) was adopted to examine brain activation of syntactic processing in reading logographic Chinese. While fMRI data were obtained, 15 readers of Chinese read individually presented sentences and performed semantic congruency judgments on three kinds of sentences: Congruous sentences (CON), sentences with a semantic violation (SEM), and sentences with both semantic and syntactic violations (SEM+SYN). The two types of incongruous sentences were matched in the degree of semantic plausibility. Three brain regions were identified showing significantly different levels of percent signal change across the three conditions, including BA44 in the left inferior frontal gyrus (IFG) and both BA9 and BA10/46 in the left middle frontal gyrus (MFG). Furthermore, the mean percent signal change in the left BA44 observed in the SEM+SYN condition was significantly stronger than that in either the SEM or the CON condition, while the latter two conditions were at a similar level, implying an important role of this area in Chinese syntactic processing. These results, in conjunction with those found in alphabetic scripts, suggest that there are some common neural substrates underlie syntactic processing across distinctive writing systems such as the logographic Chinese and the alphabetic English.

Reduced Syntactic Processing Efficiency in Older Adults During Sentence Comprehension.

Researchers have frequently reported an age-related decline in semantic processing during sentence comprehension. However, it remains unclear whether syntactic processing also declines or whether it remains constant as people age. In the present study, 26 younger adults and 20 older adults were recruited and matched in terms of working memory, general intelligence, verbal intelligence and fluency. They were then asked to make semantic acceptability judgments while completing a Chinese sentence reading task. The behavioral results revealed that the older adults had significantly lower accuracy on measures of semantic and syntactic processing compared to younger adults. Event-related potential (ERP) results showed that during semantic processing, older adults had a significantly reduced amplitude and delayed peak latency of the N400 compared to the younger adults. During syntactic processing, older adults also showed delayed peak latency of the P600 relative to younger adults. Moreover, while P600 amplitude was comparable between the two age groups, larger P600 amplitude was associated with worse performance only in the older adults. Together, the behavioral and ERP data suggest that there is an age-related decline in both semantic and syntactic processing, with a trend toward lower efficiency in syntactic ability.