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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

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.

Semantic integration and working memory both decline with age. However, it remains unclear whether the semantic integration decline is independent of working memory decline or whether it can be solely explained by the latter factor. In this event-related potentials experiment, 43 younger adults and 43 cognitively healthy older adults read semantically congruent and incongruent sentences. After controlling for working memory, behavioral accuracy was significantly lower in the older adults than in the younger adults. In addition, the semantic integration related N400 effect (incongruent vs. congruent) for correct trials was apparent in the whole brain in the younger adults but restricted to the posterior region in the older adults. The results clarify the relationship between working memory and semantic integration, and clearly demonstrate that semantic integration decline is independent of working memory decline during aging.

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. Electronic supplementary material The online version of this article (10.1186/s13063-018-3143-0) contains supplementary material, which is available to authorized users.

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.

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.

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.

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.

The aim of the present study was to investigate whether age-related brain response alterations during sentence comprehension exist when verbal fluency and intelligence are controlled for. Twenty-four younger and twenty-four older adults with matched verbal fluency, verbal intelligence, years of education, and gender ratio were recruited. They were asked to read congruent (CON) and incongruent (INCON) sentences to make semantic acceptability judgments. A significant group by condition interaction on accuracy was found, showing a significant congruency effect in younger, but not older adults. The ERP results revealed a dynamic temporal-spatial change in older adults. The congruency related N400 effect was reduced and delayed significantly in the older adults compared to the younger adults, and accompanied by different distribution patterns across time windows. The late positive component with more positive-going in the INCON condition than the CON condition was found in older adults only, which did not correlate with the performance, however. The results suggest that with age, there is a decline in semantic processing during sentence comprehension.

SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 121 kb)

Contains fulltext : 207578.pdf (Publisher’s version ) (Closed access) Semantic unification during sentence comprehension has been associated with amplitude change of the N400 in event-related potential (ERP) studies, and activation in the left inferior frontal gyrus (IFG) in functional magnetic resonance imaging (fMRI) studies. However, the specificity of this activation to semantic unification remains unknown. To more closely examine the brain processes involved in semantic unification, we employed simultaneous EEG-fMRI to time-lock the semantic unification related N400 change, and integrated trial-by-trial variation in both N400 and BOLD change beyond the condition-level BOLD change difference measured in traditional fMRI analyses. Participants read sentences in which semantic unification load was parametrically manipulated by varying cloze probability. Separately, ERP and fMRI results replicated previous findings, in that semantic unification load parametrically modulated the amplitude of N400 and cortical activation. Integrated EEG-fMRI analyses revealed a different pattern in which functional activity in the left IFG and bilateral supramarginal gyrus (SMG) was associated with N400 amplitude, with the left IFG activation and bilateral SMG activation being selective to the condition-level and trial-level of semantic unification load, respectively. By employing the EEG-fMRI integrated analyses, this study among the first sheds light on how to integrate trial-level variation in language comprehension. 12 p.

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.

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.

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.

Older adults often show different functional activation patterns than younger adults in prefrontal cortex (PFC) when performing cognitive control tasks. These differences include age-related increases in PFC activation magnitude and reorganized PFC functional connectivity patterns. However, it remains unclear whether age-related alterations in brain activation patterns reflect a positive mechanism (e.g. compensatory response) or a sign of brain dysfunction (e.g. reduced efficiency). Here we used functional magnetic resonance imaging (fMRI) to compare PFC activation magnitudes and PFC connectivity patterns between younger and older adult groups during performance of a task switching paradigm. Results indicated age-related increases both in PFC activation magnitudes and in PFC functional connectivity with inferotemporal (IT) regions. However, these age-related fMRI increases were differentially associated with task performance. Whereas increased PFC activation magnitudes tended to be either unrelated to task RT or associated with poorer task performance, increased PFC-IT connectivity was associated with better task performance in older adults. Our results provide new evidence suggesting that mechanisms subserving age-related reductions in efficiency and successful compensation can coexist in older adults in the context of the same task.

Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.

The relationship between impulsivity and cognitive control is still unknown. We hypothesized that trait impulsivity would differentially correlate with specific cognitive control processes. Trait impulsivity was measured by the Barratt Impulsiveness Scale, which assesses motor, attention, and non-planning impulsiveness components. Cognitive control was measured by a hybrid-designed Stroop task, which distinguishes proactive and reactive control. Thirty-three participants performed the Stroop task while they were scanned by functional magnetic resonance imaging. Proactive and reactive control involved increased activity in the fronto-parietal network, and brain activity was associated with impulsivity scores. Specifically, higher motor impulsiveness was associated with a larger proactive control effect in the inferior parietal lobule and a smaller reactive control effect in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate contex. Higher attention impulsivity was associated with a smaller proactive control effect in the right DLPFC. Such a correlation pattern suggests that impulsivity trait components are attributable to different cognitive control subsystems.

While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC) and low cloze (LC) probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC) was found in several regions, especially the left middle frontal gyrus (MFG) and right inferior frontal gyrus (IFG), which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ 42 and Aβ 42 /p-Tau 181 ) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ 42 /p-Tau 181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.

To investigate the functional significance of the late positive complex (LPC) in the Stroop task, the present study recruited 22 participants and had them report the color of words in the classical Stroop task and the rotation state of words in a Rotation judgment task. Color words whose ink color was either congruent (CON) or incongruent (INCON) with the word's meaning were presented in both tasks. Consistent with previous studies, the N450 and LPC were observed in the Stroop task, accompanied by slowed reaction time (RT) in the INCON condition compared with the CON condition. Notably, a larger LPC was observed in the INCON condition than in the CON condition in the Rotation task, while RT and accuracy were comparable between the two conditions. Because the incongruence between ink color and word meaning was independent from the response, and neither influenced accuracy nor RT in the Rotation task, the results suggested that the LPC may have resulted from the perceptual conflict between ink color and word meaning.

Background Vascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that fall short of a dementia diagnosis. There is currently no treatment for VCIND. Computerized cognitive training, which has significantly improved cognitive function in healthy older adults and patients with cognitive impairment has not yet been applied to VCIND. Methods/Design The proposed study is a three-center, double-blinded, randomized controlled trial that will include 60 patients with VCIND. The patients will be randomized to either a training or a control group. The intervention is internet-based cognitive training performed for 30 min over 35 sessions. Neuropsychological assessment and functional and structural MRI will be performed before and after 7 weeks training. Primary outcomes are global cognitive function and executive function. Secondary outcome measures are neuroplasticity changes measured by functional and structural MRI. Discussion Applying an internet-based, multi-domain, adaptive program, this study aims to assess whether cognitive training improves cognitive abilities and neural plasticity in patients with subcortical VCIND. In addition to the comprehensive assessment of the participants by neuropsychological tests, cerebrovascular risk factors and apolipoprotein E genotyping, neuroplasticity will be used as an evaluation outcome in this study for, to our knowledge, the first time. The combination of functional and structural MRI and neuropsychological tests will have strong sensitivity in evaluating the effects of cognitive training and will also reveal the underlying mechanisms at work. Trial registration ClinicalTrials.gov NCT02640716. Retrospectively registered on 21 December 2015.

The present study investigates whether the complement falsity elicited by strong non-factive verbs and the false belief activated by a standard nonverbal false belief task produce similar electrophysiological activities in the brain. The hypothesis is based on the notion that both complement falsity and false belief involve decoupling a false mental representation from reality. Some previous studies have reported a behavioral correlation between children's false belief reasoning and interpretation of strong non-factive verbs together with their false complements, but a neural basis for this correlation has not been found. Our event-related potential (ERP) results with normal adults showed that both nonverbal false belief and strong non-factive verb comprehension elicited a negative late slow waveform divergence compared to their respective baselines. Although these slow waves due to the two types of stimuli had slightly different scalp distributions, both were regarded as reflecting primarily frontal activation. Such ERP similarity provides evidence for a common neural basis shared by nonverbal false belief reasoning and comprehension of strong non-factive verbs.

Using event-related functional MRI, we examined the involvement of the left inferior frontal gyrus (LIFG) in explicit and implicit semantic processing of Chinese sentences. During scanning, Chinese readers read individually presented normal sentences with a contextually expected or unexpected target noun and were asked to perform an explicit or implicit semantic task (semantic or syntactic violation judgment). The conjunction analysis of the two tasks revealed LIFG as the critical brain region for semantic integration. Further, a cross-task comparison showed more extensive activations for the expectancy effect in the explicit task than in the implicit task in regions including bilateral anterior cingulate cortex/dorsolateral prefrontal cortex, left middle temporal gyrus, and right inferior frontal gyrus. These results indicate that LIFG is responsible for the integration process per se and that other brain regions observed in previous studies using explicit semantic tasks may be due to task-induced generic processes (e.g., cognitive control).

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.

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.

Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD = 2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms.

Age-related increases in right frontal cortex activation are a common finding in the neuroimaging literature. However, neurocognitive factors contributing to right frontal over-recruitment remain poorly understood. Here we investigated the influence of age-related reaction time (RT) slowing and white matter (WM) microstructure reductions as potential explanatory factors for age-related increases in right frontal activation during task switching. Groups of younger (N = 32) and older (N = 33) participants completed a task switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging (DTI) was performed. Two right frontal regions of interest (ROIs), the dorsolateral prefrontal cortex (DLPFC) and insula, were selected for further analyses from a common network of regions recruited by both age groups during task switching. Results demonstrated age-related activation increases in both ROIs. In addition, the older adult group showed longer RT and decreased fractional anisotropy in regions of the corpus callosum with direct connections to the fMRI ROIs. Subsequent mediation analyses indicated that age-related increases in right insula activation were mediated by RT slowing and age-related increases in right DLPFC activation were mediated by WM microstructure. Our results suggest that age-related RT slowing and WM microstructure declines contribute to age-related increases in right frontal activation during cognitive task performance.

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.

The Stroop task is a classic paradigm that can be used to examine cognitive control as it contains conditions with and without interference. Cumulative evidence suggests that both stimulus and response conflict contribute to the Stroop interference effect. However, it remains unclear whether there are dissociable event-related potential (ERP) or frequency band-specific electroencephalographic (EEG) power changes associated with stimulus conflict and response conflict. To investigate potential markers for each form of conflict, we applied a Stroop 2-1 mapping task in 20 healthy young adults. Results showed that a negative deflection in the 350-500ms time window (N450) and a positive deflection in the 600-900ms time window (late positive component, LPC) were associated with response conflict and stimulus conflict, respectively. Time-frequency analyses found that both stimulus and response conflict induced theta band power changes and that response conflict additionally induced a beta band power change. These results indicate that stimulus and response conflict in the Stroop task are associated with different ERP effects and brain oscillatory features.

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.