Understanding the role of the frontal lobe in tool-use tasks: how much does it represent domain-general rather than domain-specific contribution?

Specific and general relationships between cortical thickness and cognition in older adults: a longitudinal study

IntroductionCognitive impairment has been identified in patients with non-central nervous system cancer received chemotherapy. Chemotherapy-induced changes in the brain are considered as the possible causes of the cognitive deficits of patients. This study aimed to explore chemotherapy-related functional brain changes and cognitive impairment in rectal cancer (RC) patients who had just finished chemotherapy treatment.MethodsIn this study, RC patients after chemotherapy (on the day patients received the last dose of chemotherapy) (n=30) and matched healthy controls (HCs) (n=30) underwent cognitive assessments, structural magnetic resonance imaging (MRI) and resting-state functional MRI. The functional brain networks were constructed by thresholding the partial correlation matrices of 90 brain regions in the Anatomical Automatic Labeling template and the topologic properties were evaluated by graph theory analysis. Moreover, correlations between altered topological measures and scores of cognitive scales were explored in the patient group.ResultsCompared with HCs, RC patients had lower scores of cognitive scales. The functional brain network had preserved small-world topological features but with a tendency towards higher path length in the whole network. In addition, patients had decreased nodal global efficiency (Eglo(i)) in the left superior frontal gyrus (dorsolateral), superior frontal gyrus (orbital part), inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part) and right inferior frontal gyrus (triangular part). Moreover, values of Eglo(i) in the superior and inferior frontal gyrus were positively associated with cognitive function in the patient group.ConclusionThese results suggested that cognitive impairment was associated with disruptions of the topological organization in functional brain networks of RC patients who had just finished chemotherapy, which provided new insights into the pathophysiology underlying acute effects of chemotherapy on cognitive function.

38. The effect of repetitive transcranial magnetic stimulation on attention and psychomotor speed in patients with mild cognitive impairment and early Alzheimer’s disease

Post-chemotherapy cognitive impairment, also known as 'chemobrain', is a common neurotoxic complication induced by chemotherapy, which has been reported in many cancer survivors who have undergone chemotherapy. In this study, we aimed to explore the effects of D-neneneba dicitabine, C-nenenebb cytarabine, A-aclamycin, G-granulocyte colony-stimulating factor (D-CAG) chemotherapy on cognitive function in patients with acute myeloid leukaemia (AML) and its possible central mechanisms. Twenty patients with AML and 25 matched healthy controls (HC) were enrolled in this study. The cognitive function of patients before and after D-CAG chemotherapy was evaluated by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). The resting-state functional magnetic resonance imaging data were collected from all patients before and after chemotherapy intervention, as well as HC. Then, resting-state functional magnetic resonance imaging data were preprocessed using DPABI software package and regional homogeneity (ReHo) values of brain regions were calculated. Finally, ReHo values between groups were compared by Resting-State fMRI Data Analysis software package with t-tests and Alphasim method was performed for multiple comparison correction. Moreover, associations between ReHo values of altered brain regions and the scores of FACT-Cog were analysed by Pearson correlation. The total FACT-Cog scores and four factor scores of AML patients increased significantly after treatment. ReHo values showed no significant changes in patients before treatment when compared with HC. Compared with HC, ReHo values of the right middle frontal gyrus, inferior frontal gyrus (opercular part), middle occipital gyrus, and left praecuneus decreased significantly, while ReHo values of the left inferior temporal gyrus, right middle temporal gyrus, and hippocampus increased significantly in patients after treatment. Compared with patients before treatment, ReHo values decreased significantly in the right middle frontal gyrus, inferior frontal gyrus (opercular part), and middle and inferior occipital gyri of patients after treatment. In addition, ReHo values of the right inferior frontal gyrus (opercular part) were negatively correlated with the total scores of FACT-Cog and factor scores of perceived cognitive impairment in patients after treatment. There were also negative correlations between ReHo values of the right middle frontal gyrus and perceived cognitive impairment scores. The present study confirmed that D-CAG chemotherapy might cause impaired subjective self-reported cognitive functioning in AML patients, which might be related to the decreased function of certain regions in the right prefrontal lobe. These findings provided further understanding of the mechanisms involved in post-chemotherapy cognitive impairment and would help develop new therapeutic strategies for 'chemobrain' in AML patients.

To investigate differences in the age-related decline in brain tissue concentration between Masters athletes and sedentary older adults. Twelve Masters athletes (MA) (three females, age = 72.4 ± 5.6 years, endurance training >15 years), 12 sedentary elderly (SE) similar in age and educational level (four females, age = 74.6 ± 4.3 years), and nine young controls (YC) (four females, age = 27.2 ± 3.6 years) participated. T1-weighted high-resolution (1 × 1 × 1mm(3) ) images were acquired. Voxel-based analysis was conducted to identify clusters showing tissue concentration differences with t-tests. Cognitive function was assessed using a standard clinical battery focused on executive function and memory. Two MA and two SE were unable to complete the magnetic resonance imaging (MRI) study. Both SE and MA showed lower gray matter (GM) concentrations than YC in the superior, inferior and middle frontal gyrus, superior temporal gyrus, postcentral gyrus, and the cingulate gyrus (PFDR-corrected < 0.001) and lower white matter (WM) concentrations in the inferior frontal gyrus and precentral gyrus (PFDR-corrected < 0.005). Notably, MA showed higher GM and WM concentrations than SE in the subgyral, cuneus, and precuneus regions related to visuospatial function, motor control, and working memory (PFDR-corrected < 0.005). After controlling for estimated intelligence, MA outperformed SE on tasks of letter (P < 0.01) and category (P < 0.05) fluency. Life-long exercise may confer benefits to some aspects of executive function and age-related brain tissue loss in the regions related to visuospatial function, motor control, and working memory in older adults.

Nonalcoholic fatty liver disease (NAFLD) has been proven to be associated with an increased risk of cognitive impairment and dementia, and this association is more significant in non-obese NAFLD populations, but its pathogenesis remains unclear. Our study aimed to explore the abnormalities of spontaneous brain activity in non-obese NAFLD patients by resting-state fMRI (RS-fMRI) and their relationship with cognitive function. 19 non-obese NAFLD, 25 obese NAFLD patients, and 20 healthy controls (HC) were enrolled. All subjects underwent RS-fMRI scan, psychological scale assessment, and biochemical examination. After RS-fMRI data were preprocessed, differences in low-frequency fluctuation amplitude (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared among the three groups. Furthermore, the relationship between RS-fMRI indicators and cognitive and clinical indicators were performed using correlation analysis. The cognitive function was declined in both NAFLD groups. Compared with obese NAFLD patients, non-obese NAFLD patients showed increased ALFF and ReHo in the left middle temporal gyrus (MTG), increased ReHo in the sensorimotor cortex and reduced FC between left MTG and right inferior frontal gyrus (IFG). Compared with HC, non-obese NAFLD patients showed increased ALFF and ReHo in the left calcarine cortex and fusiform gyrus (FG), decreased ALFF in the bilateral cerebellum, and reduced FC between left FG and right IFG and left angular gyrus. In addition to the same results, obese patients showed increased activity in different regions of the bilateral cerebellum, while decreased ALFF in the right superior frontal gyrus and ReHo in the right orbitofrontal cortex (OFC). Correlation analysis showed that in non-obese patients, the ALFF values in the FG and the FC values between the left MTG and the right IFG were associated with cognitive decline, insulin resistance, and fasting glucose disorder. Non-obese NAFLD patients showed abnormal local spontaneous activity and FC in regions involved in the sensorimotor, temporo-occipital cortex, cerebellum, and reward system (such as OFC), some of which may be the potential neural mechanism difference from obese NAFLD patients. In addition, the temporo-occipital cortex may be a vulnerable target for cognitive decline in non-obese NAFLD patients.

Inferior frontal gyrus seed-based resting-state functional connectivity and sustained attention across manic/hypomanic, euthymic and depressive phases of bipolar disorder

Our main goal was to determine the influence of white matter integrity on the dynamic coupling between brain regions and the individual variability of cognitive performance in older adults. Electroencephalography was recorded while participants performed a task specifically designed to engage working memory and inhibitory processes, and the associations among functional activity, structural integrity, and cognitive performance were assessed. We found that the association between white matter microstructural integrity and cognitive functioning with aging is mediated by time-varying alpha and gamma phase-locking value. Specifically, better preservation of the inferior fronto-occipital fasciculus in older individuals drives faster task-related modulations of alpha and gamma long-range phase-locking value between the inferior frontal gyrus and occipital lobe and lower local phase-amplitude coupling in occipital lobes, which in turn drives better cognitive control performance. Our results help delineate the role of individual variability of white matter microstructure in dynamic synchrony and cognitive performance during normal aging.

The neurobiological mechanism of borderline personality disorder (BPD) in adolescents remains unclear. The study aimed to assess the alterations in neural activity within prefrontal cortex in adolescents with BPD and investigate the relationship of prefrontal activity with emotional regulation and cognitive function. This study enrolled 50 adolescents aged 12-17 years with BPD and 21 gender and age-matched healthy control (HC) participants. Study assessment for each participant included a brain resting-state functional MRI (rs-fMRI), clinical assessment questionnaires such as Borderline Personality Features Scale (BPFS), Difficulties in Emotion Regulation Scale (DERS), Ottawa Self-Injury Inventory and Childhood Trauma Questionnaire (CTQ) and cognitive testing with Stroop Color-Word Test (SCWT). Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based functional connectivity (FC) were obtained from rs-fMRI analysis. Correlation analysis was also performed to evaluate the associations of the neuroimaging metrics such as fALFF and FC with clinical assessment questionnaire and cognitive testing scores. Adolescents with BPD showed increased fALFF values in the right inferior frontal gyrus and decreased activity in the left middle frontal gyrus as compared to the HC group (p < 0.05, cluster size ≥ 100, FWE correction). In adolescents with BPD, increased fALFF in the right inferior frontal gyrus was related to the BPFS (emotional dysregulation), DERS-F (lacking of emotional regulation strategies) and Ottawa Self-Injury Inventory-4C scores (internal emotional regulation function of self-injurious behavior). The reduced fALFF in the left middle frontal gyrus was associated with the SCWT-A (reading characters) and the SCWT-B (reading color) scores. Additionally, the fALFF values in the left middle frontal gyrus and the right inferior frontal gyrus were related to the CTQ-D (emotional neglect) (p < 0.05). The left middle frontal gyrus exhibited increased FC with the right hippocampus, left inferior temporal gyrus and right inferior frontal gyrus (voxel p < 0.001, cluster p < 0.05, FWE correction). The increased FC between the left middle frontal gyrus and the right hippocampus was related to the SCWT-C (cognitive flexibility) score. We observed diverging changes in intrinsic brain activity in prefrontal cortex, and neural compensatory changes to maintain function in adolescents with BPD. In addition, decreased neural function was closely associated with emotional dysregulation, while increased neural function as indicated by brain activity and FC was associated with cognitive dysfunction. These results indicated that alterations of intrinsic brain activity may be one of the underlying neurobiological markers for clinical symptoms in adolescents with BPD.

Objective To explore the effect of single nucleotide polymorphisms in CSMD1 on grey matter volume (GMV) and verbal fluency in schizophrenic patients. Methods Eighty-seven schizophrenic patients and 98 normal controls underwent MRI scanning, cognitive assessment and whole-genome genotyping. Linear regression model was conducted to explore the association between the genotype of CSMD1 and cognitive function (digit symbol substitution test (DSST) ,verbal fluency test (VFT) ) ; The full factorial analysis was conducted to explore the effect of CSMD1 gene and diagnosis and diagnosis×gene interaction on GMV, then did the post hoc analysis and explored the association between cognition and the GMV of diagnosis×gene interaction. Results The performance scores of DSST (t=-7.51, P 10); the post hoc analysis showed that compared with the CSMD1 rs17405197 AC+CC carriers, the GMV in the above regions significantly decreased in subjects with AA genotype. The interaction effect between the diagnosis and genotype was found in the pars opercularis of right inferior frontal gyrus (MNI (x, y, z) : 51, 20, 15, F=20.55, P 100). The partial correlation analysis showed that only in the patient group, the GMV in the pars opercularis of right inferior frontal gyrus was negatively correlated with VFT score (r=-0.28, P=0.01) . Conclusion The effect of GSMD1 rs17405197 polymorphism on the pars opercularis of right inferior frontal gyrus in patients with schizophrenia might underly the neuropathological bases of their VFT impairment. Key words: Schizophrenia; Polymorphism, single nucleotide; Cognition; CUB and Sushi multiple domains1; Grey matter volume

Language production in bilinguals relies on the collaborative interaction between two neural systems: the language control system (e.g. the right inferior frontal gyrus) and the language processing system (e.g. the left superior temporal gyrus). However, the causal mapping between these brain systems and their cognitive functions, as well as the temporal dynamics between these two systems during bilingual language production, remain unclear. To investigate this, our study applied online transcranial magnetic stimulation to the right inferior frontal gyrus and left superior temporal gyrus in Chinese-English bilinguals performing a language-switching task. Transcranial magnetic stimulation was administered within seven 100 ms time windows (TW1 to TW7) following the picture onset. We observed time window-specific enhancements of language control, as shown by a significant reduction in switching costs upon the stimulations on both sites relative to the sham stimulation: specifically, the right inferior frontal gyrus at TW1, TW2, TW4, and TW5 and the left superior temporal gyrus at TW2 and TW5. These findings indicate a double-strike top-down control mechanism underpinned by the pathway from the right inferior frontal gyrus to the right inferior frontal gyrus, potentially during both stages during production: the language task schema and the lemma selection. Our study provides the first evidence of the dynamic interactions between language control and processing systems causally underpinning bilingual language production.

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW > UTW) and condition (task > resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate corrected p-value, p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.

Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Introduction: The combination of verbal and non-verbal cognitive dysfunction in post-stroke aphasia (PSA) patients may ultimately affect social interactions. However, the underlying neural mechanisms of both verbal and non-verbal cognitive impairment remain unclear. This study aimed to investigate the activity and functional abnormalities of local and remote brain regions and their relationship with cognitive behaviour, to provide more effective guidance in future clinical therapy. Methods: We recruited 46 PSA patients and 40 normal controls(NCs) matched for general characteristics in this study and evaluated their verbal and non-verbal cognitive functions. Functional magnetic resonance imaging(fMRI) was used to examine the fractional amplitude of low-frequency fluctuations(fALFF), regional homogeneity(ReHo), and functional connectivity(FC) in PSA patients. Independent two-sample t-tests were used to identify differences in these measures between two groups. Moreover, partial correlation analyses were performed to determine the correlation between FC from the affected brain regions and language and cognitive performance in PSA patients. Results: This study revealed that PSA patients presented significantly lower fALFF and ReHo values in right cerebellum superior (CRBL.Superior.R), left thalamus(THA.L), and left middle frontal gyrus(MFG.L). Moreover, the FC in the MFG.L-left inferior frontal gyrus, orbital part was significantly lower among PSA patients and was positively correlated with language and cognitive performance(p&lt; 0.05). The CRBL. Superior. R-left caudate nucleus and right lenticular nucleus FC were also decreased and were associated with cognitive function(p&lt; 0.05). In addition, PSA patients were further divided into fluent and nonfluent groups. The results revealed that nonfluent patients performed worse in verbal and non-verbal cognitive performance(p&lt; 0.05) and had weaker performance in the THA.L and left supplementary motor area FC(p&lt; 0.001). Conclusions: This study provides new evidence that abnormal neural activity and functional connectivity within specific brain regions may play crucial roles in language and cognitive processing. The underlying mechanisms of impaired linguistic function accompanied by decline in cognition may be a partial overlap between language and cognitive-related brain networks. In future, combining cognitive and linguistic functions and designing a comprehensive treatment plan will be the focus of rehabilitation.

Vascular Cognitive Impairment (VCI) is a common type of dementia that affects the quality of life and lacks effective treatments. The Dengzhan Shengmian capsule (DZSM), a traditional Chinese medicine, is clinically used to alleviate VCI symptoms, but its therapeutic mechanisms are not fully understood. This study aimed to evaluate the neuroprotective effects of DZSM in VCI patients by investigating its impact on cognitive function and brain structure, thereby providing neuroimaging evidence for its clinical application. A randomized, double-masked, 6-month trial was conducted with 100 VCI patients, assigned to either the experimental group receiving DZSM (n = 50) or the placebo group (n = 50). The efficacy of DZSM in VCI patients was assessed through cognitive behavioral assessments and neuroimaging data collected at baseline and after 6 months. A comparison was made across groups to determine cognitive and neural changes associated with the intervention. Participants receiving DZSM exhibited significant improvements across multiple cognitive domains compared to the placebo, including global cognition (MMSE, p = 0.019; ADASCog, p < 0.001), episodic memory (AVLT-N1N5, p < 0.001), visuospatial ability (CDT, p = 0.034), and working memory (DST, p = 0.015). For brain structure, the gray matter volume in the right postcentral and precentral gyrus, bilateral cuneus, left supplementary motor area, superior occipital gyrus, right hippocampus, right thalamus, bilateral lingual gyrus, left precuneus, right inferior frontal gyrus (triangular part), left inferior parietal gyrus, left superior medial frontal gyrus, right superior temporal gyrus, left middle temporal gyrus, and right parahippocampal gyrus increased in the DZSM group (FDR-corrected, p<0.05), with no significant changes in white matter microstructure. Moreover, gray matter volume increases positively correlated with improvements in global cognition and visuospatial function. DZSM capsules significantly improved multiple cognitive domains in VCI patients, particularly memory, visuospatial, and executive functions. The observed increases in gray matter volume suggest that DZSM may exert neuroprotective effects through structural brain remodeling, which is closely associated with cognitive enhancement. This study identifies brain structural abnormalities in VCI patients that correlate with cognitive deficits. DZSM capsule treatment significantly improved cognitive function. While the underlying mechanisms remain to be fully elucidated, these effects may be related to structural changes in the brain.