Investigating neural activity in response to core and non-core foods, as well as appetite and cardiometabolic biomarkers, may offer insight into why certain individuals are more vulnerable to develop food addiction (FA). This study aimed to investigate neural activation associated with FA during a food-related Go/No-Go functional magnetic resonance imaging (fMRI) task, as well as fasting blood biomarkers related to appetite regulation, stress, and cardiometabolic health. Adults aged 18-45, classified as FA (n=10) or non-FA (n=10) via the Yale Food Addiction Scale 2.0, completed a fasting blood sample and Go/No-Go task within the MRI scanner. Blood lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides], glycated haemoglobin (HbA1c) and glucose, and appetite-related hormones [oxytocin, ghrelin, leptin, cholecystokinin (CCK) and cortisol] were taken. Nineteen participants completed the scans (mean age 28.2±7.4y, 15 female). Individuals with FA showed greater activation in the right supramarginal gyrus, left angular gyrus and right middle frontal gyrus when withholding their button press for non-core food images (p<0.001, p=0.001, p=0.013 respectively). However, no significant differences between groups were identified for blood biomarkers of appetite, stress, or cardiometabolic health. Findings suggest that individuals with high YFAS scores required increased cognitive effort to suppress their responses towards non-core foods, which could increase their vulnerability to consumption of higher calorie foods. Future studies should investigate the role of inhibition and reward-related regions in individuals with FA through cumulative effects of visual, olfactory, and gustatory food cues to mimic the stimulation of all sensory components in the real-world food environment.

Working memory training (WMT) is widely used to enhance cognitive task performance, yet traditional delivery poses challenges for sustained implementation; computerised working memory training (CWMT) provides a scalable digital format with standardised delivery and integrated monitoring and feedback. We conducted the first meta-analysis integrating behavioural and neuroimaging evidence to quantify the behavioural effects and neural correlates of CWMT, drawing on 45 neuroimaging studies. Multivariate meta-analysis indicated a moderate benefit of CWMT relative to controls (Hedges' g = 0.503, 95% CI [0.363-0.642]). Seed-based d mapping (SDM) identified training-related decreases in activation in the left angular gyrus (L-AG), bilateral superior frontal gyrus (SFG), right inferior parietal lobule (R-IPL), left cerebellum, and right middle frontal gyrus (R-MFG), a pattern compatible with reduced recruitment following training. Moderator analyses showed significant effects of task type, training compliance, total training dose, and age, but not cognitive status and sex. Moreover, CWMT-induced brain activation changes were associated with behavioural improvements, and significant co-activation was observed among the brain regions identified in the overall analysis. Together, these findings provide convergent evidence that CWMT is associated with improved cognitive task performance and reproducible modulation of task-related activation, supporting its relevance as a scalable digital approach to cognitive health.

Neural correlates of happiness and its association with social avoidance and distress: Evidence from voxel-based morphometry and resting-state functional connectivity.

BACKGROUNDHepatic encephalopathy (HE) is the most common serious complication after transjugular intrahepatic portosystemic shunts (TIPS) surgery, the pathogenesis of which is not well understood.AIMTo explore the mechanisms of HE after TIPS from a cerebral hemodynamic perspective and provide a theoretical basis for clinical treatment, three-dimensional arterial spin labeling and resting-state functional magnetic resonance imaging were applied in patients with portal hypertension post-TIPS to analyze dynamic changes in cerebral blood flow (CBF) and spontaneous brain activity, respectively.METHODSPatients who meet the inclusion criteria were selected as the case group, and 18 healthy volunteers were assigned as the control group. The differences in amplitude of low-frequency fluctuation (ALFF) and CBF between the case group and the control group before TIPS surgery and the differences in ALFF and CBF between the case group at each detection time point were compared and analyzed, and analyze the correlation between the changes in ALFF and CBF in the case group and the changes in clinical data.RESULTSCompared with the healthy control group, the CBF values of patients with cirrhosis and portal hypertension who were treated with TIPS were reduced in the area centered on the right orbitofrontal gyrus and the left superior temporal gyrus. ALFF scores decreased in the area centered on the left superior temporal gyrus, the left inferior frontal gyrus of the operculum and the right precuneus. Compared with preoperatively, CBF in the TIPS group increased in the area centered on the left fusiform gyrus at 1 month after surgery and the difference in CBF in this area was negatively correlated with the difference in the Child-Pugh liver function score. ALFF values increased in the area centered on the left superior temporal gyrus and the ALFF difference in this area was positively correlated with the portal vein pressure difference. There was no significant difference in CBF 3 months after TIPS in comparison to pre-TIPS. ALFF scores increased in the area centered on the left orbitofrontal gyrus and the left precuneus 3 months after TIPS surgery and the difference in ALFF in the left orbitofrontal gyrus was negatively correlated with the difference in the Digit Symbol Substitution Test score. Compared to 1 month after TIPS surgery, CBF values decreased in the area centered on the right fusiform gyrus and increased in the area centered on the left angular gyrus 3 months after TIPS surgery. The difference in CBF in the right fusiform gyrus was positively correlated with the difference in the Number Connection Test Part A score. ALFF values decreased in the area centered on the right insula and in the cerebellum.CONCLUSIONTIPS surgery has a certain effect on spontaneous brain activity in patients with portal hypertension and cirrhosis for the increase in plasma ammonia as well as postoperative hemodynamic changes increasing CBF and may be factors causing HE. Resting-state functional magnetic resonance imaging is a sensitive diagnostic tool for HE, especially mild HE.

BACKGROUNDThe default mode network (DMN) is associated with lipid metabolism. Patients with major depressive disorder (MDD) exhibit concurrent abnormal topological properties of the DMN and dysregulated lipid metabolism. However, there are no studies investigating the mechanisms underlying the associations between these two variables in patients with MDD.AIMTo investigate the association between abnormal topological properties of the DMN and dysregulated lipid metabolism in patients with MDD.METHODSThere were 147 participants, including 71 patients with MDD and 76 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depression severity. Graph theoretical analysis was employed to compare group differences in the topological properties of the DMN across the following bilateral regions: the superior medial frontal gyrus, superior orbital frontal gyrus, posterior cingulate gyrus, parahippocampal gyrus, supramarginal gyrus (SMG), angular gyrus, precuneus, and middle temporal gyrus. Lipidomic techniques were employed to obtain lipid profiles, and orthogonal partial least squares discriminant analysis was performed to compare group differences in lipid profiles. Partial correlation analysis was performed between the abnormal topological properties of the DMN, HAMD-17 scores, and differential lipids.RESULTSAbnormal topological properties were observed in the MDD group in the following DMN regions: The right superior medial frontal gyrus (SFGmed.R), right posterior cingulate gyrus, left SMG, right SMG, and left angular gyrus. The betweenness centrality, degree centrality, and efficiency of the SFGmed.R were positively correlated with HAMD-17 scores, whereas the shortest path was negatively correlated with HAMD-17 scores. The betweenness centrality of the left SMG was positively correlated with HAMD-17 scores. The betweenness centrality of the SFGmed.R was positively correlated with phosphatidylcholine O-34:3 and triglyceride O-8:0_18:3_18:5 levels.CONCLUSIONSFGmed.R is a crucial node within the DMN in MDD patients, and the betweenness centrality of the SFGmed.R is associated with phosphatidylcholine and triglyceride levels. These results may offer novel clues for exploring the pathophysiology and biomarker identification of MDD.

Introduction: Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive intervention that could effectively enhance the cognitive function in patients with amnestic mild cognitive impairment (aMCI). However, the mechanism and predictive biomarkers for therapeutic response remain poorly understood. Methods: Fifty-three aMCI patients underwent either neuro-navigated rTMS (n=28) or sham stimulation (n=25) targeting the left angular gyrus over four weeks (registered in 2021: ChiCTR2100050496). Multimodal MRI and comprehensive neuropsychological assessments were conducted pre- and post-intervention. Changes in brain communication networks and their correlation with cognitive improvements were analysed, with random forest models applied to predict treatment efficacy. Results: Episodic memory (p&lt; 0.001) and general cognitive function (p&lt; 0.05) of aMCI patients were significantly improved after intervention. Novel alterations in brain communications networks were identified in 5 sensorimotor areas, executive control regions, and emotion-cognition processing hubs. Communication alterations between the right precentral gyrus and right angular gyrus were positively correlated with the improvements in episodic memory (r=0.38, p=0.046), while the alterations between right precentral gyrus and right angular gyrus were negatively correlated with improvements in general cognitive function (MMSE, r=-0.44, p=0.019; MoCA, r=-0.43, p=0.024). Notably, the random forest model integrating communication network patterns with baseline demographic and neuropsychological data showed strong power in predicting rTMS effects. Discussion: These findings advance understanding of rTMS mechanisms by linking network plasticity to cognitive gains, addressing critical knowledge gaps. Conclusion: Neuro-navigated rTMS targeting the left angular gyrus may enhance cognitive function in aMCI patients by improving inter-brain regions communication. Baseline communication patterns hold promise as predictive biomarkers, facilitating personalized treatment strategies.

Humans can create completely new concepts through semantic composition. These "conceptual combinations" can be created by attributing the features of one concept to another (e.g., a "lemon flamingo" might be a yellow flamingo) or drawing on a relationship between concepts (e.g., a "lemon flamingo" might consume lemons). We ask how semantic composition modulates the neural representations of underlying concepts. Combining fMRI with multivariate pattern analysis, we interrogate neural patterns for concepts before and after they were subjected to semantic composition. We observe a postcomposition shift in neural patterns underlying weakly constrained concepts in the visual system. The composition of strongly constrained combinations draws on a network of semantic regions that include the right inferior frontal gyrus, left angular gyrus, left lateral anterior temporal lobe, and posterior cingulate cortex. Finally, a subset of the semantic network, in the left parahippocampal gyrus, distinguishes the manner of composition: relational or attributive. These findings reveal that semantic composition has neural consequences for the composed concepts and that the manner of composition affects how the brain's semantic network is deployed.

Abstract Classroom-based language learning has typically taken place in relatively static body positions, but research suggests that embodied learning through sensorimotor engagement and technical immersion, using virtual realities, can significantly enhance learning outcomes. Recent research has linked differences in the learning context to different cortical structures within the language learning network. In this study, we investigated the effect of technical immersion and sensorimotor engagement on performance in behaviour and grey matter volume in the brain after a single 20-minute language learning task. We tested two learning environments: a low-embodied desktop-based virtual (dVE) environment using a computer screen and a high-embodied virtual reality (iVR) environment using a head-mounted display, as well as a no training group. We assessed morphological brain changes using Magnetic Resonance Imaging (MRI) at 7 Tesla before and after training. Participants with less sensorimotor engagement, compared to those with high, performed significantly better and showed higher grey matter volume in the left angular gyrus, a key hub region for vocabulary training within the language network, as well as in the left middle temporal gyrus, a region associated with lexical semantic processing. However, we could not identify a difference between the dVE and iVR groups. Our results suggest that both virtual platforms, although different in the level of immersion and whole-body involvement, rely on similar cortical structures within the language learning network. Further, sensorimotor engagement might have a stronger influence on performance and related brain changes than the learning context itself.

BackgroundCognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), yet its underlying mechanisms remain poorly understood. Apolipoprotein E4 (APOE4), a genetic risk factor of Alzheimer’s Disease, has been associated with PD-related cognitive impairment. However, findings are inconsistent, highlighting the need for further investigation. Neuroimaging studies have found gray matter abnormalities, mainly reductions in gray matter volume (GMV) and cortical thickness (CTh), in both cognitively impaired PD patients and APOE4 carriers. Yet, APOE4’s role in these structural changes and their cognitive impact in PD is underexplored.AimThis study aimed to determine whether APOE4 influences early structural brain differences in terms of GMV and CTh in PD prior to the emergence of cognitive dysfunction.MethodsA total of 51 PD APOE4 carriers and 120 non-carriers who were cognitively unimpaired from the Parkinson’s Progression Markers Initiative (PPMI) database were included. T1-weighted MRI scans were used to calculate GMV and CTh in regions previously associated with PD-related cognitive impairment, including hippocampal subregions. Cognitive scores assessing global cognition and specific cognitive domains were used to examine associations between regions showing significant GMV or CTh group differences and cognitive performance.ResultsPD APOE4 carriers showed increased GMV in the left angular gyrus (AnG) and decreased GMV in the left nucleus accumbens (NAcc) compared to non-carriers, though neither survived multiple comparison correction. Left AnG GMV correlated with visuospatial function in both groups but did not remain significant after co-variate adjustment. Left NAcc GMV correlated with visuospatial function and working memory, but only in non-carriers even after co-variate adjustment. No group differences were observed in CTh measures and hippocampal subregion GMVs.ConclusionsThis study suggests that APOE4 may not influence cognitive function in PD by affecting GMV and CTh. However, longitudinal analyses must confirm these observations.

Brain Mapping for Surgical Resection of Left Dominant Supramarginal and Angular Gyrus Grade II Ependymoma: 2-Dimensional Operative Video.

IntroductionOlfactory dysfunction is common in the Alzheimer’s Disease continuum, and olfaction may be altered before clinical syndrome onset. The present study aimed at investigating the functional connectivity of the olfactory cortex and its correlation with olfaction performance in a group of patients with Mild Cognitive Impairment (MCI) who subsequently converted or not converted to Alzheimer’s Disease (AD) dementia.MethodsAt baseline, 30 MCI patients were evaluated with the Sniffin’ Sticks (threshold, discrimination, and identification) to assess olfactory capacities, and they were followed up over time to identify converter and stable patients. Resting-state fMRI data acquired at baseline were analyzed to assess functional connectivity of left and right olfactory cortex. Beta values were extracted from the stable versus converter contrasts and correlated with olfactory scores.ResultsFunctional connectivity of the olfactory cortex was significantly increased with the posterior cingulate cortex, and significantly decreased with middle cingulate cortex, supplementary motor area, and left pre- and postcentral gyri, in converter compared to stable patients. Reduced negative functional connectivity between olfactory cortex and left angular gyrus emerged in converter patients, and a negative correlation was found between angular gyrus and discrimination scores.DiscussionOur findings indicate alterations of functional connectivity of the olfactory cortex in subjects with MCI at risk of conversion to AD dementia, even at the early stages of the disease. Additionally, the negative correlation between olfactory ability and the angular gyrus functional connectivity, a cerebral region known to be involved in multisensory integration processing, may be considered as a marker of disease progression.

Hypergraph-Based Multimodal MRI Reveals Thalamus-Mediated Network Dyscoordination Underlying Motor Impairments in Parkinson's Disease.

ABSTRACT Introduction Metacognition can be negatively affected after moderate to severe traumatic brain injury (TBI). This study utilized functional magnetic resonance imaging (fMRI) to identify patterns of neural activation associated with metacognitive confidence judgments after moderate to severe TBI. Method Twenty-four adults with chronic moderate to severe TBI and 10 non-injured adults (nonTBIs) were scanned while performing a meta-memory recognition task. Metacognitive accuracy was quantified using a signal detection theory approach. Activation present during the metamemory task, as well as group differences in activation correlated to metacognitive accuracy were identified. Results Adults with TBI did not differ in their metacognitive accuracy from nonTBIs; however, differences in neural recruitment were noted. Adults with TBI demonstrated stronger relationships between metacognitive performance and activation in the left angular gyrus and left supramarginal gyrus, while nonTBIs showed stronger associations in the left superior parietal lobule, left lateral occipital cortex, left precuneus, and left occipital fusiform gyrus. Conclusions The findings suggest that different neural resources may be used after TBI to facilitate metacognitive processing and to modulate the direction of confidence accuracy. Particularly, greater activation in the angular gyrus may reflect strategies to rely on monitoring processes and enhanced memory to facilitate metacognitive processing post-injury.

Comparing information structures in between deep neural networks (DNNs) and the human brain has become a key method for exploring their similarities and differences. Recent research has shown better alignment of vision-language DNN models, such as contrastive language-image pretraining (CLIP), with the activity of the human ventral occipitotemporal cortex (VOTC) than earlier vision models, supporting the idea that language modulates human visual perception. However, interpreting the results from such comparisons is inherently limited owing to the 'black box' nature of DNNs. Here we combine model-brain fitness analyses with human brain lesion data to examine how disrupting the communication pathway between the visual and language systems causally affects the ability of vision-language DNNs to explain the activity of the VOTC to address this. Across four diverse datasets, CLIP consistently captured unique variance in VOTC neural representations, relative to both label-supervised (ResNet) and unsupervised (MoCo) models. This advantage tended to be left-lateralized at the group level, aligning with the human language network. Analyses of 33 patients who experienced a stroke revealed that reduced white matter integrity between the VOTC and the language region in the left angular gyrus was correlated with decreased CLIP-brain correspondence and increased MoCo-brain correspondence, indicating a dynamic influence of language processing on the activity of the VOTC. These findings support the integration of language modulation in neurocognitive models of human vision, reinforcing concepts from vision-language DNN models. The sensitivity of model-brain similarity to specific brain lesions demonstrates that leveraging the manipulation of the human brain is a promising framework for evaluating and developing brain-like computer models.

ABSTRACT Creative problem-solving relies on the flexible reorganization of prior knowledge to reshape complex memory structures, yet the behavioral and neural processes supporting this transformation remain poorly understood. The angular gyrus (AG) may play a key role in creativity-driven restructuring by integrating semantic information. To investigate this, participants underwent anodal transcranial direct current stimulation (tDCS) over the left AG or sham stimulation during a creative story generation task. Pre- and post-task semantic memory structures were assessed via free association and relatedness judgment tasks under electroencephalography (EEG). We found that creative ideation facilitated semantic memory restructuring – measured with increased network connectivity and decreased network compartmentalization, indicating a more integrated and flexible network, typically under anodal tDCS. At the neural level, creative ideation was associated with reduced N400 (lower semantic integration effort) and decreased neural representation similarity (greater flexibility) for unrelated story words, primarily observed in frontal regions under anodal tDCS. Moreover, these restructuring effects were specifically predicted by creative ideation and anodal tDCS. Critically, creative ideation functions not as a mediator of tDCS effects, but as a direct driver of restructuring. These findings highlight the unique role of creativity, particularly with anodal stimulation of the left AG, in driving knowledge restructuring.

Migraine without aura (MWoA) is linked to abnormal subcortical/cortical network activity and neurotransmitter dysregulation. However, the alteration of functional integration and the information flow between brain networks participated in pain sensory pathway and the patterns of neurotransmitter dysregulation during the interictal period remain unclear. This cross-sectional study compared 53 interictal MWoA patients and 51 healthy controls using resting-state fMRI. Whole-brain functional integration (degree centrality, DC) and effective connectivity (EC) were analyzed. JuSpace toolbox mapped spatial correlation between functional alterations and neurotransmitter systems. MWoA patients showed decreased DC in the left putamen and increased DC in the left angular gyrus. Altered EC from subcortical to cortical regions included pathways from the left putamen to right medial superior frontal gyrus, supramarginal gyrus, dorsolateral superior frontal gyrus, and postcentral gyrus, as well as bilateral caudate to left angular gyrus. Cortical-to-subcortical EC changes involved right dorsolateral superior frontal gyrus to left putamen and left angular gyrus to left caudate. EC from left putamen to right postcentral gyrus inversely correlated with headache frequency, while right caudate to left angular gyrus EC positively correlated with disease duration. Altered DC patterns spatially overlapped with serotonergic, dopaminergic, and glutamate pathways and correlated with quality-of-life impairments (MSQ scores). MWoA involves disrupted functional integration and bidirectional subcortical-cortical connectivity during interictal periods, associated with headache severity and neurotransmitter system imbalances. These findings highlight network-level pathophysiology and neurochemical dysregulation underlying migraine.

Stroke location is an important determinant of post-stroke cognitive impairment (PSCI). In young adults, a comprehensive map of lesion patterns and their relations to PSCI is lacking. This study aims to identify lesion locations associated with poorer cognitive performance in patients with stroke at a young age. We conducted a multicenter prospective cohort study between 2013 and 2021, enrolling patients aged 18-49years with first-ever ischemic stroke and a visible stroke lesion on MRI. Cognitive assessments were performed within six months post-stroke, covering seven domains. We categorized patients as having no/mild or major vascular cognitive disorder (VCD), defined as a Z-score<-2.0 in one or more domains. We assessed aphasia by the NIHSS language subscale. We performed multivariate lesion-symptom mapping to identify lesion locations associated with major VCD, poorer cognitive performance in each domain, and aphasia. Among 522 patients (median age 44.3years [IQR 37.7-41.5]; 257 [49.2%] women), 168 (32.2%) had major VCD. Lesions in both hemispheres and cerebellar regions were associated with presence of a major VCD, and lower performance in episodic memory, processing speed, executive functioning, language, and attention and working memory. Aphasia had the strongest relationship with left fronto-temporo-parietal regions, while the left angular gyrus was the region most associated with major VCD. We show that lesion locations associated with poorer cognitive performance in young stroke patients are widely distributed, including cerebellar regions. This study showcases the complexity in the relationships between affected brain regions and cognitive symptoms, explaining the variability in post-stroke cognitive outcome.

Abstract Major depressive disorder in the context of dementia (MDD + D) is highly prevalent, on the rise, and a leading cause of impairment in older adults. It accelerates functional decline, worsens health outcomes, hastens long-term care admission, increases caregiver burden, and raises mortality risk. MDD+D involves brain network dysfunction affecting mood and memory. Transcranial direct current stimulation (tDCS) improves mood in MDD, while transcranial alternating current stimulation (tACS) enhances memory in dementia. Combining these neuromodulation techniques offers a promising dual-targeted intervention. This study evaluates the safety and feasibility of a home-based, caregiver-administered tACS + tDCS intervention. Ten participants (8 female, average age 73 ± 7.13) underwent a 4-week intervention consisting of 20-minute sessions, five days per week, targeting the left prefrontal cortex (tDCS) and left angular gyrus (tACS). Caregivers, trained by study staff, administered the stimulation with initial tele-supervision before continuing independently with remote monitoring. Participants completed questionnaires to assess safety and feasibility. Following the intervention, participants assessed their experience. All ten participants completed the study, with eight adhering to 100% of sessions, one completing 95%, and one 90%. Across 197 total sessions, the most reported side effect was scalp sensations (tingling, itching), mild in 55%, moderate in 21%, and severe in 1%. 90% of participants expressed willingness to repeat the program and continue for a longer duration. A home-based tACS + tDCS program is feasible, safe, and well-tolerated, with high adherence and satisfaction, supporting further investigation into at-home tACS + tDCS treatment for MDD+D.

BackgroundHemiplegic shoulder pain (HSP), a common complication of stroke, has a reported incidence of 34%–85% and a complex pathophysiology. This study aimed to explore differences in brain network topological properties between patients with and without HSP after stroke using resting-state functional magnetic resonance imaging.MethodFifty patients with hemiplegia after stroke were recruited and divided into two groups based on the presence of HSP. Resting-state functional magnetic resonance imaging data were acquired, and GRETNA was applied to calculate both global and regional network topological properties. Group differences were assessed between patients with and without HSP.ResultsAt the global network level, both groups demonstrated a clear small-world organization (small-worldness index > 1). Compared with the non-pain group, patients with HSP showed significantly lower global efficiency (0.1733 ± 0.0047 vs. 0.1765 ± 0.0044; P = 0.02) and higher characteristic path length (0.3224 ± 0.0152 vs. 0.3170 ± 0.0089; P = 0.001). At the regional network level, patients with HSP showed reduced nodal degree centrality and nodal local efficiency in the opercular part of the right inferior frontal gyrus and in the orbital gyrus (P < 0.05). They also exhibited decreased nodal betweenness centrality in the right pallidum, left dorsolateral superior frontal gyrus, triangular part of the left inferior gyrus, and left Rolandic operculum (P < 0.05). Conversely, nodal betweenness centrality was increased in the left thalamus, right parahippocampal gyrus, left inferior occipital gyrus, and left angular gyrus (P < 0.05).ConclusionsThe topological properties of brain networks in patients with HSP have shifted toward a weaker small-world organization. Nodal alterations were primarily concentrated in the executive control network, default mode network, basal ganglia, and language network, regions associated with pain processing and emotional regulation. These findings provide new insights into the central mechanisms of HSP after stroke and suggest potential neural targets for future research and therapeutic intervention.

This study investigates intelligence-related differences in the adjustment of brain activity and connectivity to varying cognitive demands, testing for a moderation of an association between intelligence and neural efficiency by task difficulty. In 72 young adults (34 female, 38 male), fMRI brain activity changes during a decision-making task with five levels of difficulty were related to intelligence scores from a nonverbal matrix reasoning test. In frontoparietal, subcortical, and cerebellar regions activated during task processing, we observed smaller increases in brain activity in more intelligent participants-independent of task difficulty. However, in two regions of the default mode network, dorsomedial prefrontal cortex and left angular gyrus, more intelligent participants showed greater decreases in activity with increasing task difficulty. Furthermore, with increasing difficulty, more intelligent participants showed greater increases in functional connectivity of dorsomedial prefrontal cortex and angular gyrus. These findings suggest a more dynamic adjustment of neural processing to varying cognitive demands in more intelligent individuals. Particularly when it comes to more difficult tasks, more intelligent people seem to be better able to down-regulate activity in the brain's default mode network. Due to the relatively small sample size, these findings must be considered preliminary. While their interpretation should therefore be treated with caution, they suggest conceptually new avenues for replication in larger samples. As far as the observed processes reflect the suppression of task-unrelated neural processing and a better focus on the task at hand, they can potentially explain the general performance advantage of more intelligent individuals across various cognitive tasks.