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Introduction Resting‐state functional magnetic resonance imaging (fMRI) is widely used for measuring functional interactions between brain regions, significantly contributing to our understanding of large‐scale brain networks and brain–behavior relationships. Furthermore, idiosyncratic patterns of resting‐state connections can be leveraged to identify individuals and predict individual differences in clinical symptoms, cognitive abilities, and other individual factors. Idiosyncratic connectivity patterns are thought to persist across task states, suggesting task‐based fMRI can be similarly leveraged for individual differences analyses. Method Here, we tested the degree to which functional interactions occurring in the background of a task during slow event‐related fMRI parallel or differ from those captured during resting‐state fMRI. We compared two approaches for removing task‐evoked activity from task‐based fMRI: (1) applying a low‐pass filter to remove task‐related frequencies in the signal, or (2) extracting residuals from a general linear model (GLM) that accounts for task‐evoked responses. Result We found that the organization of large‐scale cortical networks and individual's idiosyncratic connectivity patterns are preserved during task‐based fMRI. In contrast, individual differences in connection strength can vary more substantially between rest and task. Compared to low‐pass filtering, background connectivity obtained from GLM residuals produced idiosyncratic connectivity patterns and individual differences in connection strength that more resembled rest. However, all background connectivity measures were highly similar when derived from the low‐pass‐filtered signal or GLM residuals, indicating that both methods are suitable for measuring background connectivity. Conclusion Together, our results highlight new avenues for the analysis of task‐based fMRI datasets and the utility of each background connectivity method. In this manuscript, we measured the similarity of resting‐state connectivity profiles to those obtained during slow event‐related functional magnetic resonance imaging (fMRI). Importantly, background connectivity relies on the removal of task‐evoked signals to isolate intrinsic functional interactions. Here, we compared two common methods for removing task‐evoked activity: (1) applying a low‐pass filter to the fMRI time‐series signal, or (2) extracting the residuals from a general linear model of task‐evoked responses.

Studies in school-aged children and adults consistently implicate hippocampus, cortical regions, and their interaction as being critical for memory. However, few studies have examined this neural network in younger children (<8 years), despite the fact that behavioral studies consistently report substantial improvements in memory earlier in life. This study aimed to fill this gap by integrating task-based (i.e., memory encoding task) and task-free fMRI scans in 4- to 8-year-old children. Results showed that during memory encoding the hippocampus and several cortical regions (e.g., inferior frontal gyrus, IFG) were activated, consistent with findings in older individuals. Novel findings during memory encoding showed: 1) additional regions (i.e., orbital frontal gyrus, OFG) were recruited, 2) hippocampal activation varied due to age and performance, and 3) differentiation of connectivity between hippocampal subregions and IFG was greater in older versus younger participants, implying increased speicalization with age. Novel findings from task-free fMRI data suggested the extent of functional differentiation along the longitudinal axis of the hippocampus, particularly between hippocampus and OFG, was moderated by both age and performance. Our findings support and extend previous research, suggesting that maturation of hippocampal activity, connectivity, and differentiation may all contribute to development of memory during early childhood. •Episodic memory in early childhood depends on hippocampus and cortical regions.•Connectivity from hippocampus to cortical regions is critical for episodic memory.•Differentiation along the long axis of the hippocampus supports episodic memory.•Both age and performance relate to hippocampal function.•Brain bases of episodic memory in early childhood support component process model.

While many of the movements we make throughout our day involve just one upper limb, most daily movements require a certain degree of coordination between both upper limbs. Historically, sex differences in eye-hand coordination have been observed. As well, there are demonstrated sex-specific differences in hemisphere symmetry, interhemispheric connectivity, and motor cortex organization. While it has been suggested that these anatomical differences may underlie sex-related differences in performance, sex differences in the functional neural correlate underlying bimanual performance have not been explicitly investigated. In the current study we tested the hypothesis that the functional connectivity underlying bimanual movement control differed depending on the sex of an individual. Participants underwent MRI scanning to acquire anatomical and functional brain images. During the functional runs, participants performed unimanual and bimanual coordination tasks using two button boxes. The tasks included pressing the buttons in time to an auditory cue with either their left or their right hand individually (unimanual), or with both hands simultaneously (bimanual). The bimanual task was further divided into either an in-phase (mirror/symmetrical) or anti-phase (parallel/asymmetrical) condition. Participants were provided with extensive training to ensure task comprehension, and performance error rates were found to be equivalent between men and women. A generalized psychophysiological interaction (gPPI) analysis was implemented to examine how functional connectivity in each condition was modulated by sex. In support of our hypothesis, women and men demonstrated differences in the neural correlates underlying unimanual and bimanual movements. In line with previous literature, functional connectivity patterns showed sex-related differences for right- vs left-hand movements. Sex-specific functional connectivity during bimanual movements was not a sum of the functional connectivity underlying right- and left-hand unimanual movements. Further, women generally showed greater interhemispheric functional connectivity across all conditions compared to men and had greater connectivity between task-related cortical areas, while men had greater connectivity involving the cerebellum. Sex differences in brain connectivity were associated with both unimanual and bimanual movement control. Not only do these findings provide novel insight into the fundamentals of how the brain controls bimanual movements in both women and men, they also present potential clinical implications on how bimanual movement training used in rehabilitation can best be tailored to the needs of individuals.

•Longitudinal change in task-based functional connectivity was investigated across the lifespan in the reference ability neural network (RANN) cohort.•Topological data analysis (TDA) was compared to whole-brain system segregation with respect to age-related decline.•TDA measure displayed age-related longitudinal decreases for fluid reasoning whereas system segregation displayed age-related longitudinal decreases in Memory, fluid Reasoning, and processing speed.•When investigating the link between connectivity and behavior, only the TDA measure significantly predicted longitudinal cognitive change in the fluid reasoning domain.•The longitudinal TDA measure mediated the effect of age on longitudinal change in cognition again for the fluid reasoning domain. Recent attention has been given to topological data analysis (TDA), and more specifically persistent homology (PH), to identify the underlying shape of brain network connectivity beyond simple edge pairings by computing connective components across different connectivity thresholds (see Sizemore et al., 2019). In the present study, we applied PH to task-based functional connectivity, computing 0-dimension Betti (B0) curves and calculating the area under these curves (AUC); AUC indicates how quickly a single connected component is formed across correlation filtration thresholds, with lower values interpreted as potentially analogous to lower whole-brain system segregation (e.g., Gracia-Tabuenca et al., 2020). One hundred sixty-three participants from the Reference Ability Neural Network (RANN) longitudinal lifespan cohort (age 20–80 years) were tested in-scanner at baseline and five-year follow-up on a battery of tests comprising four domains of cognition (i.e., Stern et al., 2014). We tested for 1.) age-related change in the AUC of the B0 curve over time, 2.) the predictive utility of AUC in accounting for longitudinal change in behavioral performance and 3.) compared system segregation to the PH approach. Results demonstrated longitudinal age-related decreases in AUC for Fluid Reasoning, with these decreases predicting longitudinal declines in cognition, even after controlling for demographic and brain integrity factors; moreover, change in AUC partially mediated the effect of age on change in cognitive performance. System segregation also significantly decreased with age in three of the four cognitive domains but did not predict change in cognition. These results argue for greater application of TDA to the study of aging.

There are a limited number of neuroimaging investigations into motor control of the lumbopelvic musculature. Most investigation examining motor control of the lumbopelvic musculature utilize transcranial magnetic stimulation and focus primarily on the motor cortex. This has resulted in a dearth of knowledge as it relates to how other regions of the brain activate during lumbopelvic movement. Additionally, task-based functional connectivity during lumbopelvic movements has not been well elucidated. Therefore, we used functional magnetic resonance imaging (fMRI) to examine brain activation and ROI-to-ROI task-based functional connectivity in 19 healthy individuals (12 female, age 29.8 ± 4.5 years) during the performance of three lumbopelvic movements: modified bilateral bridge, left unilateral bridge, and right unilateral bridge. The whole brain analysis found robust, bilateral activation within the motor regions of the brain during the bilateral bridge task, and contralateral activation of the motor regions during unilateral bridging tasks. Furthermore, the ROI-to-ROI analysis demonstrated significant connectivity of a motor network that included the supplemental motor area, bilateral precentral gyrus, and bilateral cerebellum regardless of the motor task performed. These data suggest that while whole brain activation reveals unique patterns of activation across the three tasks, functional connectivity is very similar. As motor control of the lumbopelvic area is of high interest to those studying low back pain, this study can provide a comparison for future research into potential connectivity changes that occur in individuals with low back pain.

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of the occipital lobe affects the results of fMRI retinotopic mapping. fMRI data were evaluated on a retrospectively selected sample of 12 patients with occipital brain tumors, 7 patients with brain lesions and 19 control subjects. Analyses of the cortical activation, percent signal change, cluster size of the activated voxels and functional connectivity were carried out using Statistical Parametric Mapping (SPM12) and the CONN and Marsbar toolboxes. We found similar but reduced patterns of cortical activation and functional connectivity between the two patient groups compared to a healthy control group. Here, we found that retinotopic organization was well-preserved in the patients and was comparable to that of the age-matched controls. The results also showed that, compared to the tumor patients, the lesion patients showed higher percent signal changes but lower values in the cluster sizes of the activated voxels in the calcarine fissure region. Our results suggest that the lesion patients exhibited results that were more similar to those of the control subjects in terms of the BOLD signal, whereas the extent of the activation was comparable to that of the tumor patients.

The interpretation of fMRI data in glioblastoma (GB) is challenging as these tumors exhibit specific hemodynamic processes which, together with malignancy, tumor volume and proximity to eloquent cortex areas, may lead to misinterpretations of fMRI signals. The aim of this study was to investigate if different radiologically defined GB tumor growth patterns may also influence the fMRI signal, activation pattern and functional connectivity differently. Sixty-four patients with left-hemispheric glioblastoma were included and stratified according to their radiologically defined tumor growth pattern into groups with a uniform (U-TGP) or diffuse tumor growth pattern (D-TGP). Task-based fMRI data were analyzed using SPM12 with the marsbar, LI and CONN toolboxes. The percent signal change and the laterality index were analyzed, as well as functional connectivity between 23 selected ROIs. Comparisons of both patient groups showed only minor non-significant differences, indicating that the tumor growth pattern is not a relevant influencing factor for fMRI signal. In addition to these results, signal reductions were found in areas that were not affected by the tumor underlining that a GB is not a localized but rather a systemic disease affecting the entire brain.

Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the motor cortex. The relation between functional activity of motor cortex and symptom severity during a hand-grip motor control in vivo has not yet been investigated. This study explored both functional changes in the sensorimotor cortex and cerebellar regions and structural alterations in the cerebellum for SCA6 patients as compared to age-matched healthy controls using a multimodal imaging approach (task-based fMRI, task-based functional connectivity, and free-water diffusion MRI). Further, we tested their relation with the severity of ataxia symptoms. SCA6 patients had reduced functional activity in the sensorimotor cortex, supplementary motor area (SMA), cerebellar vermis, and cerebellar lobules I-VI (corrected P  < 0.05). Reduced task-based functional connectivity between cortical motor regions (i.e., primary motor cortex and SMA) and cerebellar regions (i.e., vermis and lobules I–VI) was found in SCA6 (corrected P  < 0.05). SCA6 had elevated free-water values throughout the cerebellum as compared with controls (corrected P  < 0.05). Importantly, reduced functional activity in the sensorimotor cortex and SMA and increased free-water in the superior cerebellar peduncle and cerebellar lobule V were related to more severe symptoms in SCA6 (all pairs: R 2  ≥ 0.4 and corrected P  < 0.05). Current results demonstrate that impaired functional activity in sensorimotor cortex and SMA and elevated free-water of lobule V and superior cerebellar peduncle are both related to symptom severity, and may provide candidate biomarkers for SCA6.

Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.

Background Motor imagery training (MIT) has been widely used to improve hemiplegic upper limb function in stroke rehabilitation. The effectiveness of MIT is associated with the functional neuroplasticity of the motor network. Currently, brain activation and connectivity changes related to the motor recovery process after MIT are not well understood. Aim: We aimed to investigate the neural mechanisms of MIT in stroke rehabilitation through a longitudinal intervention study design with task‐based functional magnetic resonance imaging (fMRI) analysis. Methods We recruited 39 stroke patients with moderate to severe upper limb motor impairment and randomly assigned them to either the MIT or control groups. Patients in the MIT group received 4 weeks of MIT therapy plus conventional rehabilitation, while the control group only received conventional rehabilitation. The assessment of Fugl‐Meyer Upper Limb Scale (FM‐UL) and Barthel Index (BI), and fMRI scanning using a passive hand movement task were conducted on all patients before and after treatment. The changes in brain activation and functional connectivity (FC) were analyzed. Pearson's correlation analysis was conducted to evaluate the association between neural functional changes and motor improvement. Results The MIT group achieved higher improvements in FM‐UL and BI relative to the control group after the treatment. Passive movement of the affected hand evoked an abnormal bilateral activation pattern in both groups before intervention. A significant Group × Time interaction was found in the contralesional S1 and ipsilesional M1, showing a decrease of activation after intervention specifically in the MIT group, which was negatively correlated with the FM‐UL improvement. FC analysis of the ipsilesional M1 displayed the motor network reorganization within the ipsilesional hemisphere, which correlated with the motor score changes. Conclusions MIT could help decrease the compensatory activation at both hemispheres and reshape the FC within the ipsilesional hemisphere along with functional recovery in stroke patients. The neural mechanism of motor imagery training in stroke patients with moderate to severe upper limb motor impairments was investigated using task‐based fMRI. The results revealed that motor imagery training during motor recovery decreased overaction at both hemispheres and reorganized the motor network within the ipsilesional hemisphere.