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Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

Resting-state functional MRI (fMRI) has revealed functional changes at the cortical level in degenerative cervical myelopathy (DCM) patients. The aim of this study was to systematically integrate static and dynamic functional connectivity (FC) to unveil abnormalities of functional networks of DCM patients and to analyze the prognostic value of these abnormalities for patients using resting-state fMRI. In this study, we collected clinical data and fMRI data from 44 DCM patients and 39 healthy controls (HC). Independent component analysis (ICA) was performed to investigate the group differences of intra-network FC. Subsequently, both static and dynamic FC were calculated to investigate the inter-network FC alterations in DCM patients. k-means clustering was conducted to assess temporal properties for comparison between groups. Finally, the support vector machine (SVM) approach was performed to predict the prognosis of DCM patients based on static FC, dynamic FC, and fusion of these two metrics. Relative to HC, DCM patients exhibited lower intra-network FC and higher inter-network FC. DCM patients spent more time than HC in the state in which both patients and HC were characterized by strong inter-network FC. Both static and dynamic FC could successfully classify DCM patients with different surgical outcomes. The classification accuracy further improved after fusing the dynamic and static FC for model training. In conclusion, our findings provide valuable insights into the brain mechanisms underlying DCM neuropathology on the network level. [ABSTRACT FROM AUTHOR]

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right‐handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right‐handed). In the TLE group, the presumed seizure onset zone was left‐sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre‐assessment. During a pre‐testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five‐point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two‐sided Mann–Whitney U tests, FDR‐p < 0.05) and less familiar (two‐sided Mann–Whitney U tests, FDR‐p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two‐sided Mann–Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io). [ABSTRACT FROM AUTHOR]

A growing number of publicly available human functional magnetic resonance imaging (fMRI) data sets use a 'deep' sampling approach, where many hours of data are acquired from a few individuals. We highlight an emerging approach within deep fMRI, which we refer to as 'intensive' fMRI: the creation of large-scale, publicly shared data sets that extensively sample cognitive phenomena to support the investigation of brain function at the single voxel level. We discuss key principles of intensive fMRI, its benefits and challenges, and practical considerations in creating intensive fMRI data sets. We discuss how intensive fMRI can advance scientific discovery in systems neuroscience, machine learning, and artificial intelligence. The rise of large, publicly shared functional magnetic resonance imaging (fMRI) data sets in human neuroscience has focused on acquiring either a few hours of data on many individuals ('wide' fMRI) or many hours of data on a few individuals ('deep' fMRI). In this opinion article, we highlight an emerging approach within deep fMRI, which we refer to as 'intensive' fMRI: one that strives for extensive sampling of cognitive phenomena to support computational modeling and detailed investigation of brain function at the single voxel level. We discuss the fundamental principles, trade-offs, and practical considerations of intensive fMRI. We also emphasize that intensive fMRI does not simply mean collecting more data: it requires careful design of experiments to enable a rich hypothesis space, optimizing data quality, and strategically curating public resources to maximize community impact. [ABSTRACT FROM AUTHOR]

It is known that abnormal functional connectivity (FC) in schizophrenia (SZ) is closely related to structural connectivity (SC). We speculate that indirect SC also have an impact on FC in SZ patients. Conventional single-layer network has limitations for studying the relationship between indirect SC and FC. Thus, this study constructed a multiplex network based on structural connectivity and functional connectivity (SC-FC). The SC-FC bandwidth and SC-FC cost are used to analyze the impact of indirect SC on FC. Moreover, this paper proposed mediation ability, mediation cost, mediated strength and mediated cost to quantify the effects of mediator nodes and mediated nodes on indirect SC. The results show that SZ patients exhibit lower SC-FC bandwidth and SC-FC cost compared to healthy controls (HC), which could be caused by the limbic and subcortical network (LSN), default mode network (DMN) and visual network (VN). The mediator and mediated nodes in indirect SC of SZ patients also showed diminished effects. These findings suggest that functional communication ability and cost in SZ patients are influenced by indirect SC. This study provides new perspectives for understanding the relationship between indirect SC and FC, and provides strong evidence for interpreting the physiological mechanisms of SZ patients. • Construction of multiplex network based on structural connectivity (SC) and functional connectivity (FC). • Using SC-FC bandwidth and SC-FC cost to analyze how indirect SC affects FC. • The SC-FC bandwidth and SC-FC cost of SZ patients were significantly reduced at whole-brain and module levels. • The role of nodes in affecting FC was quantified from mediator and mediated perspectives. • Results suggest that indirect SC in SZ patients results in reduced functional communication ability and cost. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to explore the functional connectivity (FC) of the cerebellum during the storage phase of micturition, through detecting spontaneous blood‐oxygen‐level dependent signal between the cerebellum and different brain regions using a high‐resolution 7 Tesla magnetic resonance imaging (MRI) scanner. Materials and Methods: We recruited healthy individuals with no reported history of neurological disease or lower urinary tract (LUT) symptoms. Participants were asked to drink 500 mL of water and then empty their bladders before entering the MRI scanner. They underwent a T1‐weighted anatomical scan, followed by an initial (8 min) empty bladder resting state functional MRI (rs‐fMRI) acquisition. Once subjects felt the desire to void, a second rs‐fMRI scan was obtained, this time with a full bladder state. We established a priori cerebellar regions of interest from the literature to perform seed‐to‐voxel analysis using nonparametric statistics based on the Threshold Free Cluster Enhancement method and utilized a voxel threshold of p < 0.05. Results: Twenty individuals (10 male and 10 female) with a median age of 25 years (IQR [3.5]) participated in the study. We placed 31 different 4‐mm spherical seeds throughout the cerebellum and assessed their FC with the remainder of the brain. Three of these (left cerebellar tonsil, right posterolateral lobe, right posterior lobe) showed significant differences in connectivity when comparing scans conducted with a full bladder to those with an empty bladder. Additionally, we observed sex differences in FC, with connectivity being higher in women during the empty bladder condition. Conclusion: Our initial findings reveal, for the first time, that the connectivity of the cerebellar network is modulated by bladder filling and is associated with LUT function. Unraveling the cerebellum's role in bladder function lays the foundation for a more comprehensive understanding of urinary pathologies affecting this area. [ABSTRACT FROM AUTHOR]

Background: There are increasing reports of the misuse of prescription psychostimulants for cognitive enhancement together with recreational cannabis. This raises a concern that chronic use of cannabis high in Δ9-THC may alter the sensitivity to amphetamines. In this exploratory study we hypothesized chronic exposure to Δ9-THC through vaporized cannabis would diminish the central nervous system (CNS) activity of Adderall. Methods: To address this issue we exposed male and female mice to inhaled vaporized cannabis (10.3% Δ9-THC) or placebo for 30 min each day for ten consecutive days. After 24 h, mice were imaged fully awake for changes in BOLD signal following an IP injection of Adderall (60 µg) during the scanning session. After a 2-week washout, without any cannabis or placebo exposure, mice were again imaged and challenged with Adderall during the scanning session. The data were registered to a mouse 3D MRI atlas with 134 brain regions providing sitespecific increases and decreases in global brain activity. Results: Mice exposed to cannabis when compared to placebo showed a decrease in brain activation to Adderall. The blunted Adderall response was characterized by a decrease in positive BOLD signal and increase in negative BOLD. The prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus were most affected. After a 2-week wash out there were no significant differences between the cannabis and placebo groups when challenged with Adderall. Summary: This exploratory study shows that short, daily exposures to inhaled cannabis, something equivalent to recreational use, affects the sensitivity to the psychostimulant Adderall. The reduced Adderall effect on brain activity, particularly circuitry associated with dopaminergic signaling raises concerns about escalation in psychostimulant use. [ABSTRACT FROM AUTHOR]

Background: Working memory (WM), a core component of executive functions, relies on a dedicated brain system that maintains and stores information in the short term. While extensive neuroimaging research has identified a distributed set of neural substrates relevant to WM, their underlying molecular mechanisms remain enigmatic. This study investigated the neural correlates of WM as well as their underlying molecular mechanisms. Results: Our voxel-wise analyses of resting-state functional MRI data from 502 healthy young adults showed that better WM performance (higher accuracy and shorter reaction time of the 3-back task) was associated with lower functional connectivity density (FCD) in the left inferior temporal gyrus and higher FCD in the left anterior cingulate cortex. A combination of transcriptome-neuroimaging spatial correlation and the ensemble-based gene category enrichment analysis revealed that the identified neural correlates of WM were associated with expression of diverse gene categories involving important cortical components and their biological processes as well as sodium channels. Cross-region spatial correlation analyses demonstrated significant associations between the neural correlates of WM and a range of neurotransmitters including dopamine, glutamate, serotonin, and acetylcholine. Conclusions: These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM. [ABSTRACT FROM AUTHOR]

Long‐term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting‐state networks for predicting short and long‐term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting‐state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default‐mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long‐term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital‐3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M–12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long‐term memory, attention, or executive functioning. Resting‐state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short‐term global, but not long‐term global or domain‐specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long‐term cognitive performance after cardiac arrest. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia is characterized by a loss of network features between cognition and reward sub-circuits (notably involving the mesolimbic system), and this loss may explain deficits in learning and cognition. Learning in schizophrenia has typically been studied with tasks that include reward related contingencies, but recent theoretical models have argued that a loss of network features should be seen even when learning without reward. We tested this model using a learning paradigm that required participants to learn without reward or feedback. We used a novel method for capturing higher order network features, to demonstrate that the mesolimbic system is heavily implicated in the loss of network features in schizophrenia, even when learning without reward. Methods: fMRI data (Siemens Verio 3T) were acquired in a group of schizophrenia patients and controls (n=78; 46 SCZ, 18 = Age = 50) while participants engaged in associative learning without reward-related contingencies. The task was divided into task-active conditions for encoding (of associations) and cued-retrieval (where the cue was to be used to retrieve the associated memoranda). No feedback was provided during retrieval. From the fMRI time series data, network features were defined as follows: First, for each condition of the task, we estimated 2nd order undirected functional connectivity for each participant (uFC, based on zero lag correlations between all pairs of regions). These conventional 2nd order features represent the task/condition evoked synchronization of activity between pairs of brain regions. Next, in each of the patient and control groups, the statistical relationship between all possible pairs of 2nd order features were computed. These higher order features represent the consistency between all possible pairs of 2nd order features in that group and embed within them the contributions of individual regions to such group structure. Results: From the identified inter-group differences (SCZ - HC) in higher order features, we quantified the respective contributions of individual brain regions. Two principal effects emerged: 1) SCZ were characterized by a massive loss of higher order features during multiple task conditions (encoding and retrieval of associations). 2) Nodes in the mesolimbic system were over-represented in the loss of higher order features in SCZ, and notably so during retrieval. Discussion: Our analytical goals were linked to a recent circuit-based integrative model which argued that synergy between learning and reward circuits is lost in schizophrenia. Themodel's notable prediction was that such a losswould be observed evenwhen patients learnedwithout reward. Our results provide substantial support for these predictions where we observed a loss of network features between the brain's sub-circuits for a) learning (including the hippocampus and prefrontal cortex) and b) reward processing (specifically constituents of the mesolimbic system that included the ventral tegmental area and the nucleus accumbens. Our findings motivate a renewed appraisal of the relationship between reward and cognition in schizophrenia and we discuss their relevance for putative behavioral interventions. [ABSTRACT FROM AUTHOR]

Objective: To determine the safety and proof of concept of a parcel-guided, repetitive Transcranial Magnetic Stimulation (rTMS) in patients who develop a heterogeneous array of symptoms, known collectively as post-concussive syndrome (PCS), following traumatic brain injury (TBI). Methods: We performed a retrospective review of off-label, individualized, parcel-guided rTMS in 19 patients from December 2020 to May 2023. Patients had at least one instance of mild, moderate, or severe TBI and developed symptoms not present prior to injury. rTMS targets were identified based on machine learning connectomic software using functional connectivity anomaly matrices compared to healthy controls. EuroQol (EQ-5D), as a measurement of quality of life, and additional questionnaires dependent on individual's symptoms were submitted prior to, after, and during follow-up from rTMS. Results: Nineteen patients showed improvement in EQ-5D and Rivermead Post Concussion Symptoms Questionnaires − 3 after treatment and follow-up. For nine patients who developed depression, five (55%) attained response and remission based on the Beck Depression Inventory after treatment. Eight of ten patients with anxiety had a clinically significant reduction in Generalized Anxiety Disorder-7 scores during follow-up. Conclusion: Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies. [ABSTRACT FROM AUTHOR]

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide corroborative data on neurophysiological alterations in Huntington's disease (HD). However, the alterations in EEG and fMRI resting-state functional connectivity (rsFC), as well as their interrelations, at different stages of HD remain insufficiently investigated. This study aimed to identify neurophysiological alterations in individuals with preclinical HD (preHD) and early manifest HD (EMHD) by analyzing EEG and fMRI rsFC and examining their interrelationships. We found significant differences in EEG power between preHD individuals and healthy controls (HC), with a decrease in power in a specific frequency range at the theta-alpha border and slow alpha activity. In EMHD patients, in addition to the decrease in power in the 7--9 Hz range, a reduction in power within the classic alpha band compared to HC was observed. The fMRI analysis revealed disrupted functional connectivity in various brain networks, particularly within frontal lobe, putamen-cortical, and cortico-cerebellar networks, in individuals with the HD mutation compared to HC. The analysis of the relationship between EEG and fMRI rsFC revealed an association between decreased alpha power, observed in individuals with EMHD, and increased connectivity in large-scale brain networks. These networks include putamen-cortical, DMN-related and cortico-hippocampal circuits. Overall, the findings suggest that EEG and fMRI provide valuable information for monitoring pathological processes during the development of HD. A decrease in inhibitory control within the putamen-cortical, DMN-related and cortico-hippocampal circuits, accompanied by a reduction in alpha and theta-alpha border oscillatory activity, could potentially contribute to cognitive decline in HD. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. Methods: Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. Results: Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P < 0.05). The FNC analysis between different RSNs also provides evidence on visual-motor cortical plasticity. Conclusions: IXT patients showed widespread changes of brain activity within RSNs related to binocular fusion, stereopsis, oculomotor control, emotional processes, and social cognition. These findings extend our current understanding of the neuropathological mechanisms of IXT. Trial registration: Beginning date of the trial: 2021-09-01. Date of registration:2021-07-18. Trial registration number: ChiCTR 2,100,048,852. Trial registration site: http://www.chictr.org.cn/index.aspx. [ABSTRACT FROM AUTHOR]

To test a Chinese character version of the phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE) and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis, a cross-sectional study was conducted including 30 patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC). Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of the left frontal and temporal regions were compared. A neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k≥10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under the curve of 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS. [ABSTRACT FROM AUTHOR]

Objective: To use intracranial electroencephalography (EEG) to characterize functional magnetic resonance imaging (fMRI) activation maps associated with high‐frequency oscillations (HFOs) (80–250 Hz) and examine their proximity to HFO‐ and seizure‐generating tissue. Methods: Forty‐five patients implanted with intracranial depth electrodes underwent a simultaneous EEG‐fMRI study at 3 T. HFOs were detected algorithmically from cleaned EEG and visually confirmed by an experienced electroencephalographer. HFOs that co‐occurred with interictal epileptiform discharges (IEDs) were subsequently identified. fMRI activation maps associated with HFOs were generated that occurred either independently of IEDs or within ±200 ms of an IED. For all significant analyses, the Maximum, Second Maximum, and Closest activation clusters were identified, and distances were measured to both the electrodes where the HFOs were observed and the electrodes involved in seizure onset. Results: We identified 108 distinct groups of HFOs from 45 patients. We found that HFOs with IEDs produced fMRI clusters that were closer to the local field potentials of the corresponding HFOs observed within the EEG than HFOs without IEDs. In addition to the fMRI clusters being closer to the location of the EEG correlate, HFOs with IEDs generated Maximum clusters with greater z‐scores and larger volumes than HFOs without IEDs. We also observed that HFOs with IEDs resulted in more discrete activation maps. Significance: Intracranial EEG‐fMRI can be used to probe the hemodynamic response to HFOs. The hemodynamic response associated with HFOs that co‐occur with IEDs better identifies known epileptic tissue than HFOs that occur independently. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) patients are impaired in word production when the word has to be selected among competing alternatives requiring higher attentional resources. In PD, word selection processes are correlated with the structural integrity of the inferior frontal gyrus, which is critical for response selection, and the uncinate fasciculus, which is necessary for processing lexical information. In early PD, we investigated the role of the main cognitive large-scale networks, namely the salience network (SN), the central executive networks (CENs), and the default mode network (DMN), in word selection. Eighteen PD patients and sixteen healthy controls were required to derive nouns from verbs or generate verbs from nouns. Participants also underwent a resting-state functional MRI. Functional connectivity (FC) was examined using independent component analysis. Functional seeds for the SN, CENs, and DMN were defined as spheres, centered at the local activation maximum. Correlations were calculated between the FC of each functional seed and word production. A significant association between SN connectivity and task performance and, with less evidence, between CEN connectivity and the task requiring selection among a larger number of competitors, emerged in the PD group. These findings suggest the involvement of the SN and CEN in word selection in early PD, supporting the hypothesis of impaired executive control. [ABSTRACT FROM AUTHOR]

Purpose: To objectively assess visual function in Leber's Hereditary Optic Neuropathy (LHON) patients; this study evaluated pre- and post-idebenone treatment changes in primary visual cortical (V1) responses using functional magnetic resonance imaging (fMRI), given the challenges in subjective testing due to central retinal ganglion cell damage. Study design: A descriptive study involving four confirmed LHON patients. Methods: Four patients received 900 mg/day of oral idebenone for 24 weeks. Baseline and post-treatment visual acuity, visual fields, and BOLD fMRI responses while passively viewed drifting contrast pattern visual stimuli were compared with self-reported symptoms. Results: Post-idebenone, one patient showed positive trends across subjective tests, reported symptoms, and fMRI. Two patients had stable symptoms and fMRI responses; one improved on subjective tests, and another worsened slightly. Another patient improved in visual field tests despite worsening symptoms and fMRI trends. Conclusion: fMRI may offer a valuable objective measure of visual functions in LHON and appears to be more relevant in assessing symptoms. Further research with more participants is needed to ascertain fMRI's role in developing objective visual assessments and treatment evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background Working memory (WM), a core component of executive functions, relies on a dedicated brain system that maintains and stores information in the short term. While extensive neuroimaging research has identified a distributed set of neural substrates relevant to WM, their underlying molecular mechanisms remain enigmatic. This study investigated the neural correlates of WM as well as their underlying molecular mechanisms. Results Our voxel-wise analyses of resting-state functional MRI data from 502 healthy young adults showed that better WM performance (higher accuracy and shorter reaction time of the 3-back task) was associated with lower functional connectivity density (FCD) in the left inferior temporal gyrus and higher FCD in the left anterior cingulate cortex. A combination of transcriptome-neuroimaging spatial correlation and the ensemble-based gene category enrichment analysis revealed that the identified neural correlates of WM were associated with expression of diverse gene categories involving important cortical components and their biological processes as well as sodium channels. Cross-region spatial correlation analyses demonstrated significant associations between the neural correlates of WM and a range of neurotransmitters including dopamine, glutamate, serotonin, and acetylcholine. Conclusions These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM.

Background: Non-specific chronic low back pain (CLBP) is a common painful condition and is responsible for different physical disorders. Despite alternative therapies, patients still suffer from persistent pain. Repetitive transcranial magnetic stimulation (rTMS) has provided much evidence of pain reduction, but results have not been examined deeply in CLBP symptoms.Objective: The analgesic effect of rTMS in non-specific CLBP patients was evaluated by the amplitude of low-frequency fluctuation (ALFF) analysis in resting-state fMRI.Material and Methods: In this experimental study, fifteen non-specific CLBP participants (46.87±10.89 years) received 20 Hz rTMS over the motor cortex. The pain intensity and brain functional scan were obtained during pre and post-stimulation for all participants. The ALFF maps of the brain in two scan sessions were identified and the percentage of pain reduction (PPR%) was determined using paired t-test. Also, correlation analysis was used to find a relationship between ALFFs and pain intensity.Results: Pain intensity was significantly reduced after induced-rTMS in non-specific CLBP (36.22%±13.28, P

Abstract Background The pathogenesis of intermittent exotropia (IXT) remains unclear. The study aims to investigate alterations of resting-state networks (RSNs) in IXT adult patients using resting-state functional magnetic resonance imaging (rs-fMRI) data to explore the potential neural mechanisms. Methods Twenty-six IXT adult patients and 22 age-, sex-, handedness-, and education-matched healthy controls (HCs) underwent fMRI scanning and ophthalmological examinations. Brain areas with significant functional connectivity (FC) differences between the IXT and HC groups were selected as regions of interest (ROI) and mean z-scores were calculated to control for individual differences. Results Compared with HCs, IXT patients exhibited altered FC in various brain regions within RSNs involved in binocular fusion, stereopsis, ocular movement, emotional processes and social cognition, including the default mode network (DMN), the dorsal attention network (DAN), the visual network (VN), the sensorimotor network (SMN), the executive control network (ECN), the frontoparietal network (FPN) and the auditory network (AN). The degree of exodeviation was positively correlated with FC value of left middle occipital gyrus (MOG) within the VN. Correspondingly, we found a negative correlation between the degree of exodeviation and the FC value of left angular gyrus (AG) within FPN (P

Borderline personality disorder (BPD) and complex posttraumatic stress disorder (cPTSD) share clinical similarities, complicating diagnosis and treatment. Research on the neurobiology of BPD and monotraumatic PTSD has shown that a prefrontal-limbic imbalance in emotional and reward processing is a hallmark of both disorders, but studies examining this network in cPTSD are lacking. Therefore, this study aimed to directly compare neural processing of emotion and reward during decision making in cPTSD and BPD. Using functional magnetic resonance imaging, we measured neural activity in female patients (27 patients with cPTSD, 21 patients with BPD and 37 healthy controls) during a Desire-Reason Dilemma task featuring distracting fearful facial expressions. We found no differences in neural activation when comparing cPTSD and BPD. However, when grouping patients based on symptom severity instead on diagnosis, we found that increased symptoms of cPTSD were associated with increased activation of dorsolateral prefrontal cortex during reward rejection, whereas increased symptoms of BPD were associated with decreased activation in prefrontal and limbic regions during reward rejection with distracting negative emotional stimuli. This is the first study to investigate and compare emotional processing and reward-based decision making in cPTSD and BPD. Although we found no neural differences between disorders, we identified symptom-related neural patterns. Specifically, we found that elevated cPTSD symptoms were related to greater sensitivity to reward stimuli, whereas heightened BPD symptoms were related to increased susceptibility to emotional stimuli during goal-directed decision making. These findings enhance our understanding of neural pathomechanisms in trauma-related disorders. • First study to compare emotional processing and reward-based decision making in cPTSD and BPD. • Neural processing of rewards and emotions differs according to symptom severity rather than diagnostic status. • Symptoms of cPTSD are associated with increased cognitive control during reward rejection. • Symptoms of BPD are associated with increased emotional interference during inhibitory processing. [ABSTRACT FROM AUTHOR]

Childhood neglect is associated with brain changes, yet the molecular mechanisms and behavioral relevance underlying such associations remain elusive. We calculated fractional amplitude of low-frequency fluctuations (fALFF) using resting-state functional MRI and tested their correlation with childhood neglect across a large sample of 510 healthy young adults. Then, we investigated the spatial relationships of the identified neural correlates of childhood neglect with gene expression, neurotransmitter, and behavioral domain atlases. We found that more severe childhood neglect was correlated with higher fALFF in the bilateral anterior cingulate cortex. Remarkably, the identified neural correlates of childhood neglect were spatially correlated with expression of gene categories primarily involving neuron, synapse, ion channel, cognitive and perceptual processes, and physiological response and regulation. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including serotonin and GABA. Finally, neural correlates of childhood neglect were associated with diverse behavioral domains implicating mental disorders, emotion, cognition, and sensory perception. The cross-sectional study design cannot unequivocally establish causality. Our findings may not only add to the current knowledge regarding the relationship between childhood neglect and mental health, but also have clinical implications for developing preventive strategies for individuals exposed to childhood neglect who are at risk for mental disorders. • Our work investigated neural correlates of childhood neglect and their molecular mechanisms and behavioral relevance. • More severe childhood neglect was correlated with higher fALFF in the bilateral anterior cingulate cortex. • The neural correlates of neglect were linked to specific gene category expressions, neurotransmitter systems, and behavior. • These findings may add to the current knowledge regarding the relationship between childhood neglect and mental health. [ABSTRACT FROM AUTHOR]

Background: Clinical evidence supports that swallowing function is correlated with cognition, but the neurobiological mechanism associated with cognitive impairment and dysphagia remains unclear. Objectives: To compare the brain activation patterns of the swallowing and the cognitive tasks and explore neural associations between swallowing and cognitive function via task‐related functional magnetic resonance imaging (fMRI). Methods: A total of 13 healthy older adults (aged > 60 years) were recruited. Participants underwent the clinical dementia rating (CDR) test and the Montreal Cognitive Assessment (MoCA). A block‐designed task‐related fMRI study was conducted where each participant completed both swallowing and cognitive tasks within a single session. During the swallowing task, participants swallowed 2 mL of thickened water, while the Stroop Colour Word Test (SCWT) served as the cognitive task. First‐level analysis of swallowing time‐series images utilised the general linear model (GLM) with Statistical Parametric Mapping (SPM), applying a voxel threshold of p < 0.001 for significance. Common activations in brain regions during swallowing and cognitive tasks were extracted at the group level, with significance set at p < 0.05, corrected for multiple comparisons using the false discovery rate (FDR), with a minimum cluster size of 20 voxels. Correlation analysis between behavioural measurements and imaging signals was also conducted. Results: Some regions were commonly activated in both task networks; these regions were the bilateral occipital lobe, cerebellum, lingual gyrus, fusiform, middle frontal gyrus, precentral and postcentral gyrus, right supramarginal and inferior parietal lobe. Most importantly, the average beta value of cognitive and swallowing tasks in these areas are both significantly negative related to the MoCA score. Furthermore, opposite signal changes were seen in the bilateral prefrontal lobes during the swallowing task, while positive activation in the bilateral prefrontal lobes was observed during the SCWT. Postcentral gyrus activation was more extensive than precentral gyrus activation in the swallowing task. Conclusion: The common activation of swallowing and cognitive tasks had multiple foci. The activity of cognitive and swallowing task in these areas is significantly negative correlated with the MoCA score. These findings may help to illustrate the association between dysphagia and cognitive impairment due to the common brain regions involved in cognition and swallowing and may provide a reference for further rehabilitation of dysphagia. Trial Registration: Clinical Trial: (Chinese Clinical Trial Registry): ChiCTR1900021795 [ABSTRACT FROM AUTHOR]

Neurofeedback (NF) has emerged as a promising avenue for demonstrating process-related neuroplasticity, enabling self-regulation of brain function. NF targeting the amygdala has drawn attention to therapeutic potential in psychiatry, by potentially harnessing emotion-regulation processes. However, not all individuals respond equally to NF training, possibly owing to varying self-regulation abilities. This underscores the importance of understanding the mechanisms behind successful neuromodulation (i.e. capacity). This study aimed to investigate the establishment and neural correlates of neuromodulation capacity using data from repeated sessions of amygdala electrical fingerprint (Amyg-EFP)-NF and post-training functional magnetic resonance imaging (fMRI)-NF sessions. Results from 97 participants (healthy controls and post-traumatic stress disorder and fibromyalgia patients) revealed increased Amyg-EFP neuromodulation capacity over training, associated with post-training amygdala-fMRI modulation capacity and improvements in alexithymia. Individual differenaces in this capacity were associated with pre-training amygdala reactivity and initial neuromodulation success. Additionally, amygdala downregulation during fMRI-NF co-modulated with other regions such as the posterior insula and parahippocampal gyrus. This combined modulation better explained EFP-modulation capacity and improvement in alexithymia than the amygdala modulation alone, suggesting the relevance of this broader network to gained capacity. These findings support a network-based approach for NF and highlight the need to consider individual differences in brain function and modulation capacity to optimize NF interventions. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'. [ABSTRACT FROM AUTHOR]

Yue He,1,&ast; Qianhan Liu,1,&ast; Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Abstract Background Migraine has been associated with functional brain changes including altered connectivity and activity both during and between headache attacks. Recent studies established that the variability of the blood-oxygen-level-dependent (BOLD) signal is an important attribute of brain activity, which has so far been understudied in migraine. In this study, we investigate how time-varying measures of BOLD variability change interictally in episodic migraine patients. Methods Two independent resting state functional MRI datasets acquired on 3T (discovery cohort) and 1.5T MRI scanners (replication cohort) including 99 episodic migraine patients (n3T = 42, n1.5T=57) and 78 healthy controls (n3T = 46, n1.5T=32) were analyzed in this cross-sectional study. A framework using time-varying measures of BOLD variability was applied to derive BOLD variability states. Descriptors of BOLD variability states such as dwell time and fractional occupancy were calculated, then compared between migraine patients and healthy controls using Mann-Whitney U-tests. Spearman’s rank correlation was calculated to test associations with clinical parameters. Results Resting-state activity was characterized by states of high and low BOLD signal variability. Migraine patients in the discovery cohort spent more time in the low variability state (mean dwell time: p = 0.014, median dwell time: p = 0.022, maximum dwell time: p = 0.013, fractional occupancy: p = 0.013) and less time in the high variability state (mean dwell time: p = 0.021, median dwell time: p = 0.021, maximum dwell time: p = 0.025, fractional occupancy: p = 0.013). Higher uptime of the low variability state was associated with greater disability as measured by MIDAS scores (maximum dwell time: R = 0.45, p = 0.007; fractional occupancy: R = 0.36, p = 0.035). Similar results were observed in the replication cohort. Conclusion Episodic migraine patients spend more time in a state of low BOLD variability during rest in headache-free periods, which is associated with greater disability. BOLD variability states show potential as a replicable functional imaging marker in episodic migraine.

Abstract Background Recent scientific evidence has challenged the traditional “rest-is-best” approach for concussion management. It is now thought that “exercise-is-medicine” for concussion, owing to dozens of studies which demonstrate that sub-maximal, graded aerobic exercise can reduce symptom burden and time to symptom resolution. However, the primary neuropathology of concussion is altered functional brain activity. To date, no studies have examined the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion. In addition, although exercise is now more widely prescribed following concussion, its cardiopulmonary response is not yet well understood in this population. Our study has two main goals. The first is to understand whether there are exercise-induced resting state functional brain activity differences in children with concussion vs. healthy controls. The second is to profile the physiological response to exercise and understand whether it differs between groups. Methods We will perform a single-center, controlled, prospective cohort study of pediatric concussion at a large, urban children’s hospital and academic center. Children with sport-related concussion (aged 12–17 years) will be recruited within 4-weeks of injury by our clinical study team members. Key inclusion criteria include: medical clearance to exercise, no prior concussion or neurological history, and no implants that would preclude MRI. Age- and sex-matched healthy controls will be required to meet the same inclusion criteria and will be recruited through the community. The study will be performed over two visits separated by 24–48 h. Visit 1 involves exercise testing (following the current clinical standard for concussion) and breath-by-breath gas collection using a metabolic cart. Visit 2 involves two functional MRI (fMRI) scans interspersed by 10-minutes of treadmill walking at an intensity calibrated to Visit 1 findings. To address sub-objectives, all participants will be asked to self-report symptoms daily and wear a waist-worn tri-axial accelerometer for 28-days after Visit 2. Discussion Our study will advance the growing exercise-concussion field by helping us understand whether exercise impacts outcomes beyond symptoms in pediatric concussion. We will also be able to profile the cardiopulmonary response to exercise, which may allow for further understanding (and eventual optimization) of exercise in concussion management. Trial registration Not applicable.

Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, dry skin and persistent itch. AD may worsen due to psychological stress. However, little is known about the neural correlates that mediate the interaction between psychological stress and AD. Objectives To identify the possible difference in brain activation during arithmetic‐task induced stress in patients with AD versus healthy controls (HC) as well as the link between the brain response and clinical and psychodemographic parameters. Methods A cohort of 29 AD female patients and 23 matched HC were recruited to investigate the potential difference in functional magnetic resonance imaging (fMRI) response to a block‐designed arithmetic paradigm. Both the HC and AD subjects were evaluated regarding their psychological traits, and for the AD subjects also their clinical characteristics, including stress indicators such as heart rate and salivary cortisol. We employed both univariate and multivariate statistical methods to analyse the blood oxygen level dependent (BOLD) fMRI response of the subjects to the block‐designed arithmetic paradigm. Results (1) Compared with HC subjects, the AD patients depict less deactivation in the default mode network including right angular gyrus, bilateral temporal pole and temporal lobe in response to the arithmetic task. (2) The BOLD fMRI response amplitude in the right postcentral gyrus and inferior parietal lobule is positively correlated with the stress susceptibility scores in the AD subjects, whereas the trend was the opposite of this for the HC subjects. (3) The activation in the postcentral gyrus also shows a correlation with the degree of itch in the AD patients. Conclusions The BOLD fMRI measurements based on an arithmetic paradigm can provide useful insight into altered brain processing and its association with psychological traits and clinical characteristics in subjects with AD. Psychological stress exacerbates brain activities for the AD subjects in the motor, somatosensory association cortex, perception and sensory integration processing. The postcentral gyrus might be of particular interest for itch and stress.

Background: Acute ischemic stroke is a leading cause of morbidity and mortality worldwide. Early and accurate imaging is crucial for effective management and improving patient outcomes. Functional MRI (fMRI) and CT perfusion imaging (CTP) are two advanced imaging modalities used to assess ischemic lesions. This study aims to compare the effectiveness and accuracy of fMRI and CTP in acute stroke management. Objective: To compare the effectiveness and accuracy of fMRI and CTP in acute stroke management, focusing on early detection, lesion characterization, and outcome prediction. Methods: A prospective cohort study was conducted on 100 patients presenting with acute ischemic stroke within 6 hours of symptom onset. Each patient underwent both fMRI and CTP imaging. Key metrics assessed included time to image acquisition, sensitivity, specificity, lesion detection and characterization, and predictive value for functional outcomes measured by the modified Rankin Scale (mRS) at 90 days. Results: The mean time from patient arrival to image acquisition was 30 minutes (±5) for fMRI and 25 minutes (±4) for CTP (p < 0.05). Sensitivity for detecting ischemic lesions was 95% for fMRI and 90% for CTP, while specificity was 92% for fMRI and 88% for CTP (p < 0.05). fMRI detected 120 lesions compared to 110 by CTP and characterized penumbra versus core infarct in 90% of cases compared to 85% for CTP (p < 0.05). The correlation coefficient for predicting functional outcomes was 0.85 for fMRI and 0.80 for CTP (p < 0.01). Functional independence (mRS 0-2) was achieved in 60% of fMRI patients and 55% of CTP patients (p < 0.05). Conclusion: Both fMRI and CTP are effective in acute stroke management. However, fMRI showed higher sensitivity, specificity, superior lesion detection and characterization, and better predictive value for functional outcomes. fMRI may be a more reliable tool for early stroke assessment, though CTP remains a valuable alternative when fMRI is not available. [ABSTRACT FROM AUTHOR]

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self‐reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl‐Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB‐AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by.40 and 3.70 points from baseline to 1‐week and 6‐month post‐surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1‐week post‐surgery, although partially recurred at 6‐month follow‐up. The average scores of WAB‐AQ were increased by 9.14 and 10.69 points at 1‐week and 6‐month post‐surgery (P <.001 for both), respectively. Post‐surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries. [ABSTRACT FROM AUTHOR]

The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI. However, stronger connectivity was observed in the cognitive cerebellar lobules with certain brain regions, including the precuneus cortex, posterior cingulate gyrus, and caudate nucleus in participants with worse cognition. Leveraging these measurable changes in cerebello-parietal functional networks in aMCI could offer avenues for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) syndrome, characterized by daytime impairment, affects approximately 1 in 20 adults and can lead to a range of behavioral and cardiovascular abnormalities. Understanding the underlying causes and identifying the specific obstructions within the upper airway is crucial for effective management of this condition. Sleep MRI has emerged as a valuable tool in accurately diagnosing OSA by providing detailed insights into the level, magnitude, and type of obstruction present in affected individuals. One of the key observations made through sleep MRI studies is the increased collapsibility of the velopharynx in apneic patients, particularly during sleep. This heightened collapsibility predisposes the airway to occlusion, contributing to the repetitive breathing pauses characteristic of OSA. By visualizing the dimensions and configurations of the upper airway during both wakefulness and sleep, sleep MRI enables clinicians to pinpoint structural and dynamic factors that play a role in the development and progression of OSA. Moreover, the information gleaned from sleep MRI scans can inform the development of personalized treatment strategies for OSA patients. By identifying specific anatomical abnormalities and dynamic changes in the upper airway, clinicians can tailor interventions such as continuous positive airway pressure (CPAP), oral appliances, or surgical procedures to address the underlying causes of obstruction more effectively. Sleep MRI serves as a powerful diagnostic tool in the management of OSA, offering detailed anatomical and functional insights that guide treatment planning and optimization. Its ability to uncover structural and dynamic factors contributing to airway obstruction enhances our understanding of OSA pathophysiology and facilitates targeted therapeutic interventions aimed at improving patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Summary: Light has many non‐image‐forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non‐image‐forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. In the present study, we aimed to characterise the task‐evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (mean [SD] 24.05 [4.0] years; 14 women) whilst they completed an attentional and an emotional auditory task whilst exposed to repeated 30–40‐s blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light (0.16 melanopic equivalent daylight illuminance (EDI) lux) or blue‐enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500 K]. For the analysis, 15 and then 14 participants were included in the attentional and emotional tasks, respectively. Generalised linear mixed models showed a significant main effect of light level on the task‐evoked pupil responses triggered by the attentional and emotional tasks (p ≤ 0.0001). The impact of light was different for the target versus non‐target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. There is a smaller sustained pupil size during brighter light blocks but, a higher light level triggers a stronger task‐evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus. [ABSTRACT FROM AUTHOR]

Background: Acupuncture, as an alternative and complementary therapy recommended by the World Health Organization for stroke treatment, holds potential in ameliorating neurofunctional deficits induced by ischemic stroke (IS). Understanding the immediate and long-term effects of acupuncture and their interrelation would contribute to a better comprehension of the mechanisms underlying acupuncture efficacy. Methods: Activation likelihood estimation (ALE) meta-analysis was used to analyze the brain activation patterns reported in 21 relevant functional neuroimaging studies. Among these studies, 12 focused on the immediate brain activation and 9 on the long-term activation. Single dataset analysis were employed to identify both immediate and long-term brain activation of acupuncture treatment in IS patients, while contrast and conjunction analysis were utilized to explore distinctions and connections between the two. Results: According to the ALE analysis, immediately after acupuncture treatment, IS patients exhibited an enhanced cluster centered around the right precuneus (PCUN) and a reduced cluster centered on the left middle frontal gyrus (MFG). After long-term acupuncture treatment, IS patients showed an enhanced cluster in the left PCUN, along with two reduced clusters in the right insula (INS) and hippocampus (HIP), respectively. Additionally, in comparison to long-term acupuncture treatment, the right angular gyrus (ANG) demonstrated higher ALE scores immediately after acupuncture, whereas long-term acupuncture resulted in higher scores in the left superior parietal gyrus (SPG). The intersecting cluster activated by both of them was located in the left cuneus (CUN). Conclusion: The findings provide initial insights into both the immediate and long-term brain activation patterns of acupuncture treatment for IS, as well as the intricate interplay between them. Both immediate and long-term acupuncture treatments showed distinct patterns of brain activation, with the left CUN emerging as a crucial regulatory region in their association. [ABSTRACT FROM AUTHOR]

Purpose: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care. Methods: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70). Results: The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor. Conclusion: The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor's location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients. [ABSTRACT FROM AUTHOR]

Background Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. Methods Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6–23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). Results Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. Conclusion Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche. [ABSTRACT FROM AUTHOR]

Purpose: How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents. Methods: Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score. Results: ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05). Conclusion: After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children's hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children. [ABSTRACT FROM AUTHOR]

Neuropsychological studies have demonstrated that meningioma patients frequently exhibit cognitive deficits before surgery and show only limited improvement after surgery. Combining neuropsychological with functional imaging measurements can shed more light on the impact of surgery on cognitive brain function. We aimed to evaluate whether surgery affects cognitive brain activity in such a manner that it may mask possible changes in cognitive functioning measured by neuropsychological tests. Twenty‐three meningioma patients participated in a fMRI measurement using a verbal working memory task as well as three neuropsychological tests focused on working memory, just before and 3 months after surgery. A region of interest based fMRI analysis was used to examine cognitive brain activity at these timepoints within the central executive network and default mode network. Neuropsychological assessment showed impaired cognitive functioning before as well as 3 months after surgery. Neuropsychological test scores, in‐scanner task performance as well as brain activity within the central executive and default mode network were not significantly different between both timepoints. Our results indicate that surgery does not significantly affect cognitive brain activity in meningioma patients the first few months after surgery. Therefore, the lack of cognitive improvement after surgery is not likely the result of compensatory processes in the brain. Cognitive deficits that are already present before surgery appear to be persistent after surgery and a considerable recovery period. Our study shows potential leads that comprehensive cognitive evaluation can be of added value so that cognitive functioning may become a more prominent factor in clinical decision making. [ABSTRACT FROM AUTHOR]

Resting state functional magnetic resonance imaging (R‐fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease‐related variability in intrinsic connectivity networks may influence our interpretation of R‐fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R‐fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network‐based statistics (NBS) and calculations of mean inter‐ and intra‐network connectivity within pre‐defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow‐up) increased intra‐network connectivity, whereas decliners showed exclusively reduced intra‐network and inter‐ (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter‐network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra‐network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter‐network synchrony may support cognitive function in the face of PD‐related network disruptions. [ABSTRACT FROM AUTHOR]

• Transcranial magnetic stimulation is an objective biomarker of upper motor neuron dysfunction in motor neuron disease (MND). • Cortical hyperexcitability is mediated by cortical disinhibition and increased facilitation. • Neuroimaging biomarkers of upper motor neuron dysfunction in MND exhibit utility. Identifying upper motor neuron (UMN) dysfunction is fundamental to the diagnosis and understanding of disease pathogenesis in motor neuron disease (MND). The clinical assessment of UMN dysfunction may be difficult, particularly in the setting of severe muscle weakness. From a physiological perspective, transcranial magnetic stimulation (TMS) techniques provide objective biomarkers of UMN dysfunction in MND and may also be useful to interrogate cortical and network function. Single, paired- and triple pulse TMS techniques have yielded novel diagnostic and prognostic biomarkers in MND, and have provided important pathogenic insights, particularly pertaining to site of disease onset. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) and increased short interval intracortical facilitation, has been associated with the onset of lower motor neuron degeneration, along with patterns of disease spread, development of specific clinical features such as the split hand phenomenon, and may provide an indication about the rate of disease progression. Additionally, reduction of SICI has emerged as a potential diagnostic aid in MND. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction in MND. Separately, sophisticated brain imaging techniques have uncovered novel biomarkers of neurodegeneration that have bene associated with progression. The present review will discuss the utility of TMS and brain neuroimaging derived biomarkers of UMN dysfunction in MND, focusing on recently developed TMS techniques and advanced neuroimaging modalities that interrogate structural and functional integrity of the corticomotoneuronal system, with an emphasis on pathogenic, diagnostic, and prognostic utility. [ABSTRACT FROM AUTHOR]

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

The acquisition of reading modifies areas of the brain associated with vision and with language, in addition to their connections. These changes enable reciprocal translation between orthography and the sounds and meaning of words. Individual variability in the pre-existing cerebral substrate contributes to the range of eventual reading abilities, extending to atypical developmental patterns, including dyslexia and reading-related synaesthesias. The present study is devoted to the little-studied but highly informative ticker-tape synaesthesia, in which speech perception triggers the vivid and irrepressible perception of words in their written form in the mind's eye. We scanned a group of 17 synaesthetes and 17 matched controls with functional MRI, while they listened to spoken sentences, words, numbers or pseudowords (Experiment 1), viewed images and written words (Experiment 2) or were at rest (Experiment 3). First, we found direct correlates of the ticker-tape synaesthesia phenomenon: during speech perception, as ticker-tape synaesthesia was active, synaesthetes showed over-activation of left perisylvian regions supporting phonology and of the occipitotemporal visual word form area, where orthography is represented. Second, we provided support to the hypothesis that ticker-tape synaesthesia results from atypical relationships between spoken and written language processing: the ticker-tape synaesthesia-related regions overlap closely with cortices activated during reading, and the overlap of speech-related and reading-related areas is larger in synaesthetes than in controls. Furthermore, the regions over-activated in ticker-tape synaesthesia overlap with regions under-activated in dyslexia. Third, during the resting state (i.e. in the absence of current ticker-tape synaesthesia), synaesthetes showed increased functional connectivity between left prefrontal and bilateral occipital regions. This pattern might reflect a lowered threshold for conscious access to visual mental contents and might imply a non-specific predisposition to all synaesthesias with a visual content. These data provide a rich and coherent account of ticker-tape synaesthesia as a non-detrimental developmental condition created by the interaction of reading acquisition with an atypical cerebral substrate. [ABSTRACT FROM AUTHOR]

Purpose: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. Methods: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. Results: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. Conclusion: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation. [ABSTRACT FROM AUTHOR]

Background: Recent scientific evidence has challenged the traditional "rest-is-best" approach for concussion management. It is now thought that "exercise-is-medicine" for concussion, owing to dozens of studies which demonstrate that sub-maximal, graded aerobic exercise can reduce symptom burden and time to symptom resolution. However, the primary neuropathology of concussion is altered functional brain activity. To date, no studies have examined the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion. In addition, although exercise is now more widely prescribed following concussion, its cardiopulmonary response is not yet well understood in this population. Our study has two main goals. The first is to understand whether there are exercise-induced resting state functional brain activity differences in children with concussion vs. healthy controls. The second is to profile the physiological response to exercise and understand whether it differs between groups. Methods: We will perform a single-center, controlled, prospective cohort study of pediatric concussion at a large, urban children's hospital and academic center. Children with sport-related concussion (aged 12–17 years) will be recruited within 4-weeks of injury by our clinical study team members. Key inclusion criteria include: medical clearance to exercise, no prior concussion or neurological history, and no implants that would preclude MRI. Age- and sex-matched healthy controls will be required to meet the same inclusion criteria and will be recruited through the community. The study will be performed over two visits separated by 24–48 h. Visit 1 involves exercise testing (following the current clinical standard for concussion) and breath-by-breath gas collection using a metabolic cart. Visit 2 involves two functional MRI (fMRI) scans interspersed by 10-minutes of treadmill walking at an intensity calibrated to Visit 1 findings. To address sub-objectives, all participants will be asked to self-report symptoms daily and wear a waist-worn tri-axial accelerometer for 28-days after Visit 2. Discussion: Our study will advance the growing exercise-concussion field by helping us understand whether exercise impacts outcomes beyond symptoms in pediatric concussion. We will also be able to profile the cardiopulmonary response to exercise, which may allow for further understanding (and eventual optimization) of exercise in concussion management. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Objective: In this work, we propose a novel method for constructing wholebrain spatio-temporal multilayer functional connectivity networks (FCNs) and four innovative rich-club metrics. Methods: Spatio-temporal multilayer FCNs achieve a high-order representation of the spatio-temporal dynamic characteristics of brain networks by combining the sliding time window method with graph theory and hypergraph theory. The four proposed rich-club scales are based on the dynamic changes in rich-club node identity, providing a parameterized description of the topological dynamic characteristics of brain networks from both temporal and spatial perspectives. The proposed method was validated in three independent differential analysis experiments: male-female gender difference analysis, analysis of abnormality in patients with autism spectrum disorders (ASD), and individual difference analysis. Results: The proposed method yielded results consistent with previous relevant studies and revealed some innovative findings. For instance, the dynamic topological characteristics of specific white matter regions effectively reflected individual differences. The increased abnormality in internal functional connectivity within the basal ganglia may be a contributing factor to the occurrence of repetitive or restrictive behaviors in ASD patients. Conclusion: The proposed methodology provides an efficacious approach for constructing whole-brain spatio-temporal multilayer FCNs and conducting analysis of their dynamic topological structures. The dynamic topological characteristics of spatio-temporal multilayer FCNs may offer new insights into physiological variations and pathological abnormalities in neuroscience. [ABSTRACT FROM AUTHOR]

With many viable strategies in the therapeutic pipeline, upcoming clinical trials in hereditary and sporadic degenerative ataxias will benefit from non-invasive MRI biomarkers for patient stratification and the evaluation of therapies. The MRI Biomarkers Working Group of the Ataxia Global Initiative therefore devised guidelines to facilitate harmonized MRI data acquisition in clinical research and trials in ataxias. Recommendations are provided for a basic structural MRI protocol that can be used for clinical care and for an advanced multi-modal MRI protocol relevant for research and trial settings. The advanced protocol consists of modalities with demonstrated utility for tracking brain changes in degenerative ataxias and includes structural MRI, magnetic resonance spectroscopy, diffusion MRI, quantitative susceptibility mapping, and resting-state functional MRI. Acceptable ranges of acquisition parameters are provided to accommodate diverse scanner hardware in research and clinical contexts while maintaining a minimum standard of data quality. Important technical considerations in setting up an advanced multi-modal protocol are outlined, including the order of pulse sequences, and example software packages commonly used for data analysis are provided. Outcome measures most relevant for ataxias are highlighted with use cases from recent ataxia literature. Finally, to facilitate access to the recommendations by the ataxia clinical and research community, examples of datasets collected with the recommended parameters are provided and platform-specific protocols are shared via the Open Science Framework. [ABSTRACT FROM AUTHOR]

In functional MRI (fMRI), effective connectivity analysis aims at inferring the causal influences that brain regions exert on one another. A common method for this type of analysis is structural equation modeling (SEM). We here propose a novel method to test the validity of a given model of structural equation. Given a structural model in the form of a directed graph, the method extracts the set of all constraints of conditional independence induced by the absence of links between pairs of regions in the model and tests for their validity in a Bayesian framework, either individually (constraint by constraint), jointly (e.g., by gathering all constraints associated with a given missing link), or globally (i.e., all constraints associated with the structural model). This approach has two main advantages. First, it only tests what is testable from observational data and does allow for false causal interpretation. Second, it makes it possible to test each constraint (or group of constraints) separately and, therefore, quantify in what measure each constraint (or, e..g., missing link) is respected in the data. We validate our approach using a simulation study and illustrate its potential benefits through the reanalysis of published data. [ABSTRACT FROM AUTHOR]

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD. • There was a negative correlation between the changed WM and plasma BDNF level after SD. • The altered ALFF/fALFF were negatively associated with WM and plasma BDNF level after SD. • The relationship between BDNF and WM may be mediated by altered ALFF/fALFF in brain regions after SD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the feasibility of non-contrast-enhanced functional lung imaging in 2-year-old children after congenital diaphragmatic hernia (CDH) repair. Methods: Fifteen patients after CDH repair were examined using non-contrast-enhanced dynamic magnetic resonance imaging (MRI). For imaging two protocols were used during free-breathing: Protocol A with high temporal resolution and Protocol B with high spatial resolution. The dynamic images were then analysed through a recently developed post-processing method called dynamic mode decomposition (DMD) to obtain ventilation and perfusion maps. The ventilation ratios (VRatio) and perfusion ratios (QRatio) of ipsilateral to contralateral lung were compared to evaluate functional differences. Lastly, DMD MRI-based perfusion results were compared with perfusion parameters obtained using dynamic contrast-enhanced (DCE) MRI to assess agreement between methods. Results: Both imaging protocols successfully generated pulmonary ventilation (V) and perfusion (Q) maps in all patients. Overall, the VRatio and QRatio values were 0.84 ± 0.19 and 0.70 ± 0.24 for Protocol A, and 0.88 ± 0.18 and 0.72 ± 0.23 for Protocol B, indicating reduced ventilation ( p < 0.05 ) and perfusion ( p < 0.01 ) on the ipsilateral side. Moreover, there is a very strong positive correlation ( r > 0.89 , p < 0.01 ) and close agreement between DMD MRI-based perfusion values and DCE MRI-based perfusion parameters. Conclusions: DMD MRI can obtain pulmonary functional information in 2-year-old CDH patients. The results obtained with DMD MRI correlate with DCE MRI, without the need for ionising radiation or exposure to contrast agents. While further studies with larger cohorts are warranted, DMD MRI is a promising option for functional lung imaging in CDH patients. Clinical relevance statement: We demonstrate that pulmonary ventilation and perfusion information can be obtained in 2-year-old patients after CDH repair, without the need for ionising radiation or contrast agents by utilising non-contrast-enhanced MRI acquisitions together with dynamic mode decomposition analysis. Key Points: • Non-contrast-enhanced functional MR imaging is a promising option for functional lung imaging in 2-year-old children after congenital diaphragmatic hernia. • DMD MRI can generate pulmonary ventilation and perfusion maps from free-breathing dynamic acquisitions without the need for ionising radiation or contrast agents. • Lung perfusion parameters obtained with DMD MRI correlate with perfusion parameters obtained using dynamic contrast-enhanced MRI. [ABSTRACT FROM AUTHOR]