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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.

Objective Methods Results Significance 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.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.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.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]

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]

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: 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: 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]

ObjectiveMethodsResultsConclusionTo 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).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.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.Parcel-guided rTMS is safe and may be effective in reducing PCS symptoms following TBI and should incite further controlled studies. [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]

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.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

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.

Abstract Background Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects. Methods This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10–20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg. Discussion This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders. Trial registration Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

Abstract Background Identification of cortical loci for lower limb movements for stroke rehabilitation is crucial for better rehabilitation outcomes via noninvasive brain stimulation by targeting the fine-grained cortical loci of the movements. However, identification of the cortical loci for lower limb movements using functional MRI (fMRI) is challenging due to head motion and difficulty in isolating different types of movement. Therefore, we developed a custom-made MR-compatible footplate and leg cushion to identify the cortical loci for lower limb movements and conducted multivariate analysis on the fMRI data. We evaluated the validity of the identified loci using both fMRI and behavioral data, obtained from healthy participants as well as individuals after stroke. Methods We recruited 33 healthy participants who performed four different lower limb movements (ankle dorsiflexion, ankle rotation, knee extension, and toe flexion) using our custom-built equipment while fMRI data were acquired. A subgroup of these participants (Dataset 1; n = 21) was used to identify the cortical loci associated with each lower limb movement in the paracentral lobule (PCL) using multivoxel pattern analysis and representational similarity analysis. The identified cortical loci were then evaluated using the remaining healthy participants (Dataset 2; n = 11), for whom the laterality index (LI) was calculated for each lower limb movement using the cortical loci identified for the left and right lower limbs. In addition, we acquired a dataset from 15 individuals with chronic stroke for regression analysis using the LI and the Fugl–Meyer Assessment (FMA) scale. Results The cortical loci associated with the lower limb movements were hierarchically organized in the medial wall of the PCL following the cortical homunculus. The LI was clearer using the identified cortical loci than using the PCL. The healthy participants (mean ± standard deviation: 0.12 ± 0.30; range: – 0.63 to 0.91) exhibited a higher contralateral LI than the individuals after stroke (0.07 ± 0.47; – 0.83 to 0.97). The corresponding LI scores for individuals after stroke showed a significant positive correlation with the FMA scale for paretic side movement in ankle dorsiflexion (R2 = 0.33, p = 0.025) and toe flexion (R2 = 0.37, p = 0.016). Conclusions The cortical loci associated with lower limb movements in the PCL identified in healthy participants were validated using independent groups of healthy participants and individuals after stroke. Our findings suggest that these cortical loci may be beneficial for the neurorehabilitation of lower limb movement in individuals after stroke, such as in developing effective rehabilitation interventions guided by the LI scores obtained for neuronal activations calculated from the identified cortical loci across the paretic and non-paretic sides of the brain.

In-Seon Lee,1 Da-Eun Yoon,1 Seoyoung Lee,2 Jae-Hwan Kang,3,4 Younbyoung Chae,1 Hi-Joon Park,1 Junsuk Kim5 1College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Department of Physics and Computational Radiology, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway; 3Digital Health Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; 5School of Information Convergence, Kwangwoon University, Seoul, Republic of KoreaCorrespondence: Junsuk Kim, School of Information Convergence, Kwangwoon University, 20 Kwangwoon-ro, Seoul, 01897, Republic of Korea, Tel +82-2-940-8477, Email junsuk.kim@kw.ac.kr Hi-Joon Park, College of Korean Medicine, Kyung Hee University, 26 Kyunghee-daero, Seoul, 02447, Republic of Korea, Tel +82-2-961-9435, Email acufind@khu.ac.krPurpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not.Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models.Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level.Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.Keywords: Atopic Dermatitis, deep learning, functional MRI, biomarkers, personalized medicine

Peter A Pahapill,1 Elsa V Arocho-Quinones,1 Guangyu Chen,2 Brad Swearingen,3 Carissa W Tomas,3 Kevin M Koch,3 Andrew Scott Nencka3 1Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; 2Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, USA; 3Center for Neuroimaging, Medical College of Wisconsin, Milwaukee, WI, USACorrespondence: Peter A Pahapill, Tel +1-414-805-5400, Fax +1-414-955-0115, Email ppahapill@mcw.eduBackground: Chronic low back pain (cLBP) has been associated with alterations in brain functional connectivity (FC) but based upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CN FC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain).Methods: In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CN analysis was performed on 7 brain networks and compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores.Results: CN FC involving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FC for intermittent pain but negatively correlated for constant pain.Conclusion: This is the first report of 1) altered CN FC involving emotion/reward brain circuitry in 2) a homogeneous population of cLBP patients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBP patients as compared to controls and were characteristic for each pain phenotype. These data support fcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different pain phenotypes.Keywords: spinal cord stimulation, persistent spinal pain syndrome, functional MRI, chronic pain

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]

Neuroimaging studies have helped to illuminate the effects of opioids on the central nervous system (CNS) under various conditions, including acute opioid administration; treatment of acute, subacute, and chronic pain; and opioid use disorder (OUD). Exogenous opioids impart their effects via brain systems involved in pain, affect, cognition, and reward/value processes. Opioid effects on these brain processes may be similar across chronic pain and OUD treatment, although neuroimaging evidence on opioid effects in chronic pain remains relatively limited. Opioid-imparted CNS alterations, as assessed via neuroimaging, appear to relate to the dose and duration of opioid use, and these alterations may persist for several months after cessation of opioid use. Novel treatments for OUD and opioid cessation/tapering should focus on ameliorating opioid-induced CNS consequences. Evidence of central nervous system (CNS) exogenous opioid effects in humans has been primarily gained through neuroimaging of three participant populations: individuals after acute opioid administration, those with opioid use disorder (OUD), and those with chronic pain receiving opioid therapy. In both the brain and spinal cord, opioids alter processes of pain, cognition, and reward. Opioid-related CNS effects may persist and accumulate with longer opioid use duration. Meanwhile, opioid-induced benefits versus risks to brain health remain unclear. This review article highlights recent accumulating evidence for how exogenous opioids impact the CNS in humans. While investigation of CNS opioid effects has remained largely disparate across contexts of opioid acute administration, OUD, and chronic pain opioid therapy, integration across these contexts may enable advancement toward effective interventions. [ABSTRACT FROM AUTHOR]

Introduction: Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients. Methods: Four language templates (A–D) based on anatomy, task‐based fMRI, resting‐state fMRI, and meta‐analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by the template (positive inclusion fraction, [PIF]), the fraction of activations within the template but that did not belong to PLAs (false inclusion fraction, [FIF]), and their Dice similarity coefficient (DSC) with PLA activations were calculated. Results: For anterior PLAs, Template A had the greatest PIF (median, 0.95), whereas Template D had both the lowest FIF (median, 0.074), and the highest DSC (median, 0.30), which were all significant compared to other templates. For posterior PLAs, Templates B and D had similar PIF (median, 0.91 and 0.90, respectively) and DSC (both medians, 0.059), which were all significantly higher than that of Template C. Templates B and C had significantly lower FIF (median, 0.061 and 0.054, respectively) compared to Template D. Conclusion: This study demonstrated significant differences between language templates in their inclusiveness of and spatial agreement with the PLAs detected in the presurgical fMRI of the patient cohort. These findings may help guide the selection of language templates tailored to their applications in clinical fMRI studies. [ABSTRACT FROM AUTHOR]

Background. Dyslexia is a neurological disorder that affects an individual’s language processing abilities. Early care and intervention can help dyslexic individuals succeed academically and socially. Recent developments in deep learning (DL) approaches motivate researchers to build dyslexia detection models (DDMs). DL approaches facilitate the integration of multi-modality data. However, there are few multimodality-based DDMs. Methods. In this study, the authors built a DL-based DDM using multi-modality data. A squeeze and excitation (SE) integrated MobileNet V3 model, self-attention mechanisms (SA) based EfficientNet B7 model, and early stopping and SA-based Bi-directional long short-term memory (Bi-LSTM) models were developed to extract features from magnetic resonance imaging (MRI), functional MRI, and electroencephalography (EEG) data. In addition, the authors fine-tuned the LightGBM model using the Hyperband optimization technique to detect dyslexia using the extracted features. Three datasets containing FMRI, MRI, and EEG data were used to evaluate the performance of the proposed DDM. Results. The findings supported the significance of the proposed DDM in detecting dyslexia with limited computational resources. The proposed model outperformed the existing DDMs by producing an optimal accuracy of 98.9%, 98.6%, and 98.8% for the FMRI, MRI, and EEG datasets, respectively. Healthcare centers and educational institutions can benefit from the proposed model to identify dyslexia in the initial stages. The interpretability of the proposed model can be improved by integrating vision transformers-based feature extraction. [ABSTRACT FROM AUTHOR]

Over the past decade, a growing body of research in adults has emphasized the role of the cerebellum in social and emotional cognition. This has been further supported by findings of delayed social and emotional development in toddlers with cerebellar injury during the fetal and newborn periods. However, the contributions of the cerebellum to social-emotional development in typically developing newborns are unclear. To bridge this gap in knowledge, we used multimodal MRI to investigate associations between cerebellar structure and function in 88 healthy neonates (mean ± sd of postmenstrual age, = 42.00 ± 1.91 weeks) and social-emotional development at 18-months assessed using the Infant-Toddler Social-Emotional Assessment (ITSEA) (mean age on ITSEA: 18.32 ± 1.19 months old). We found that cerebellar volume was not associated with ITSEA domain scores at 18 months. We further demonstrated cerebellar functional gradient (FGR) defined using principal component analysis (PCA) was associated with Externalizing domain (linear regression model, falsediscovery-rate-adjusted p = 0.013). This cluster (FGR7) included the left dentate, right VI, left Vermis VIIIb, and right V lobules. Finally, we demonstrated that either structural or functional features of the cerebellum reliably predicted scores on the Externalizing and Internalizing domains (correlation between actual and predicted scores: for structural, Fisher's z = 0.48 ± 0.01 for Internalizing, p = 0.01; for functional, Fisher's z = 0.45 ± 0.01 for Externalizing, p = 0.02; with permutation test). Collectively, our findings suggest that the cerebellum plays an important role in social-emotional development during the critical early stages of life. [ABSTRACT FROM AUTHOR]

Introduction: Cerebrospinal fluid (CSF) flow is involved in brain waste clearance and may be impaired in neurodegenerative diseases such as Parkinson's disease. This study aims to investigate the relationship between the CSF pulsation and the development of dementia in Parkinson's disease (PD) patients using EPI-based fMRI. Methods: We measured CSF pulsation in the 4th ventricle of 17 healthy controls and 35 PD patients using a novel CSF pulsation index termed "CSFpulse" based on echo-planar imaging (EPI)-based fMRI. The PD patients were classified into a PD with dementia high-risk group (PDD-H, n = 19) and a low risk group (PDD-L, n = 16), depending on their development of dementia within 5 years after initial brain imaging. The size of the 4th ventricle was measured using intensity-based thresholding. Results: We found that CSF pulsation was significantly higher in PD patients than in healthy controls, and that PD patients with high risk of dementia (PDD-H) had the highest CSF pulsation. We also observed an enlargement of the 4th ventricle in PD patients compared to healthy controls. Conclusion: Our results suggest that CSF pulsation may be a potential biomarker for PD progression and cognitive decline, and that EPI-based fMRI can be a useful tool for studying CSF flow and brain function in PD. [ABSTRACT FROM AUTHOR]

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome. [ABSTRACT FROM AUTHOR]

Mental Time Travel (MTT) allows us to remember past events and imagine future ones. According to previous literature, the Temporal Distance of events affects MTT: our ability to order events worsens for close, compared to far, events. However, those studies established distances a-priori, albeit the way we perceive events' temporal distance may subjectively differ from their objective distance. Thus, in the current study, we aimed to investigate the effects of Perceived Temporal Distance (PTD) on the MTT ability and the brain areas mediating this process. Thirty-three healthy volunteers took part in an fMRI MTT task. Participants were asked to project themselves into the past, present, or future, and to judge a series of events as relative-past or relative-future, in relation to the adopted time location. Outside the scanner, participants provided PTD estimates for each stimulus of the MTT task. Participants' performance and functional activity were analyzed as a function of these estimations. At the behavioural level, PTD predicts the modulation of the performance for relative-past and relative-future. Bilateral angular gyrus, retrosplenial cortex, temporo-parietal region and medial, middle and superior frontal gyri mediate the PTD effect. In addition to these areas, the closer the relative-future events are perceived, the higher the involvement of left parahippocampal and lingual gyri and right cerebellum. Thus, perceived proximity of events activates frontal and posterior parietal areas, which therefore might mediate the processing of PTD in the cognitive spatial representation of time. Future proximity also activates cerebellum and medial temporal areas, known to be involved in imaginative and constructive cognitive functions. [ABSTRACT FROM AUTHOR]

Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied. Fifty eight preadolescent children (aged 9–10 years) with BED and 68 age, body mass index and developmentally matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development Study. We investigated task-evoked blood-oxygen-level-dependent response during functional magnetic resonance imaging, as participants completed the monetary incentive delay task and the stop signal task. We indexed group differences in regions of interest in the reward (orbitofrontal cortex, nucleus accumbens) and inhibitory control (dorsolateral prefrontal cortex, anterior cingulate cortex). No significant group differences emerged during tasks of inhibitory control among children with BED and children without BED. Similarly, no significant group differences emerged during the anticipation or receipt of reward among children with BED and children without BED. Preadolescent children with BED do not demonstrate abnormal neural activity in prominent nodes of reward or inhibitory control circuitry during tasks of inhibitory control, reward anticipation, and reward receipt, relative to children without BED who also had a similar body mass index. [ABSTRACT FROM AUTHOR]

Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N < 50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions. Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD (N = 664 in activation analyses, N = 474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N = 290 in activation analyses, N = 214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces. Compared to controls, LMDD was associated with increased activations in left amygdala (P FWE = 0.031 , k E = 4) and left DLPFC (P FWE = 0.002 , k E = 33), increased mean bilateral amygdala activation (β = 0.0715 , P = 0.0314), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time. Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time. LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of 'bottom-up' limbic-prefrontal effective connectivity in depression. • Lifetime MDD is related to higher amygdala and DLPFC activations to fearful faces. • There is increased inhibition from amygdala to DLPFC when viewing fearful faces in LMDD. • Changes are not attributed to acute MDD severity or antidepressant medication status. • Results help substantially reduce ambiguity in the previous depression literature. [ABSTRACT FROM AUTHOR]

Background: Identification of cortical loci for lower limb movements for stroke rehabilitation is crucial for better rehabilitation outcomes via noninvasive brain stimulation by targeting the fine-grained cortical loci of the movements. However, identification of the cortical loci for lower limb movements using functional MRI (fMRI) is challenging due to head motion and difficulty in isolating different types of movement. Therefore, we developed a custom-made MR-compatible footplate and leg cushion to identify the cortical loci for lower limb movements and conducted multivariate analysis on the fMRI data. We evaluated the validity of the identified loci using both fMRI and behavioral data, obtained from healthy participants as well as individuals after stroke. Methods: We recruited 33 healthy participants who performed four different lower limb movements (ankle dorsiflexion, ankle rotation, knee extension, and toe flexion) using our custom-built equipment while fMRI data were acquired. A subgroup of these participants (Dataset 1; n = 21) was used to identify the cortical loci associated with each lower limb movement in the paracentral lobule (PCL) using multivoxel pattern analysis and representational similarity analysis. The identified cortical loci were then evaluated using the remaining healthy participants (Dataset 2; n = 11), for whom the laterality index (LI) was calculated for each lower limb movement using the cortical loci identified for the left and right lower limbs. In addition, we acquired a dataset from 15 individuals with chronic stroke for regression analysis using the LI and the Fugl–Meyer Assessment (FMA) scale. Results: The cortical loci associated with the lower limb movements were hierarchically organized in the medial wall of the PCL following the cortical homunculus. The LI was clearer using the identified cortical loci than using the PCL. The healthy participants (mean ± standard deviation: 0.12 ± 0.30; range: – 0.63 to 0.91) exhibited a higher contralateral LI than the individuals after stroke (0.07 ± 0.47; – 0.83 to 0.97). The corresponding LI scores for individuals after stroke showed a significant positive correlation with the FMA scale for paretic side movement in ankle dorsiflexion (R2 = 0.33, p = 0.025) and toe flexion (R2 = 0.37, p = 0.016). Conclusions: The cortical loci associated with lower limb movements in the PCL identified in healthy participants were validated using independent groups of healthy participants and individuals after stroke. Our findings suggest that these cortical loci may be beneficial for the neurorehabilitation of lower limb movement in individuals after stroke, such as in developing effective rehabilitation interventions guided by the LI scores obtained for neuronal activations calculated from the identified cortical loci across the paretic and non-paretic sides of the brain. [ABSTRACT FROM AUTHOR]

Introduction: Approximately one in six people will experience an episode of major depressive disorder (MDD) in their lifetime. Effective treatment is hindered by subjective clinical decision-making and a lack of objective prognostic biomarkers. Functional MRI (fMRI) could provide such an objective measure but the majority of MDD studies has focused on static approaches, disregarding the rapidly changing nature of the brain. In this study, we aim to predict depression severity changes at 3 and 6 months using dynamic fMRI features. Methods: For our research, we acquired a longitudinal dataset of 32 MDD patients with fMRI scans acquired at baseline and clinical follow-ups 3 and 6 months later. Several measures were derived from an emotion face-matching fMRI dataset: activity in brain regions, static and dynamic functional connectivity between functional brain networks (FBNs) and two measures from a wavelet coherence analysis approach. All fMRI features were evaluated independently, with and without demographic and clinical parameters. Patients were divided into two classes based on changes in depression severity at both follow-ups. Results: The number of coherence clusters (nCC) between FBNs, reflecting the total number of interactions (either synchronous, anti-synchronous or causal), resulted in the highest predictive performance. The nCC-based classifier achieved 87.5% and 77.4% accuracy for the 3- and 6-months change in severity, respectively. Furthermore, regression analyses supported the potential of nCC for predicting depression severity on a continuous scale. The posterior default mode network (DMN), dorsal attention network (DAN) and two visual networks were the most important networks in the optimal nCC models. Reduced nCC was associated with a poorer depression course, suggesting deficits in sustained attention to and coping with emotion-related faces. An ensemble of classifiers with demographic, clinical and lead coherence features, a measure of dynamic causality, resulted in a 3-months clinical outcome prediction accuracy of 81.2%. Discussion: The dynamic wavelet features demonstrated high accuracy in predicting individual depression severity change. Features describing brain dynamics could enhance understanding of depression and support clinical decision-making. Further studies are required to evaluate their robustness and replicability in larger cohorts. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex‐based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex‐based symptom differences. This study aimed to summarize sex‐based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex‐based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level‐dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low‐frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low‐frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex‐based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex‐based differences in the clinical presentation and course of the disorder. [ABSTRACT FROM AUTHOR]

Blood‐level oxygenation‐dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most common modality to study functional connectivity in the human brain. Most research to date has focused on connectivity between pairs of brain regions. However, attention has recently turned towards connectivity involving more than two regions, that is, higher‐order connectivity. It is not yet clear how higher‐order connectivity can best be quantified. The measures that are currently in use cannot distinguish between pairwise (i.e., second‐order) and higher‐order connectivity. We show that genuine higher‐order connectivity can be quantified by using multivariate cumulants. We explore the use of multivariate cumulants for quantifying higher‐order connectivity and the performance of block bootstrapping for statistical inference. In particular, we formulate a generative model for fMRI signals exhibiting higher‐order connectivity and use it to assess bias, standard errors, and detection probabilities. Application to resting‐state fMRI data from the Human Connectome Project demonstrates that spontaneous fMRI signals are organized into higher‐order networks that are distinct from second‐order resting‐state networks. Application to a clinical cohort of patients with multiple sclerosis further demonstrates that cumulants can be used to classify disease groups and explain behavioral variability. Hence, we present a novel framework to reliably estimate genuine higher‐order connectivity in fMRI data which can be used for constructing hyperedges, and finally, which can readily be applied to fMRI data from populations with neuropsychiatric disease or cognitive neuroscientific experiments. [ABSTRACT FROM AUTHOR]