Longitudinal fMRI Research Articles

Cortical Function in Acute Severe Traumatic Brain Injury and at Recovery: A Longitudinal fMRI Case Study.

Differences in the functional integrity of the brain from acute severe brain injury to subsequent recovery of consciousness have not been well documented. Functional magnetic resonance imaging (fMRI) may elucidate this issue as it allows for the objective measurement of brain function both at rest and in response to stimuli. Here, we report the cortical function of a patient with a severe traumatic brain injury (TBI) in a critically ill state and at subsequent functional recovery 9-months post injury. A series of fMRI paradigms were employed to assess sound and speech perception, command following, and resting state connectivity. The patient retained sound perception and speech perception acutely, as indexed by his fMRI responses. Command following was absent acutely, but was present at recovery. Increases in functional connectivity across multiple resting state networks were observed at recovery. We demonstrate the clinical utility of fMRI in assessing cortical function in a patient with severe TBI. We suggest that hallmarks of the recovery of consciousness are associated with neural activity to higher-order cognitive tasks and increased resting state connectivity.

Spectral dynamic causal modelling of resting-state fMRI: an exploratory study relating effective brain connectivity in the default mode network to genetics.

We conduct an imaging genetics study to explore how effective brain connectivity in the default mode network (DMN) may be related to genetics within the context of Alzheimer's disease and mild cognitive impairment. We develop an analysis of longitudinal resting-state functional magnetic resonance imaging (rs-fMRI) and genetic data obtained from a sample of 111 subjects with a total of 319 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. A Dynamic Causal Model (DCM) is fit to the rs-fMRI scans to estimate effective brain connectivity within the DMN and related to a set of single nucleotide polymorphisms (SNPs) contained in an empirical disease-constrained set which is obtained out-of-sample from 663 ADNI subjects having only genome-wide data. We relate longitudinal effective brain connectivity estimated using spectral DCM to SNPs using both linear mixed effect (LME) models as well as function-on-scalar regression (FSR). In both cases we implement a parametric bootstrap for testing SNP coefficients and make comparisons with p-values obtained from asymptotic null distributions. In both networks at an initial q-value threshold of 0.1 no effects are found. We report on exploratory patterns of associations with relatively high ranks that exhibit stability to the differing assumptions made by both FSR and LME.

Negative Parenting Affects Adolescent Internalizing Symptoms Through Alterations in Amygdala-Prefrontal Circuitry: A Longitudinal Twin Study

BackgroundThe synergic interaction of risk genes and environmental factors has been thought to play a critical role in mediating emotion-related brain circuitry function and dysfunction in depression and anxiety disorders. Little, however, is known regarding neurodevelopmental bases underlying how maternal negative parenting affects emotion-related brain circuitry linking to adolescent internalizing symptoms and whether this neurobehavioral association is heritable during adolescence. MethodsThe effects of maternal parenting on amygdala-based emotional circuitry and internalizing symptoms were examined by using longitudinal functional magnetic resonance imaging among 100 monozygotic twins and 78 dizygotic twins from early adolescence (age 13 years) to mid-adolescence (age 16 years). The mediation effects among variables of interest and their heritability were assessed by structural equation modeling and quantitative genetic analysis, respectively. ResultsExposure to maternal negative parenting was positively predictive of stronger functional connectivity of the amygdala with the ventrolateral prefrontal cortex. This neural pathway mediated the association between negative parenting and adolescent depressive symptoms and exhibited moderate heritability (21%). ConclusionsThese findings highlight that maternal negative parenting in early adolescence is associated with the development of atypical amygdala-prefrontal connectivity in relation to internalizing depressive symptoms in mid-adolescence. Such abnormality of emotion-related brain circuitry is heritable to a moderate degree.

Cortical and subcortical changes following sphenopalatine ganglion blocks in chronic migraine with medication overuse headache: a preliminary longitudinal study

ObjectiveThe purpose of this pilot study was to investigate potential changes in brain morphology (cortical thickness and cortical/subcortical volume) accompanying a series of sphenopalatine ganglion (SPG) blockade treatments in chronic migraine with medication overuse headaches (CMw/MOH).BackgroundLocal anesthetization of the SPG via intranasal application is used for the treatment for multiple types of headache disorders, including CM. Our previous longitudinal fMRI study revealed improved network connectivity after such treatment. However, the impact of SPG blocks on cortical, subcortical gray matter volume and cortical thickness has yet to be assessed.MethodsUsing magnetic resonance imaging (MRI), cortical/subcortical volume were measured in 12 chronic migraine patients before and after a series of 12 SPG blocks administered over a 6-week period (2 per week). The average time between MRI assessments was 6 weeks. Targeted, within-subjects t-tests comparing pre-treatment and post-treatment values in specific apriori brain regions of interest, including the hippocampus, amygdala, basal ganglia, somatosensory cortex, temporal cortex and occipital cortex, were used to estimate the impact of repetitive SPG blocks treatment on brain morphology in CMw/MOH.ResultsCompared to baseline values, the number of moderate/severe headache days per month, HIT-6, PHQ-9 scores and allodynia scores were all significantly improved at the end of treatment. Analysis of MRI data revealed that the volume of the right hippocampus and the right palladium significantly decreased following SPG block treatment, while the volume of the left nucleus accumbens significantly increased following treatment. Cortical thickness in the left temporal pole and left lateral occipito-temporal gyrus significantly decreased following SPG block treatment.ConclusionOur results suggest SPG block treatment is associated with significant symptom improvement as well as significant structural brain changes in regions known to be associated with migraine and chronic pain processing in CMw/MOH.

Alterations Functional Connectivity in Temporal Lobe Epilepsy and Their Relationships With Cognitive Function: A Longitudinal Resting-State fMRI Study.

Background: Cognitive impairments in temporal lobe epilepsy (TLE) patients has been described as a chronically progressive feature of the disease. However, how severe recurrent seizures modify neuronal circuits in the human brain and subsequently degrade cognitive function, remains largely unknown. Here, we aimed to investigate longitudinal alterations by functional magnetic resonance imaging (fMRI) in TLE patients and to assess how those alterations are related to cognitive function performance.Methods: Sixteen TLE patients and 20 normal controls (NCs) were recruited for a study to observe longitudinal alterations in resting-state functional connectivity (FC) and to estimate alertness, orientation, and executive function both at baseline and at a follow-up time ~3 years later.Results: TLE patients, compared with NCs, showed impaired executive function, intrinsic alertness, and phasic alertness and exhibited lengthened reaction time (RT) in the spatial cue and center cue conditions at baseline. The orienting function of TLE patients was declined at follow-up compared to the baseline. Cross-sectional analysis demonstrated that TLE patients displayed significantly greater positive correlation than NCs between the right dorsolateral prefrontal cortex (DLPFC) and the right inferior parietal lobule (IPL) and right superior frontal gyrus (SFG). Furthermore, among TLE patients, the longitudinal study revealed a decrease in correlation between the right DLPFC and the right SFG compared to the baseline. In addition, there was a significant negative correlation between the longitudinal change in FC and the change in orienting function in TLE subjects.Conclusions: Abnormal connectivity between the DLPFC and the SFG suggests the potential of longitudinal resting-state fMRI to delineate regions relevant to cognitive dysfunction for disease progression.

Longitudinal Multimodal fMRI to Investigate Neurovascular Changes in Spontaneously Hypertensive Rats.

Hypertension is an important risk factor for age-related cognitive decline and neuronal pathologies. Studies have shown a correlation between hypertension, disruption in neurovascular coupling and cerebral autoregulation, and cognitive decline. However, the mechanisms behind this are unclear. To further understand this, it is advantageous to study neurovascular coupling as hypertension progresses in a rodent model. Here, we use a longitudinal functional MRI (fMRI) protocol to assess the impact of hypertension on neurovascular coupling in spontaneously hypertensive rats (SHRs). Eight female SHRs were studied at 2, 4, and 6 months of age, as hypertension progressed. Under an IV infusion of propofol, animals underwent fMRI, functional MR spectroscopy, and cerebral blood flow (CBF) quantification to study changes in neurovascular coupling over time. Blood pressure significantly increased at 4 and 6 months (P < .0001). CBF significantly increased at 4 months old (P < .05), in the acute stage of hypertension. The size of the active region decreased significantly at 6 months old (P < .05). Change in glutamate signal during activation, and N-acetyl-aspartate (NAA) signal, remained constant. This study shows that, while cerebral autoregulation is impaired in acute hypertension, the blood oxygenation-level-dependent (BOLD) response remains unaltered until later stages. At this stage, the consistent NAA and glutamate signals show that neuronal death has not occurred, and that neuronal activity is not affected at this stage. This suggests that neuronal activity and viability is not lost until much later, and changes observed here in BOLD activity are due to vascular effects.

Development of Dynamic Functional Architecture during Early Infancy.

Uncovering the moment-to-moment dynamics of functional connectivity (FC) in the human brain during early development is crucial for understanding emerging complex cognitive functions and behaviors. To this end, this paper leveraged a longitudinal resting-state functional magnetic resonance imaging dataset from 51 typically developing infants and, for the first time, thoroughly investigated how the temporal variability of the FC architecture develops at the "global" (entire brain), "mesoscale" (functional system), and "local" (brain region) levels in the first 2 years of age. Our results revealed that, in such a pivotal stage, 1) the whole-brain FC dynamic is linearly increased; 2) the high-order functional systems tend to display increased FC dynamics for both within- and between-network connections, while the primary systems show the opposite trajectories; and 3) many frontal regions have increasing FC dynamics despite large heterogeneity in developmental trajectories and velocities. All these findings indicate that the brain is gradually reconfigured toward a more flexible, dynamic, and adaptive system with globally increasing but locally heterogeneous trajectories in the first 2 postnatal years, explaining why infants have rapidly developing high-order cognitive functions and complex behaviors.

Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

Resting State Functional Connectivity & Parental Bonding in Postpartum Women on Buprenorphine for Opioid Use Disorder

Every day, 130+ people in the U.S. die of opioid use disorder (OUD) overdoses - with OUD prevalence quadrupling from 1999 to 2014. About 100,000 women per year may receive buprenorphine replacement treatment (BT) to prevent withdrawal. Despite concerns from animal models of opioid-induced deficits in maternal behavior and a human Maternal Behavior Neurocircuit model to investigate, little is known about brain and behavior for mothers with OUD and BT. Building on our work on functional connectivity in the maternal brain for depression and parental intervention, we conducted longitudinal functional magnetic resonance imaging (fMRI) in humans to examine resting-state functional connectivity (rs-FC) between the periaqueductal gray (PAG) and hypothalamus + maternal bonding associations.

Developmental maturation of inhibitory control circuitry in a high-risk sample: A longitudinal fMRI study

BackgroundThe goal of this work was to characterize the maturation of inhibitory control brain function from childhood to early adulthood using longitudinal data collected in two cohorts. MethodsFunctional MRI during a go/no-go task was conducted in 290 participants, with 88 % undergoing repeated scanning at 1- to 2-year intervals. One group entered the study at age 7–13 years (n = 117); the other entered at age 18–23 years (n = 173). 33.1 % of the sample had two parents with a substance use disorder (SUD), 43.8 % had one parent with an SUD, and 23.1 % had no parents with an SUD. 1162 scans were completed, covering ages 7–28, with longitudinal data from the cohorts overlapping across ages 16–21. A marginal model with sandwich estimator standard errors was used to characterize voxel-wise age-related changes in hemodynamic response associated with successful inhibitory control. ResultsThere was significant positive linear activation associated with age in the frontal, temporal, parietal, and occipital cortices. No clusters survived thresholding with negative linear, positive or negative quadratic, or positive or negative cubic contrasts. ConclusionsThese findings extend previous cross-sectional and small-scale longitudinal studies that have observed positive linear developmental trajectories of brain function during inhibitory control.

Aberrant static and dynamic functional connectivity of the executive control network in lung cancer patients after chemotherapy: a longitudinal fMRI study

ObjectiveThe purpose of the current study was to investigate chemotherapy-related variations in the intrinsic static and dynamic functional connectivity (sFC and dFC, respectively) of the executive control network (ECN) in lung cancer patients.Materials and methodsIn this study, we evaluated 18 lung cancer patients scanned before and after adjuvant chemotherapy treatment and compared the patients with 21 healthy controls (HCs). All subjects underwent resting-state functional MRI (rs-fMRI). We constructed the sFC and dFC of the bilateral dorsolateral prefrontal cortex (DLPFC) using a sliding-window approach, and the correlations between the changed sFC or dFC and cognitive performance were analyzed.ResultsWhole-brain sFC analysis showed that the lung cancer patients showed significant FC pattern changes in the bilateral DLPFC, mainly in the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus, left superior temporal gyrus, left inferior parietal lobe and the right insula. Furthermore, after chemotherapy, the lung cancer patients showed significantly reduced dFC variability between the right DLPFC and right precuneus compared with HCs. In addition, the decreased dFC between the right DLPFC and left SFG in the lung cancer patients after chemotherapy in state 1 and between the right DLPFC and left insula in the lung cancer patients before chemotherapy in state 2 were negatively correlated with MoCA scores ((r = -0.520, p = 0.039; r = -0.548, p = 0.028, respectively).ConclusionsOur results reveal that dynamic connectivity analysis is more effective and sensitive than methods that assume static brain states for linking brain FC patterns and chemotherapy.

Human Neural Stem Cell Induced Functional Network Stabilization After Cortical Stroke: A Longitudinal Resting-State fMRI Study in Mice.

Most stroke studies dealing with functional deficits and assessing stem cell therapy produce extensive hemispheric damage and can be seen as a model for severe clinical strokes. However, mild strokes have a better prospect for functional recovery. Recently, anatomic and behavioral changes have been reported for distal occlusion of the middle cerebral artery (MCA), generating a well-circumscribed and small cortical lesion, which can thus be proposed as mild to moderate cortical stroke. Using this cortical stroke model of moderate severity in the nude mouse, we have studied the functional networks with resting-state functional magnetic resonance imaging (fMRI) for 12 weeks following stroke induction. Further, human neural stem cells (hNSCs) were implanted adjacent to the ischemic lesion, and the stable graft vitality was monitored with bioluminescence imaging (BLI). Differentiation of the grafted neural stem cells was analyzed by immunohistochemistry and by patch-clamp electrophysiology. Following stroke induction, we found a pronounced and continuously rising hypersynchronicity of the sensorimotor networks including both hemispheres, in contrast to the severe stroke filament model where profound reduction of the functional connectivity had been reported by us earlier. The vitality of grafted neural stem cells remained stable throughout the whole 12 weeks observation period. In the stem cell treated animals, functional connectivity did not show hypersynchronicity but was globally slightly reduced below baseline at 2 weeks post-stroke, normalizing thereafter completely. Our resting-state fMRI (rsfMRI) studies on cortical stroke reveal for the first time a hypersynchronicity of the functional brain networks. This hypersynchronicity appears as a hallmark of mild cortical strokes, in contrast to severe strokes with striatal involvement where exclusively hyposynchronicity has been reported. The effect of the stem cell graft was an early and persistent normalization of the functional sensorimotor networks across the whole brain. These novel functional results may help interpret future outcome investigations after stroke and demonstrate the highly promising potential of stem cell treatment for functional outcome improvement after stroke.

Strengthened Default Mode Network Activation During Delay Discounting in Adolescents with Anorexia Nervosa After Partial Weight Restoration: A Longitudinal fMRI Study.

The capacity of patients with anorexia nervosa (AN) to resist food-based rewards is often assumed to reflect excessive self-control. Previous cross-sectional functional magnetic resonance imaging (fMRI) studies utilizing the delay discounting (DD) paradigm, an index of impulsivity and self-control, suggested altered neural efficiency of decision-making in acutely underweight patients (acAN) and a relative normalization in long-term, weight-recovered individuals with a history of AN (recAN). The current longitudinal study tested for changes in functional magnetic resonance imaging (fMRI) activation during DD associated with intensive weight restoration treatment. A predominately adolescent cohort of 22 female acAN patients (mean age—15.5 years) performed an established DD paradigm during fMRI at the beginning of hospitalization and again after partial weight restoration (≥12% body mass index (BMI) increase). Analyses investigated longitudinal changes in both reward valuation and executive decision-making processes. Additional exploratory analyses included comparisons with data acquired in aged-matched healthy controls (HC) as well as probes of functional connectivity between empirically identified nodes of the “task-positive” frontoparietal control network (FPN) and “task-negative” default-mode network (DMN). While treatment was not associated with changes in behavioral DD parameters or activation, specific to reward processing, deactivation of the DMN during decision-making was significantly less pronounced following partial weight restoration. Strengthened DMN activation during DD might reflect a relative relaxation of cognitive overcontrol or improved self-referential, decision-making. Together, our findings present further evidence that aberrant decision-making in AN might be remediable by treatment and, therefore, might constitute an acute effect rather than a core trait variable of the disorder.

Locating neural transfer effects of n-back training on the central executive: a longitudinal fMRI study

The large number of behavioral studies testing whether working memory training improves performance on an untrained task have yielded inconclusive results. Moreover, some studies have investigated the possible neural changes during the performance of untrained tasks after training. Here, we studied the transfer from n-back training to the Paced Auditory Serial Addition Test (PASAT), two different tasks that use the central executive system to maintain verbal stimuli. Participants completed fMRI sessions at baseline, immediately after one week of training, and at the five-week follow-up. Although behavioral transfer effects were not obtained, training was associated with decreased activation in the anterior dorsolateral prefrontal cortex (DLPFC; BA 9/46) while performing the PASAT that remained stable five weeks later. Consistent with our hypothesis, the changes in the anterior DLFPC largely overlapped with the n-back task fMRI activations. In conclusion, working memory training improves efficiency in brain areas involved in the trained task that may affect untrained tasks, specifically in brain areas responsible for the same cognitive processes.

Frontotemporal degeneration in amyotrophic lateral sclerosis (ALS): a longitudinal MRI one-year study.

Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis. Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year. During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P=.003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points. Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.

Associations between peer attachment and neural correlates of risk processing across adolescence

Adolescence is a period of increased risk-taking behavior where individual differences in risk taking may relate to both adverse and positive experiences with peers. Yet, knowledge on how risk processing develops in the adolescent brain and whether this development is related to peer attachment is limited. In this longitudinal functional magnetic resonance imaging (fMRI) study, we collected data from 167 adolescents (53% male) followed for four annual assessments across ages 13–17 years. At each assessment, participants completed a lottery choice task to assess neural risk processing and reported on their perceived attachment to peers and parents. Behaviorally, risk-preference on the lottery choice task decreased linearly with age. Neural activation during risk processing was consistently found in the insula and dACC across the four assessments and increased linearly from ages 13–17 years. Furthermore, higher peer attachment was related to greater right insula risk processing for males but not for females, even after controlling for parental attachment. The magnitudes of this association did not change with age. Findings demonstrate that neural risk processing shows maturation across adolescence and high peer attachment may be associated with low risk taking by heightening neural sensitivity to potential risks for male adolescents.

Intrinsic differences in insular circuits moderate the negative association betweennicotine dependence andcingulate-striatal connectivity strength.

The development of brain-based biomarkers to assess nicotine dependence severity and treatment efficacy are essential to improve the current marginally effective treatment outcomes. Cross-sectional resting state functional connectivity (rsFC) studies in humans identified a circuit between the dorsal anterior cingulate cortex and the ventral striatum that negatively correlated with increased nicotine dependence severity but was unaffected by acute nicotine administration, suggesting a trait marker of addiction. However, whether this trait circuit dysregulation is predispositional to or resultant from nicotine dependence is unclear. Using a rat model of nicotine dependence with longitudinal fMRI measurements, we assessed the relationship between ACC-striatal rsFC and nicotine dependence severity. Data-driven modularity-based parcellation of the rat medial prefrontal cortex (mPFC) combined with seed-based connectivity analysis with the striatum recapitulated the cingulate-striatum relationship observed in humans. Furthermore, the relationship between cingulate-striatal brain circuits and nicotine dependence severity as indexed by the intensity of precipitated withdrawal, was fully statistically moderated by a predispositional insular-frontal cortical functional circuit. These data suggest that the identified trans-species ACC-striatal circuit relationship with nicotine dependence severity is dysregulated following chronic nicotine administration-induced dependence and may be biased by individual differences in predispositional insula-based striatal-frontal circuits, highlighting the circuit's potential as a biomarker of dependence severity.

The Long-Term Effects of Acupuncture on Hippocampal Functional Connectivity in aMCI with Hippocampal Atrophy: A Randomized Longitudinal fMRI Study

Background. Acupuncture has been used to treat amnestic mild cognitive impairment (aMCI) for many years in China. However, the long-term effects of continuous acupuncture treatment remained unclear. Objective. We aimed to explore the long-term effects of continuous acupuncture treatment on hippocampal functional connectivity (FC) in aMCI. Methods. Fifty healthy control (HC) participants and 28 aMCI patients were recruited for resting-state functional magnetic resonance imaging (fMRI) at baseline. The 28 aMCI patients were then divided into the aMCI acupuncture group, which received acupuncture treatment for 6 months, and the aMCI control group, which received no intervention. All aMCI patients completed the second resting-state fMRI scanning after 6 months of acupuncture treatment. Analysis based on the region of interest and two-way analysis of covariance were both used to explore the long-term effects of acupuncture on cognition change and hippocampal FC in aMCI. Results. Compared to HC, aMCI showed decreased right hippocampal FC with the right inferior/middle temporal gyrus (ITG/MTG), left amygdala, and the right fusiform and increased FC with bilateral caudates at baseline. After acupuncture treatment, the right hippocampal FC with right ITG/MTG enhanced significantly in the aMCI acupuncture group, but continued to decrease in the aMCI control group. Whole brain FC analysis showed enhanced right hippocampal FC with the right ITG and the left MTG in the aMCI acupuncture group relative to the aMCI control group. Furthermore, FC strength of the right hippocampus with right ITG at baseline was negatively correlated with the changes in memory scores of aMCI acupuncture patients. Conclusion. Acupuncture treatment could alleviate the progression of cognitive decline and could enhance hippocampal FC with ITG and MTG in aMCI that may be associated with resilience to resistant against neurodegeneration. The findings provided a better understanding of the long-term effects of acupuncture treatment and confirmed the therapeutic role of acupuncture in aMCI.

Alterations of connectivity patterns in functional brain networks in patients with mild traumatic brain injury: A longitudinal resting-state functional magnetic resonance imaging study.

In the present study, we aimed to characterise changes in functional brain networks in individuals who had sustained uncomplicated mild traumatic brain injury (mTBI). We assessed the progression of these changes into the chronic phase. We also attempted to explore how these changes influenced the severity of post-concussion symptoms as well as the cognitive profile of the patients. A total of 65 patients were prospectively recruited for an advanced magnetic resonance imaging (MRI) scan within 7 days of sustaining mTBI. Of these, 25 were reassessed at 6 months post injury. Differences in functional brain networks were analysed between cases and age- and sex-matched healthy controls using independent component analysis of resting-state functional MRI. Our study revealed reduced functional connectivity in multiple networks, including the anterior default mode network, central executive network, somato-motor and auditory network in patients who had sustained mTBI. A negative correlation between network connectivity and severity of post-concussive symptoms was observed. Follow-up studies performed 6 months after injury revealed an increase in network connectivity, along with an improvement in the severity of post-concussion symptoms. Neurocognitive tests performed at this time point revealed a positive correlation between the functional connectivity and the test scores, along with a persistence of negative correlation between network connectivity and post-concussive symptom severity. Our results suggest that uncomplicated mTBI is associated with specific abnormalities in functional brain networks that evolve over time and may contribute to the severity of post-concussive symptoms and cognitive deficits.

Continuous reorganization of cortical information flow in multiple sclerosis: A longitudinal fMRI effective connectivity study

Effective connectivity (EC) is able to explore causal effects between brain areas and can depict mechanisms that underlie repair and adaptation in chronic brain diseases. Thus, the application of EC techniques in multiple sclerosis (MS) has the potential to determine directionality of neuronal interactions and may provide an imaging biomarker for disease progression. Here, serial longitudinal structural and resting-state fMRI was performed at 12-week intervals over one year in twelve MS patients. Twelve healthy subjects served as controls (HC). Two approaches for EC quantification were used: Causal Bayesian Network (CBN) and Time-resolved Partial Directed Coherence (TPDC). The EC strength was correlated with the Expanded Disability Status Scale (EDSS) and Fatigue Scale for Motor and Cognitive functions (FSMC). Our findings demonstrated a longitudinal increase in EC between specific brain regions, detected in both the CBN and TPDC analysis in MS patients. In particular, EC from the deep grey matter, frontal, prefrontal and temporal regions showed a continuous increase over the study period. No longitudinal changes in EC were attested in HC during the study. Furthermore, we observed an association between clinical performance and EC strength. In particular, the EC increase in fronto-cerebellar connections showed an inverse correlation with the EDSS and FSMC. Our data depict continuous functional reorganization between specific brain regions indicated by increasing EC over time in MS, which is not detectable in HC. In particular, fronto-cerebellar connections, which were closely related to clinical performance, may provide a marker of brain plasticity and functional reserve in MS.