Hippocampal Functional Connectivity Changes Research Articles

Hippocampal Resting State Functional Connectivity Associated with Physical Activity in Periadolescent Children.

Periadolescence is a neurodevelopmental period characterized by structural and functional brain changes that are associated with cognitive maturation. The development of the functional connectivity of the hippocampus contributes to cognitive maturation, especially memory processes. Notably, hippocampal development is influenced by lifestyle factors, including physical activity. Physical activity has been associated with individual variability in hippocampal functional connectivity. However, this relationship has not been characterized in a developmental cohort. In this study, we aimed to fill this gap by investigating the relationship between physical activity and the functional connectivity of the hippocampus in a cohort of periadolescents aged 8-13 years (N = 117). The participants completed a physical activity questionnaire, reporting the number of days per week they performed 60 min of physical activity; then, they completed a resting-state functional MRI scan. We observed that greater physical activity was significantly associated with differences in hippocampal functional connectivity in frontal and temporal regions. Greater physical activity was associated with decreased connectivity between the hippocampus and the right superior frontal gyrus and increased connectivity between the hippocampus and the left superior temporal sulcus. Capturing changes in hippocampal functional connectivity during key developmental periods may elucidate how lifestyle factors including physical activity influence brain network connectivity trajectories, cognitive development, and future disease risk.

The decline of verbal memory after stroke is associated with decreased functional connectivity of hippocampal subregions

AbstractBackgroundThe hippocampus plays an important role in learning and integrating events to form episodic memory. Many ischemic stroke survivors experience memory impairments, and some report decline in memory function. We examined changes in functional connectivity (FC) of the hippocampus and its subregions in stroke survivors over 3 years compared to age‐matched stroke‐free healthy controls (HC), and the associations between hippocampal FC and verbal memory performance.MethodParticipants from the Cognition And Neocortical Volume After Stroke Study were analysed at 3‐months, 1‐year and 3‐years post‐stroke. Verbal memory performance at each timepoint was evaluated with delayed recall of the Hopkins Verbal Learning Test‐Revised that was standardized using appropriate age stratified normative data. Evaluable resting‐state functional magnetic resonance imaging sequences were compared with age‐matched healthy controls (see Table 1 for demographics) following pre‐processing. The hippocampus was parcellated into whole hippocampus and four subregions (body, head‐medial, head‐lateral and tail) and bilateral seed‐based FC analyses were conducted for each region using CONN toolbox (V20.b). Longitudinal changes of FC between two timepoints were computed by the direct subtraction.ResultGroups were age‐ and sex‐matched but HC had significantly greater years of education (see Table 1). Greater FC change was seen in stroke survivors between 3‐months to 1‐year in left hippocampal head‐medial (right lateral occipital; p‐FDR = 0.012) with years of education adjusted. Stroke patients displayed significant decline in verbal memory between the 1‐ and 3‐year timepoints. Significantly decreased FC of left hippocampal head‐medial (precuneus; p‐FDR = 0.011) correlated with verbal memory decline between 3‐months and 3 years after adjusting years of education and gender. There was no significant decline or change of verbal memory observed in HC, and the correlated hippocampal FC changes were not present in HC group either.ConclusionChange in left hippocampal subregional FC is different in stroke survivors compared to HC. Subregional hippocampal FC changes correlate with verbal memory decline. Subfield FC analyses may shed new light into mechanisms of post‐stroke memory impairment.

Hippocampal Functional Connectivity and Memory Performance After Exercise Intervention in Older Adults with Mild Cognitive Impairment.

Background:Exercise training (ET) has neuroprotective effects in the hippocampus, a key brain region for memory that is vulnerable to age-related dysfunction.Objective:We investigated the effects of ET on functional connectivity (FC) of the hippocampus in older adults with mild cognitive impairment (MCI) and a cognitively normal (CN) control group. We also assessed whether the ET-induced changes in hippocampal FC (Δhippocampal-FC) are associated with changes in memory task performance (Δmemory performance).Methods:32 older adults (77.0±7.6 years; 16 MCI and 16 CN) participated in the present study. Cardiorespiratory fitness tests, memory tasks (Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LM)), and resting-state fMRI were administered before and after a 12-week walking ET intervention. We utilized a seed-based correlation analysis using the bilateral anterior and posterior hippocampi as priori seed regions of interest. The associations of residualized ET-induced Δhippocampal-FC and Δmemory performance were assessed using linear regression.Results:There were significant improvements in RAVLT Trial 1 and LM test performance after ET across participants. At baseline, MCI, compared to CN, demonstrated significantly lower posterior hippocampal FC. ET was associated with increased hippocampal FC across groups. Greater ET-related anterior and posterior hippocampal FC with right posterior cingulate were associated with improved LM recognition performance in MCI participants.Conclusion:Our findings indicate that hippocampal FC is significantly increased following 12-weeks of ET in older adults and, moreover, suggest that increased hippocampal FC may reflect neural network plasticity associated with ET-related improvements in memory performance in individuals diagnosed with MCI.

The Effect of Early Life Stress on Memory is Mediated by Anterior Hippocampal Network

The experience of early life stress (ELS) is a risk factor for memory dysfunction, but the impact at the neural level is less clear. The aim of this study is to investigate whether healthy people with a higher ELS display more structural and functional changes of hippocampus than people with a lower ELS, and to investigate whether hippocampus changes in turn affects memory. The Childhood Trauma Questionnaire (CTQ) was used to assess ELS in 100 young health participants. They were divided into two groups: “low” CTQ group (limitation of none/minimal ELS) and “high” CTQ group (low to moderate ELS). Verbal memory was assessed by California Verbal Learning Test II and visual memory by Rey-Osterrieth Complex Figure. Resting state fMRI data were acquired and voxel-wise correlation analysis was performed to functionally divide the hippocampus. Gray matter volumes and memory circuits of the anterior and posterior hippocampus were analyzed. We also tested whether changes in hippocampus mediated the relationship between ELS and memory. Compared with participants with a lower ELS, healthy participants with a relatively higher ELS had reduced anterior hippocampal functional connectivity, which positively correlated with visual memory. Among all participants, anterior hippocampal functional connectivity mediated the relationship of ELS on visual memory. These findings suggest that ELS decreased anterior hippocampal-cortical functional connectivity, which, in turn, drives memory decline and highlight a potential pathway in which ELS affects memory by degrading anterior hippocampal functional connectivity changes directly.

Persistent Enhancement of Hippocampal Network Connectivity by Parietal rTMS Is Reproducible.

Wang et al. (2014) found that that five daily sessions of repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) significantly increased functional connectivity (FC) in a network centered on the hippocampus, and caused a correlated increase in memory performance. However, this finding has not been reproduced independently and the requirement for five sessions has not been validated. We aimed to reproduce the imaging results of this experiment, focusing on hippocampal FC changes and using fewer days of rTMS. We measured resting state FC before and after three (N = 9) or four (N = 6) consecutive daily PPC rTMS sessions, using similar delivery parameter settings as Wang et al. (2014). Eight subjects received 3 d of rTMS delivered to the vertex as a control. We employed whole-brain and hypothesis-based statistical approaches to test for hippocampal FC changes. Additionally, we calculated FC in 17 brain networks to determine whether the topographic pattern of FC change was similar between studies. We did not include behavioral testing in this study. PPC, but not vertex, rTMS caused significant changes in hippocampal FC to the same regions as in the previous study. Brain-wide changes in hippocampal FC significantly exceeded changes in global connectedness, indicating that the effect of PPC rTMS was specific to the hippocampal network. Baseline hippocampal FC, measured before receiving stimulation, predicted the degree of rTMS-induced hippocampal FC as in the previous study. These findings reproduce the imaging findings of Wang et al. (2014) and show that FC enhancement can occur after only three to four sessions of PPC rTMS.

Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy.

Seizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery. Twenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters. The results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery. The widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

Postchemotherapy hippocampal functional connectivity patterns in patients with breast cancer: a longitudinal resting state functional MR imaging study

The hippocampus plays a key role in cognitive function and emotion regulation due to its wide connection with the whole brain. This study examined the acute effect of chemotherapy on hippocampal and subfield functional connectivity and neuropsychological status in breast cancer patients (BC). This IRB approved study included 29BC and 25 age matched healthy controls (HCs) who underwent resting state functional magnetic resonance imaging (Rs-fMRI), neuropsychological tests and blood examinations at baseline and one week after completing chemotherapy or in the same time interval. Within-group comparisons and group-by-time interactions analysis of hippocampus- and subregion- based functional connectivity were performed between the two groups. Functional connectivity changes were correlated with changes of blood examination and neuropsychological test scores in the BC group. The BC group had higher depression and anxiety scores, poorer performance on visual mobility, auditory memory and executive function than HCs (p < 0.05), and significantly abnormal estrodiol, total cholesterol and triglycerides (p < 0.05). BC survivors showed significant hippocampal functional connectivity changes mainly in the left insula, temporal lobe (Gaussian Random Field theory correction, P < 0.001) and the left inferior frontal gyrus (P < 0.01). The functional connections from the anterior hippocampus to the left temporal lobe were greater than the posterior hippocampus (P < 0.05). The hippocampus functional connectivity alterations were closely related to changes in depression scores, estrodiol and triglycerides (all p < 0.05). Chemotherapy induced especially anterior hippocampal functional connectivity abnormality, which is related to depression symptom, estrodiol and triglycerides disorders.

Functional Connectivity of the Hippocampus in Temporal Lobe Epilepsy: Feasibility of a Task-Regressed Seed-Based Approach

Resting-state functional connectivity (FC) has revealed marked network dysfunction in patients with temporal lobe epilepsy (TLE) compared to healthy controls. However, the nature and the location of these changes have not been fully elucidated nor confirmed by other methodologies. We assessed the presence of hippocampal FC changes in TLE based on the low frequency residuals of task-related functional magnetic resonance imaging data after the removal of task-related activation [i.e., task-regressed functional connectivity MRI (fcMRI)]. We employed a novel, task-regressed approach to quantify hippocampal FC, and compare hippocampal FC in 17 patients with unilateral TLE (9 left) with 17 healthy controls. Our results suggest widespread FC reductions in the mesial cortex associated with the default mode network (DMN), and some local FC increases in the lateral portions of the right hemisphere. We found more pronounced FC decreases in the left hemisphere than in the right, and these FC decreases were greatest in patients with left TLE. Moreover, the FC reductions observed between the hippocampus and posterior cingulate, inferior parietal, paracentral regions are in agreement with previous resting state studies. Consistent with the existing literature, FC reductions in TLE appear widespread with prominent reductions in the medial portion of the DMN. Our data expand the literature by demonstrating that reductions in FC may be greatest in the left hemisphere and in patients with left TLE. Overall, our findings suggest that task-regressed FC is a viable alternative to resting state and that future studies may extract similar information on network connectivity from already existing datasets.

1440 – Anterior hippocampal connectivity and response to frustration in major depression

Introduction Major depressive disorder (MDD) is associated with low frustration tolerance, which is a risk factor for suicide. Hippocampal structural and functional abnormalities have been documented to play one of the crucial roles in the pathophysiology of depression. Recent studies have revealed functional differentiation of the hippocampus. Thus, activity of the anterior part was shown to be associated with negative affect mediation. Objectives To investigate brain mechanisms of frustration, comparing its impact on anterior hippocampal connectivity in MDD patients and healthy controls (HCs). Methods 14 MDD and 14 HC right-handed subjects were included in the study and underwent comprehensive clinical assessment. MDD was diagnosed during psychiatric interview according to ICD-10 criteria. The Hamilton Depression Rating Scale was additionally used to assess depressive symptoms. The original Stroop test was modified to evoke a state of frustration by administrering impossible task conditions and negative feedback during 10-min functional magnetic resonance scanning session. Psychophysiological interactions were used to analyze left and right anterior hippocampal functional connectivity changes in response to frustration. The resulted Z-maps were adjusted using Z > 2.3 threshold and a (corrected) cluster significance threshold of p = 0.05. Results Increased functional connectivity of the left anterior hippocampus in response to frustration was significantly higher in MDD patients compared to HCs in the pars opercularis of the right prefrontal cortex and bilateral posterior cingulate regions. Conclusion The results revealed that depressed patients demonstrate abnormally increased anterior hippocampal response to frustration, suggesting that hippocampal-neocortical network impairment may contribute to decreased frustration tolerance associated with MDD

Recovery of hippocampal network connectivity correlates with cognitive improvement in mild alzheimer's disease patients treated with donepezil assessed by resting‐state fMRI

To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment. Resting-state functional connectivity magnetic resonance imaging (R-fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age-matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments. After donepezil treatment, neural correlates of cognitive improvement measured by Mini-Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale-cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement. R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.

Structural and Functional Hippocampal Changes in Multiple Sclerosis Patients with Intact Memory Function

To investigate changes in hippocampal functional connectivity and structural measures of hippocampal damage in multiple sclerosis (MS) patients with intact spatial memory, a cognitive domain frequently affected in progressive MS. The study protocol was approved by the institutional ethics review board; all subjects gave written informed consent prior to participation. Twenty-five MS patients with intact spatial memory function were compared with 30 age- and sex-matched controls. Hippocampal volume differences, based on manually drawn masks, were evaluated by using the Student t test. Additionally, focal hippocampal lesions and mean diffusivity were obtained as descriptive measures of structural hippocampal damage. Multiple regression analyses of the resting-state functional magnetic resonance (MR) imaging data were performed for each subject by using hippocampal time series. Between-group analyses were conducted with a mixed-effects model, corrected for multiple comparisons by a cluster defining threshold level of z = 2 and a corrected cluster size significance level of P < .05. Right hippocampal volume was significantly lower in MS patients as compared with controls (P < .01). Left hippocampal volume was also lower in MS patients compared with controls, but not significantly so (P = .09). Resting-state functional connectivity between the hippocampus and its anatomic input or target areas, including the anterior cingulate gyrus, thalamus, and prefrontal cortex, were significantly decreased in MS patients. Decreased hippocampal functional connectivity was more pronounced in a subgroup of MS patients with hippocampal atrophy, although subtle decreases of functional connectivity were also found in patients with normal hippocampal volume. In MS patients, substantial abnormalities of hippocampal functional connectivity are already present before spatial memory function is impaired, especially in those patients with more pronounced hippocampal atrophy. Longitudinal studies should now assess whether these functional connectivity and structural changes may precede memory impairment in MS.