Age‐related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Hippocampal circuit alterations that differentially affect hippocampal subfields are associated with age‐related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A‐P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high‐resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and parahippocampal cortex (PHC) and perirhinal cortex (PRC). This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra‐hippocampal connectivity also reflected an age‐related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior–posterior dysfunction in older adults between hippocampus and PHC was predictive of lure discrimination performance on the Mnemonic similarity task (MST), suggesting a role in memory performance. While age‐related dysfunction within the hippocampal subfields has been well‐documented, these results suggest that the age‐related dysfunction in hippocampal connectivity across the longitudinal axis may also contribute significantly to memory decline in older adults.     

Age‐related differences in functional network segregation in the context of sex and reproductive stage

Age is accompanied by differences in the organization of functional brain networks, which impact behavior in adulthood. Functional networks become less segregated and more integrated with age. However, sex differences in network segregation declines with age are not well‐understood. Further, network segregation in the context of female reproductive stage is relatively understudied, though unmasking such relationships would be informative for elucidating biological mechanisms that contribute to sex‐specific differences in aging. In the current work, we used data from the Cambridge Centre for Ageing and Neuroscience (Cam‐CAN) repository to evaluate differences in resting‐state network segregation as a product of sex and reproductive stage. Reproductive stage was categorized using the Stages of Reproductive Aging Workshop (STRAW+10) criteria. Replicating prior work, we investigated the following functional networks: auditory, cerebellar‐basal ganglia, cingulo‐opercular task control, default mode, dorsal attention, fronto‐parietal task control, salience, sensory somatomotor mouth, sensory somatomotor hand, ventral attention, and visual. First, our results mirror findings from previous work indicating that network segregation is lower with increasing age. Second, when analyzing associations between network segregation and age within each sex separately, we find qualitative differences between females and males. Finally, we report significant effects of reproductive stage on network segregation, though these findings are likely driven by age. Broadly, our results suggest that impacts of sex may be important to evaluate when investigating network segregation differences across adulthood, though further work is needed to determine the unique role of menopause and sex hormones on the organization of functional brain networks within aging females.     

Age‐specificity and generalization of behavior‐associated structural and functional networks and their relevance to behavioral domains

Behavior‐associated structural connectivity (SC) and resting‐state functional connectivity (rsFC) networks undergo various changes in aging. To study these changes, we proposed a continuous dimension where at one end networks generalize well across age groups in terms of behavioral predictions (age‐general) and at the other end, they predict behaviors well in a specific age group but fare poorly in another age group (age‐specific). We examined how age generalizability/specificity of multimodal behavioral associated brain networks varies across behavioral domains and imaging modalities. Prediction models consisting of SC and/or rsFC networks were trained to predict a diverse range of 75 behavioral outcomes in a young adult sample (N = 92). These models were then used to predict behavioral outcomes in unseen young (N = 60) and old (N = 60) subjects. As expected, behavioral prediction models derived from the young age group, produced more accurate predictions in the unseen young than old subjects. These behavioral predictions also differed significantly across behavioral domains, but not imaging modalities. Networks associated with cognitive functions, except for a few mostly relating to semantic knowledge, fell toward the age‐specific end of the spectrum (i.e., poor young‐to‐old generalizability). These findings suggest behavior‐associated brain networks are malleable to different degrees in aging; such malleability is partly determined by the nature of the behavior.     

Reference Ability Neural Network‐selective functional connectivity across the lifespan

Previous studies have demonstrated that four latent variables, or reference abilities (RAs), can account for the majority of age‐related changes in cognition: these being episodic memory, fluid reasoning, speed of processing, and vocabulary. In the current study, we focused on RA‐selective functional connectivity patterns that vary with both age and behavior. We analyzed fMRI data from 287 community‐dwelling adults (20–80 years) on a battery of tests relating to the four RAs (three tests per RA = 12 tests). Functional connectivity values were calculated between a pre‐defined set of 264 ROIs (nodes). Across all participants, we (a) identified connections (edges) that correlated with an RA‐specific indicator variable and, indexing only these edges; (b) performed linear regression analysis per edge, regressing indicator correlations (Model 1) and connectivity values (Model 2) on Age, Behavioral Performance, and the Interaction term; and (c) took the conjunction of significant edges between models. Results revealed a different subset of edges for each RA whose connectivity strength and domain‐selectivity varied with age and behavior. Strikingly, the fluid reasoning RA was particularly vulnerable to the effects of age and displayed the most extensive connectivity and selectivity “footprint” for behavior. These findings indicate that different functional networks are recruited across RA, with fluid reasoning displaying a special status among them.     

Age‐related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

The S and L_G alleles of the serotonin transporter‐linked polymorphic region (5‐HTTLPR) lower serotonin transporter expression. These low‐expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala–prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces depression that emerges in adolescence, whereas decreased serotonin transporter that occurs later in development ameliorates depression. However, no brain imaging research has yet investigated the moderating influence of human development on the link between 5‐HTTLPR and effect‐related brain function. We investigated the age‐related effect of 5‐HTTLPR on amygdala activation and amygdala–prefrontal cortex connectivity using a well‐replicated probe, an emotional face task, in children and adolescents aged 9–19 years. A significant genotype‐by‐age interaction predicted amygdala activation, such that the low‐expressing genotype (S/S and S/L_G) group showed a greater increase in amygdala activation with age compared to the higher expressing (L_A/L_A and S/L_A) group. Additionally, compared to the higher expressing group, the low‐expressing genotype group exhibited decreased connectivity between the right amygdala and ventromedial prefrontal cortex with age. Findings indicate that low‐expressing genotypes may not result in the corticolimbic profile associated with depression risk until later adolescence. Hum Brain Mapp 35:646–658, 2014. © 2012 Wiley‐Periodicals, Inc.     

长期海洛因成瘾者前额叶功能连接的静息态fMRI研究

目的 利用静息态fMRI探讨长期海洛因成瘾者前额叶功能连接的变化情况.方法 13例长期海洛因成瘾者和14例正常者接受静息态fMRI检查,对数据进行相关的预处理后,以前额叶为种子点与全脑每个体素进行相关分析,比较海洛因成瘾组与正常对照组前额叶功能连接的变化情况.结果 以左侧前额叶为种子点进行功能连接分析,海洛因成瘾组左侧前额叶与左侧海马、右侧前扣带回、左侧额中回、右侧额中回、右侧楔前叶功能连接明显低于正常对照组:以右侧前额叶为种子点进行功能连接分析,海洛因成瘾组右侧前额叶与左侧眶额叶、左侧额中回功能连接明显低于正常对照组.结论 长期海洛因成瘾者前额叶与相关脑区的功能连接减弱,前额叶可能参与了海洛因成瘾的维持与戒断后复吸.

Abstract：

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.     

Age‐related differences in practice‐dependent resting‐state functional connectivity related to motor sequence learning

Decreased neural plasticity is observed with healthy ageing in the primary sensorimotor (SM1) cortex thought to participate in motor learning and memory consolidation processes. In the present magnetoencephalography study, the post‐training reorganization of resting‐state functional connectivity (rsFC) and its relation with motor learning and early consolidation in 14 young (19–30 years) and 14 old (66–70 years) healthy participants were investigated. At the behavioral level, participants were trained on a motor sequence learning task then retested 20–30 min later for transient offline gains in performance. Using a sensorimotor seed‐based approach, rsFC relying on beta band power envelope correlation was estimated immediately before and 10 min after the learning episode. Post‐training changes in rsFC (from before to after learning) were correlated with motor learning performance and with the offline improvement in performance within the hour after learning. Young and old participants exhibited differential patterns of sensorimotor‐related rsFC, bearing specific relationships with motor learning and consolidation. Our findings suggest that rsFC changes following learning reflect the offline processing of the new motor skill and contribute to the early memory consolidation within the hour after learning. Furthermore, differences in post‐training changes in rsFC between young and old participants support the hypothesis that ageing modulates the neural circuits underlying the learning of a new motor skill and the early subsequent consolidation stages. Hum Brain Mapp 38:923–937, 2017. © 2016 Wiley Periodicals, Inc.     

Age-related positive emotional reactivity decline associated with the anterior insula based resting-state functional connectivity

Recent studies have suggested that emotional reactivity changes with age, but the neural basis is still unclear. The insula may be critical for the emotional reactivity. The current study examined how ageing affects emotional reactivity using the emotional reactivity task data from a human sample (Cambridge Center for Age and Neuroscience, N = 243, age 18–88 years). The resting-state magnetic resonance measurements from the same sample were used to investigate the potential mechanisms of the insula. In the initial analysis, we conducted partial correlation assessments to examine the associations between emotional reactivity and age, as well as between the gray matter volume (GMV) of the insula and age. Our results revealed that emotional reactivity, especially positive emotional reactivity, decreased with age and that the GMV of the insula was negatively correlated with age. Subsequently, the bilateral insula was divided into six subregions to calculate the whole brain resting-state functional connectivity (rsFC). The mediating effect of the rsFC on age and emotional reactivity was then calculated. The results showed that the rsFC of the left anterior insula (AI) with the right hippocampus, and the rsFCs of the right AI with the striatum and the thalamus were mediated the relationship between positive emotional reactivity and age. Our findings suggest that attenuating emotional reactivity with age may be a strategic adaptation fostering emotional stability and diminishing emotional vulnerability. Meanwhile, the findings implicate a key role for the AI in the changes in positive emotional reactivity with age.     

Stress‐induced reduction in hippocampal volume and connectivity with the ventromedial prefrontal cortex are related to maladaptive responses to stressful military service

Previous studies have shown that people who develop psychopathology such as posttraumatic stress disorder (PTSD) following stress exposure are characterized by reduced hippocampal (HC) volume and impaired HC functional connectivity with the ventromedial prefrontal cortex (vmPFC). Nevertheless, the exact interrelationship between reduced HC volume and HC‐vmPFC connectivity deficits in the context of stress has yet to be established. Furthermore, it is still not clear whether such neural abnormalities are stress induced or precursors for vulnerability. In this study, we combined measurements of MRI, functional MRI (fMRI), and diffusion tensor imaging (DTI) to prospectively study 33 a priori healthy Israeli soldiers both pre‐ and post‐exposure to stress during their military service. Thus, we were able to assess the contributions of structural and functional features of the HC and its connectivity to the onset and progression of maladaptive response to stress (i.e., increased PTSD symptoms post‐exposure). We found that soldiers with decreased HC volume following military service (i.e., post‐exposure) displayed more PTSD‐related symptoms post‐exposure as well as reduced HC‐vmPFC functional and structural connectivity post‐exposure, compared to soldiers with increased HC volume following military service. In contrast, initial smaller HC volume pre‐exposure did not have an effect on any of these factors. Our results therefore suggest that reduction in HC volume and connectivity with the vmPFC together mark a maladaptive response to stressful military service. As stress‐induced HC volume reductions were previously shown to be reversible, these localized biological markers may carry valuable therapeutic potential. Hum Brain Mapp 34:2808–2816, 2013. © 2012 Wiley Periodicals, Inc.     

网络游戏成瘾者伏核功能连接静息态fMRI的研究

目的 利用静息态功能磁共振(fMRI)分析网络游戏成瘾者与伏核存在功能连接的脑区,了解伏核功能异常在网络游戏成瘾发病机制中的作用.方法 网络游戏成瘾者和健康对照组各17例,扫描前上网玩耍自己喜欢的网络游戏,60 min后突然中止网络使用,对被试的网络游戏渴求程度进行心理学测评;休息30 min后进行静息态fMRI扫描,分别选取左、右侧伏核为感兴趣区进行脑功能连接分析,确定与双侧伏核有功能连接的脑区,并将激活程度与网络游戏渴求程度进行相关分析.结果 网络游戏成瘾青少年对网络游戏内容的渴望程度、喜欢程度、再次上网的渴望程度明显高于健康对照组(P＜0.05);网络游戏成瘾组的伏核与前扣带回、中脑、海马功能连接明显高于健康对照组,而与前额叶、颞叶及枕叶功能连接明显低于健康对照组(P＜0.05);网络游戏成瘾者伏核与前额叶、前扣带回、中脑及海马的功能连接程度和网络游戏渴求程度存在相关性(r=0.70、0.76、0.65、0.79,P＜0.05).结论 网络游戏成瘾者伏核功能异常,提示伏核是网络游戏成瘾“奖赏系统”的重要组成部分,伏核功能异常可能参与了网络游戏成瘾的产生与维持.     

A combined diffusion‐weighted and electroencephalography study on age‐related differences in connectivity in the motor network during bimanual performance

We studied the relationship between age‐related differences in inter‐ and intra‐hemispheric structural and functional connectivity in the bilateral motor network. Our focus was on the correlation between connectivity and declined motor performance in older adults. Structural and functional connectivity were estimated using diffusion weighted imaging and resting‐state electro‐encephalography, respectively. A total of 48 young and older healthy participants were measured. In addition, motor performances were assessed using bimanual coordination tasks. To pre‐select regions‐of‐interest (ROIs), a neural model was adopted that accounts for intra‐hemispheric functional connectivity between dorsal premotor area (PMd) and primary motor cortex (M1) and inter‐hemispheric connections between left and right M1 (M1_L and M1_R). Functional connectivity was determined via the weighted phase‐lag index (wPLI) in the source‐reconstructed beta activity during rest. We quantified structural connectivity using kurtosis anisotropy (KA) values of tracts derived from diffusion tensor‐based fiber tractography between the aforementioned areas. In the group of older adults, wPLI values between M1_L–M1_R were negatively associated with the quality of bimanual motor performance. The additional association between wPLI values of PMd_L––M1_L and PMd_R–M1_L supports that functional connectivity with the left hemisphere mediated (bimanual) motor control in older adults. The correlational analysis between the selected structural and functional connections revealed a strong association between wPLI values in the left intra‐hemispheric PMd_L–M1_L pathway and KA values in M1_L–M1_R and PMd_R–M1_L pathways in the group of older adults. This suggests that weaker structural connections in older adults correlate with stronger functional connectivity and, hence, poorer motor performance.     

Age‐related changes in amygdala–frontal connectivity during emotional face processing from childhood into young adulthood

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age‐related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7–25 years. We found age‐related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age‐related change (shifting from positive to negative correlation) in amygdala–anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom‐up amygdala excitatory signaling to ACC/mPFC in children and later development of top‐down inhibitory control of ACC/mPFC over amygdala in adults. Age‐related changes in amygdala–ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala–ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat‐specific processing. Hum Brain Mapp 37:1684–1695, 2016. © 2016 Wiley Periodicals, Inc .     

Human immunodeficiency virus‐related decreases in corpus callosal integrity and corresponding increases in functional connectivity

People living with human immunodeficiency virus (PLWH) often have neurocognitive impairment. However, findings on HIV‐related differences in brain network function underlying these impairments are inconsistent. One principle frequently absent from these reports is that brain function is largely emergent from brain structure. PLWH commonly have degraded white matter; we hypothesized that functional communities connected by degraded white matter tracts would show abnormal functional connectivity. We measured white matter integrity in 69 PLWH and 67 controls using fractional anisotropy (FA) in 24 intracerebral white matter tracts. Then, among tracts with degraded FA, we identified gray matter regions connected to these tracts and measured their functional connectivity during rest. Finally, we identified cognitive impairment related to these structural and functional connectivity systems. We found HIV‐related decreased FA in the corpus callosum body (CCb), which coordinates activity between the left and right hemispheres, and corresponding increases in functional connectivity. Finally, we found that individuals with impaired cognitive functioning have lower CCb FA and higher CCb functional connectivity. This result clarifies the functional relevance of the corpus callosum in HIV and provides a framework in which abnormal brain function can be understood in the context of abnormal brain structure, which may both contribute to cognitive impairment.     

Comparison of the personality and other psychological factors of students with internet addiction who do and do not have associated social dysfunction

Background

There is ongoing controversy about whether or not internet addiction should be considered a non-substance behavioral addiction (like gambling disorder) and, if so, what diagnostic criteria should be used to define the condition. Current criteria for internet addiction give equal diagnostic weight to the physiological symptoms and the social consequences of internet addiction.

Aim

Assess the psychological correlates of social dysfunction among individuals with internet addiction.

Methods

A total of 133 students who sought treatment at the Guangji Psychiatric Hospital from July 2011 to December 2013 for psychological problems related to excessive internet use and who currently met Young criteria for internet addiction were identified; 31 of the 38 students who meet rigorous criteria for concurrent internet-related social dysfunction and a random sample of 44 of the 95 students without concurrent social dysfunction completed a battery of psychosocial measures: seven supplementary scales of the Minnesota Multiphasic Personality Inventory (MMPI), the Egna Minnen av Barndoms Uppfostran perceived parenting scale, the Perceived Social Support Scale, the Trait Coping Style Questionnaire, and the Symptom Checklist 90.

Results

Compared to persons with internet addiction without accompanying social dysfunction, those with social dysfunction had higher levels of interpersonal sensitivity, hostility, and paranoia; lower levels of social responsibility, anxiety, self-control, and family social support; and they were more likely to employ negative coping strategies. There were however, no differences in perceived parenting styles between the two groups.

Conclusions

A relatively small proportion of individuals who meet the physiological markers of internet addiction simultaneously report significant internet-related social dysfunction. There are several psychosocial measures that distinguish persons with internet addiction who do or do not have concurrent social dysfunction. Further research is needed to determine whether or not these are two distinct subtypes of internet addiction and whether or not persons with internet addiction without concurrent social dysfunction should be classified as suffering from a ‘mental disorder’.     

Frequency‐specific neuromodulation of local and distant connectivity in aging and episodic memory function

A growing literature has focused on the brain's ability to augment processing in local regions by recruiting distant communities of neurons in response to neural decline or insult. In particular, both younger and older adult populations recruit bilateral prefrontal cortex (PFC) as a means of compensating for increasing neural effort to maintain successful cognitive function. However, it remains unclear how local changes in neural activity affect the recruitment of this adaptive mechanism. To address this problem, we combined graph theoretical measures from functional MRI with diffusion weighted imaging and repetitive transcranial magnetic stimulation (rTMS) to resolve a central hypothesis: how do aged brains flexibly adapt to local changes in cortical activity? Specifically, we applied neuromodulation to increase or decrease local activity in a cortical region supporting successful memory encoding (left dorsolateral PFC or DLPFC) using 5 or 1 Hz rTMS, respectively. We then assessed a region's local within‐module degree, or the distributed between‐module degree (BMD) between distant cortical communities. We predicted that (1) local stimulation‐related deficits may be counteracted by boosting BMD between bilateral PFC, and that this effect should be (2) positively correlated with structural connectivity. Both predictions were confirmed; 5 Hz rTMS increased local success‐related activity and local increases in PFC connectivity, while 1 Hz rTMS decreases local activity and triggered a more distributed pattern of bilateral PFC connectivity to compensate for this local inhibitory effect. These results provide an integrated, causal explanation for the network interactions associated with successful memory encoding in older adults. Hum Brain Mapp 38:5987–6004, 2017 . © 2017 Wiley Periodicals, Inc.     

Brain functional connectivity alterations associated with neuropsychological performance 6–9 months following SARS‐CoV‐2 infection

Neuropsychological deficits and brain damage following SARS‐CoV‐2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6–9 months following SARS‐CoV‐2 infection. SARS‐CoV‐2 infection causes long‐term memory and executive dysfunctions, related to large‐scale functional brain connectivity alterations.     

Freezing of gait in Parkinson's disease is associated with altered functional brain connectivity

BackgroundPatients with Parkinson's disease (PD) may develop several gait disturbances during the course of illness and Freezing of gait (FOG) is one of them. Several neuroimaging studies have been conducted to identify the neural correlates of FOG but results have not been uniform. Resting state functional MRI (rs-fMRI) is relatively less explored in PD patients with FOG. This study aims to compare the whole brain resting state connectivity of PD patients with and without FOG using rs-fMRI.Methodsrs-fMRI was obtained for 28 PD patients (15 with and 13 patients without FOG) who were matched for various demographic and clinical characteristics. Seed to voxel analysis was performed at whole brain level and compared between the two groups.ResultsWhen compared to patients without FOG, the patients with FOG had reduced functional connectivity across multiple seeds. Major finding was reduced inter-hemispheric connectivity of left parietal opercular cortex with multiple regions of the brain primarily involving the primary somatosensory and auditory areas, which also negatively correlated with the FOGQ scores.ConclusionOur findings suggest that alterations in the resting state functional connectivity of the opercular parietal cortex may be one of the substrates of FOG. Reduced interhemispheric connectivity probably is the reason for impairment of control and coordination in bilateral leg movements while walking.