Stronger rsFC Research Articles

Intrinsic brain connectivity alterations despite intact pain inhibition in subjects with neuropathic pain after spinal cord injury: a pilot study

Endogenous pain modulation in humans is frequently investigated with conditioned pain modulation (CPM). Deficient pain inhibition is a proposed mechanism that contributes to neuropathic pain (NP) after spinal cord injury (SCI). Recent studies have combined CPM testing and neuroimaging to reveal neural correlates of CPM efficiency in chronic pain. This study investigated differences in CPM efficiency in relation to resting-state functional connectivity (rsFC) between 12 SCI-NP subjects and 13 age- and sex-matched healthy controls (HC). Twelve and 11 SCI-NP subjects were included in psychophysical and rsFC analyses, respectively. All HC were included in the final analyses. Psychophysical readouts were analysed to determine CPM efficiency within and between cohorts. Group differences of rsFC, in relation to CPM efficiency, were explored with seed-to-voxel rsFC analyses with pain modulatory regions, e.g. ventrolateral periaqueductal gray (vlPAG) and amygdala. Overall, pain inhibition was not deficient in SCI-NP subjects and was greater in those with more intense NP. Greater pain inhibition was associated with weaker rsFC between the vlPAG and amygdala with the visual and frontal cortex, respectively, in SCI-NP subjects but with stronger rsFC in HC. Taken together, SCI-NP subjects present with intact pain inhibition, but can be differentiated from HC by an inverse relationship between CPM efficiency and intrinsic connectivity of supraspinal regions. Future studies with larger cohorts are necessary to consolidate the findings in this study.

The effect of hippocampal radiomic features and functional connectivity on the relationship between hippocampal volume and cognitive function in Alzheimer's disease

Hippocampal volume is associated with cognitive function in Alzheimer's disease (AD). Hippocampal radiomic features and resting-state functional connectivity (rs-FC) are promising biomarkers and correlate with AD pathology. However, few studies have been conducted on how hippocampal biomarkers affect the cognition-structure relationship. Therefore, we aimed to investigate the effects of hippocampal radiomic features and resting-state functional connectivity (rs-FC) on this relationship in AD. We enrolled 70 AD patients and 65 healthy controls (HCs). The FreeSurfer software was used to measure hippocampal volume. We selected hippocampal radiomic features to build a model to distinguish AD patients from HCs and used a seed-based approach to calculate the hippocampal rs-FC. Furthermore, we conducted mediation and moderation analyses to investigate the effect of hippocampal radiomic features and rs-FC on the relationship between hippocampal volume and cognition in AD. The results suggested that hippocampal radiomic features mediated the association between bilateral hippocampal volume and cognition in AD. Additionally, patients with AD showed weaker rs-FC between the bilateral hippocampus and right ventral posterior cingulate cortex and stronger rs-FC between the left hippocampus and left insula than HCs. The rs-FC between the hippocampus and insula moderated the relationship between hippocampal volume and cognition in AD, suggesting that this rs-FC could exacerbate or ameliorate the effects of hippocampal volume on cognition and may be essential in improving cognitive function in AD. Our findings may not only expand existing biological knowledge of the interrelationships among hippocampal biomarkers and cognition but also provide potential targets for treatment strategies for AD.

Central autonomic network alterations in male endurance athletes

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.

Antidepressant Monotherapy and Combination Therapy with Acupuncture in Depressed Patients: A Resting-State Functional Near-Infrared Spectroscopy (fNIRS) Study.

Depression is a common psychiatric illness affecting over 300 million people globally. Acupuncture has been reported to be a safe complementary treatment for depression. This study is aimed to investigate the efficacy and mechanism of combining acupuncture with antidepressants in treating depression compared to the sole use of antidepressants. Seventy depression patients were randomly assigned to the treatment group (n = 50) and control group (n = 20). The treatment group received acupuncture combined antidepressants treatment for 3weeks, while the control group took antidepressants monotherapy for 3weeks. Among the 70 patients, 40 participants (20 control; 20 treatment) were randomized for studying functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) measured by the functional near-infrared spectroscopy. The primary outcome was HAMD-17 and secondary outcomes were PHQ-9, and the relationships of resting-state FC (rsFC) with the depression severity. PHQ-9 and HAMD-17 scores in the treatment group were significantly lower than those in the control group at Week 3 (p = 0.01) with effect sizes of -0.4 and -0.61 respectively. The rsFC in F1, F3, AF3, AF7, FC3, FC5 (left DLPFC, 10-20 system), AF8, and F6 (right DLPFC) in the treatment group had significant temporal correlation (p < 0.05, FDR corrected) in DLPFC compared to the channels in the control group. No significant correlation was found between the changes of rsFC and depression severity. In conclusion, depressed patients receiving acupuncture combined with antidepressants have improvement of depressive symptoms and the stronger rsFC in the DLPFC compared to those using antidepressants alone.

The interaction of child abuse and rs1360780 of the FKBP5 gene is associated with amygdala resting-state functional connectivity in young adults.

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early‐life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion‐processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE‐corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology.

Neural Correlates of Audiovisual Temporal Binding Window in Individuals With Schizotypal and Autistic Traits: Evidence From Resting-State Functional Connectivity.

Temporal proximity is an important clue for multisensory integration. Previous evidence indicates that individuals with autism and schizophrenia are more likely to integrate multisensory inputs over a longer temporal binding window (TBW). However, whether such deficits in audiovisual temporal integration extend to subclinical populations with high schizotypal and autistic traits are unclear. Using audiovisual simultaneity judgment (SJ) tasks for nonspeech and speech stimuli, our results suggested that the width of the audiovisual TBW was not significantly correlated with self-reported schizotypal and autistic traits in a group of young adults. Functional magnetic resonance imaging (fMRI) resting-state activity was also acquired to explore the neural correlates underlying inter-individual variability of TBW width. Across the entire sample, stronger resting-state functional connectivity (rsFC) between the left superior temporal cortex and the left precuneus, and weaker rsFC between the left cerebellum and the right dorsal lateral prefrontal cortex were correlated with a narrower TBW for speech stimuli. Meanwhile, stronger rsFC between the left anterior superior temporal gyrus and the right inferior temporal gyrus was correlated with a wider audiovisual TBW for non-speech stimuli. The TBW-related rsFC was not affected by levels of subclinical traits. In conclusion, this study indicates that audiovisual temporal processing may not be affected by autistic and schizotypal traits and rsFC between brain regions responding to multisensory information and timing may account for the inter-individual difference in TBW width. LAY SUMMARY: Individuals with ASD and schizophrenia are more likely to perceive asynchronous auditory and visual events as occurring simultaneously even if they are well separated in time. We investigated whether similar difficulties in audiovisual temporal processing were present in subclinical populations with high autistic and schizotypal traits. We found that the ability to detect audiovisual asynchrony was not affected by different levels of autistic and schizotypal traits. We also found that connectivity of some brain regions engaging in multisensory and timing tasks might explain an individual's tendency to bind multisensory information within a wide or narrow time window. Autism Res 2021, 14: 668-680. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Shared Characteristics of Intrinsic Connectivity Networks Underlying Interoceptive Awareness and Empathy.

Awareness of internal bodily sensations (interoceptive awareness; IA) and its connection to complex socioemotional abilities like empathy has been postulated, yet the functional neural circuitry they share remains poorly understood. The present fMRI study employs independent component analysis (ICA) to investigate which empathy facet (Cognitive or Affective) shares resting-state functional connectivity (rsFC) and/or BOLD variability (rsBOLD) with IA. Healthy participants viewed an abstract nonsocial movie demonstrated to evoke strong rsFC in brain networks resembling rest (InScapes), and resultant rsFC and rsBOLD data were correlated with self-reported empathy and IA questionnaires. We demonstrate a bidirectional behavioral and neurobiological relationship between empathy and IA, depending on the type of empathy interrogated: Affective empathy and IA share both rsFC and rsBOLD, while Cognitive empathy and IA only share rsBOLD. Specifically, increased rsFC in the right inferior frontal operculum (rIFO) of a larger attention network was associated with increased vicarious experience but decreased awareness of inner body sensations. Furthermore, increased rsBOLD between brain regions of an interoceptive network was related to increased sensitivity to internal sensations along with decreased Affective empathy. Finally, increased rsBOLD between brain regions subserving a mentalizing network related to not only an improved ability to take someone’s perspective, but also a better sense of mind-body interconnectedness. Overall, these findings suggest that the awareness of one’s own internal body changes (IA) is related to the socioemotional ability of feeling and understanding another’s emotional state (empathy) and critically, that this relationship is reflected in the brain’s resting state neuroarchitecture. Methodologically, this work highlights the importance of utilizing rsBOLD as a complementary window alongside rsFC to better understand neurological phenomena. Our results may be beneficial in aiding diagnosis in clinical populations such as autism spectrum disorder (ASD), where participants may be unable to complete tasks or questionnaires due to the severity of their symptoms.

Strength of resting state functional connectivity and local GABA concentrations predict oral reading of real and pseudo-words

Reading is a learned activity that engages multiple cognitive systems. In a cohort of typical and struggling adult readers we show evidence that successful oral reading of real words is related to gamma-amino-butyric acid (GABA) concentration in the higher-order language system, whereas reading of unfamiliar pseudo-words is not related to GABA in this system. We also demonstrate the capability of resting state functional connectivity (rsFC) combined with GABA measures to predict single real word compared to pseudo-word reading performance. Results show that the strength of rsFC between left fusiform gyrus (L-FG) and higher-order language systems predicts oral reading behavior of real words, irrespective of the local concentration of GABA. On the other hand, pseudo-words, which require grapheme-to-phoneme conversion, are not predicted by the connection between L-FG and higher-order language system. This suggests that L-FG may have a multi-functional role: lexical processing of real words and grapheme-to-phoneme processing of pseudo-words. Additionally, rsFC between L-FG, pre-motor, and putamen areas are positively related to the oral reading of both real and pseudo-words, suggesting that text may be converted into a phoneme sequence for speech initiation and production regardless of whether the stimulus is a real word or pseudo-word. In summary, from a systems neuroscience perspective, we show that: (i) strong rsFC between higher order visual, language, and pre-motor areas can predict and differentiate efficient oral reading of real and pseudo-words. (ii) GABA measures, along with rsFC, help to further differentiate the neural pathways for previously learned real words versus unfamiliar pseudo-words.

Migraine in the Young Brain: Adolescents vs. Young Adults.

Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result.

Functional connectivity with cortical depth assessed by resting state fMRI of subregions of S1 in squirrel monkeys.

Whereas resting state blood oxygenation-level dependent (BOLD) functional MRI has been widely used to assess functional connectivity between cortical regions, the laminar specificity of such measures is poorly understood. This study aims to determine: (a) whether the resting state functional connectivity (rsFC) between two functionally related cortical regions varies with cortical depth, (b) the relationship between layer-resolved tactile stimulus-evoked activation pattern and interlayer rsFC pattern between two functionally distinct but related somatosensory areas 3b and 1, and (c) the effects of spatial resolution on rsFC measures. We examined the interlayer rsFC between areas 3b and 1 of squirrel monkeys under anesthesia using tactile stimulus-driven and resting state BOLD acquisitions at submillimeter resolution. Consistent with previous observations in the areas 3b and 1, we detected robust stimulus-evoked BOLD activations with foci were confined mainly to the upper layers (centered at 21% of the cortical depth). By carefully placing seeds in upper, middle, and lower layers of areas 3b and 1, we observed strong rsFC between upper and middle layers of these two areas. The layer-resolved activation patterns in areas 3b and 1 agree with their interlayer rsFC patterns, and are consistent with the known anatomical connections between layers. In summary, using BOLD rsFC pattern, we identified an interlayer interareal microcircuit that shows strong intrinsic functional connections between upper and middle layer areas 3b and 1. RsFC can be used as a robust invasive tool to probe interlayer corticocortical microcircuits.

Modulation of Functional Connectivity in Auditory-Motor Networks in Musicians Compared with Nonmusicians.

Correlation of spontaneous fluctuations at rest between anatomically distinct brain areas are proposed to reflect the profile of individual a priori cognitive biases, coded as synaptic efficacies in cortical networks. Here, we investigate functional connectivity at rest (rs-FC) in musicians and nonmusicians to test for differences in auditory, motor, and audiomotor connectivity. As expected, musicians had stronger rs-FC between the right auditory cortex (AC) and the right ventral premotor cortex than nonmusicians, and this stronger rs-FC was greater in musicians with more years of practice. We also found reduced rs-FC between the motor areas that control both hands in musicians compared with nonmusicians, which was more evident in the musicians whose instrument required bimanual coordination and as a function of hours of practice. Finally, we replicated previous morphometric data to show an increased volume in the right AC in musicians, which was greater in those with earlier musical training, and that this anatomic feature was in turn related to greater rs-FC between auditory and motor systems. These results show that functional coupling within the motor system and between motor and auditory areas is modulated as a function of musical training, suggesting a link between anatomic and functional brain features.

Structural and functional neural correlates of self-reported attachment in healthy adults: evidence for an amygdalar involvement.

The concept of attachment in long-term interpersonal relationships has been linked to relationship outcome and social-emotional health. To date, no relationship between the structural properties of the human amygdala and attachment in romantic relationships (measured through self-reported attachment related anxiety and avoidance) has been described. The aim of the current study was to investigate the relationship between amygdala structure as well as amygdala structural and functional connectivity and attachment anxiety and avoidance. To this end, we collected self-report attachment data on a sample of female young adults. We then examined associations between attachment and mean diffusivity, fractional anisotropy and resting state functional connectivity MRI (rs-FC) of the amygdala and its white matter connections with the prefrontal cortex. We found that lower integrity of the left amygdala was linked with attachment avoidance (e.g., being less comfortable in seeking proximity with others and depending on others) and that greater structural integrity of the uncinate fasciculus was positively associated with avoidance. Lastly, we found that stronger rs-FC between the bilateral amygdala and medial prefrontal regions was linked with greater avoidance. Our findings are compatible with and expand previous results reported by studies that have taken a task-related fMRI approach, furthering our understanding of the neurobiological mechanisms of attachment, and in particular implicating the system formed by amygdala and prefrontal areas in the patterns of behavior that regulate emotional proximity in romantic relationships. These findings have the potential to further our understanding of the affective mechanisms underlying attachment behavior.

COMT Val(158)Met genotypes differentially influence subgenual cingulate functional connectivity in healthy females.

Brain imaging studies have consistently shown subgenual Anterior Cingulate Cortical (sgACC) involvement in emotion processing. catechol-O-methyltransferase (COMT) Val158 and Met158 polymorphisms may influence such emotional brain processes in specific ways. Given that resting-state fMRI (rsfMRI) may increase our understanding on brain functioning, we integrated genetic and rsfMRI data and focused on sgACC functional connections. No studies have yet investigated the influence of the COMT Val158Met polymorphism (rs4680) on sgACC resting-state functional connectivity (rsFC) in healthy individuals. A homogeneous group of 61 Caucasian right-handed healthy female university students, all within the same age range, underwent rsfMRI. Compared to Met158 homozygotes, Val158 allele carriers displayed significantly stronger rsFC between the sgACC and the left parahippocampal gyrus, ventromedial parts of the inferior frontal gyrus (IFG), and the nucleus accumbens (NAc). On the other hand, compared to Val158 homozygotes, we found in Met158 allele carriers stronger sgACC rsFC with the medial frontal gyrus (MFG), more in particular the anterior parts of the medial orbitofrontal cortex. Although we did not use emotional or cognitive tasks, our sgACC rsFC results point to possible distinct differences in emotional and cognitive processes between Val158 and Met158 allele carriers. However, the exact nature of these directions remains to be determined.

Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity

Objectives. Intensified repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) may result in fast clinical responses in treatment resistant depression (TRD). In these kinds of patients, subgenual anterior cingulate cortex (sgACC) functional connectivity (FC) seems to be consistently disturbed. So far, no de novo data on the relationship between sgACC FC changes and clinical efficacy of accelerated rTMS were available. Methods. Twenty unipolar TRD patients, all at least stage III treatment resistant, were recruited in a randomized sham-controlled crossover high-frequency (HF)-rTMS treatment study. Resting-state (rs) functional MRI scans were collected at baseline and at the end of treatment. Results. HF-rTMS responders showed significantly stronger resting-state functional connectivity (rsFC) anti-correlation between the sgACC and parts of the left superior medial prefrontal cortex. After successful treatment an inverted relative strength of the anti-correlations was observed in the perigenual prefrontal cortex (pgPFC). No effects on sgACC rsFC were observed in non-responders. Conclusions. Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.