Changes In Functional Connectivity Research Articles

Altered functional connectivity of primary olfactory cortex-hippocampus-frontal cortex in subjective cognitive decline during odor stimulation.

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.

Increased between-network connectivity: A risk factor for tau elevation and disease progression

One of the pathologic hallmarks of Alzheimer’s disease (AD) is neurofibrillary tau tangles. Despite our knowledge that tau typically initiates in the medial temporal lobe (MTL), the mechanisms driving tau to spread beyond MTL remain unclear. Emerging evidence reveals distinct patterns of functional connectivity change during aging and preclinical AD: while connectivity within-network decreases, connectivity between-network increases. Building upon increased between-network connectivity, our study hypothesizes that this increase may play a critical role in facilitating tau spread in early stages. We conducted a longitudinal study over two to three years intervals on a cohort of 46 healthy elderly participants (mean age 64.23 ± 3.15 years, 26 females). Subjects were examined clinically and utilizing advanced imaging techniques that included resting-state functional MRI (rs-fMRI), structural magnetic resonance imaging (MRI), and a second-generation positron emission tomography (PET) tau tracer, 18F-MK6240. Through unsupervised agglomerative clustering and increase in between-network connectivity, we successfully identified individuals at increased risk of future tau elevation and AD progression. Our analysis revealed that individuals with increased between-network connectivity are more likely to experience more future tau deposition, entorhinal cortex thinning, and lower selective reminding test (SRT) delayed scores. Additionally, in the limbic network, we found a strong association between tau progression and increased between-network connectivity, which was mainly driven by beta-amyloid (Aβ) positive participants. These findings provide evidence for the hypothesis that an increase in between-network connectivity predicts future tau deposition and AD progression, also enhancing our understanding of AD pathogenesis in the preclinical stages.

Impact of transcranial electrical stimulation on simultaneous stereoelectroencephalography recordings: A randomized sham-controlled study

ObjectiveClinical exploitation of transcranial electrical stimulation for focal epilepsy treatment lacks quantification of the underlying neurophysiological changes. This study explores the immediate effects of transcranial alternating (tACS) and direct (tDCS) current stimulation on local and network brain activity using simultaneous stereoelectroencephalography (SEEG) recordings. MethodsPatients were randomized for personalized tACS (n = 5) or tDCS (n = 6). Active stimulation (20 min) was preceded by sham stimulation (20 min). Changes in interictal epileptiform discharges (IED), functional connectivity (FC) and power spectral density (PSD) were quantified against baseline. ResultsResults demonstrated variable responses. Spike rate decreased in 2/6 subjects following sham and tDCS, while 2/6 showed an increase. Alpha power and aperiodic PSD components generally increased during and after tDCS but decreased following tACS. FC changes varied among subjects and were detectable even during sham sessions. ConclusionsStrong variability suggests that tES does not have a univocal effect on immediate changes in IED or FC, possibly due to the single session format and challenges in affecting subcortical areas. SignificanceThis is the first study to examine intracranial FC changes during tACS and tDCS, highlighting the importance of sham comparisons and individual variability in tES response, offering valuable insights into its application for epilepsy treatment.

Immediate effect of quadri-pulse stimulation on human brain microstructures and functions

Abstract It remains unclear whether repetitive stimulation of a single brain area immediately alters brain microstructure. Thus, we investigated the immediate changes in human brain microstructures following repetitive extrinsic excitation of the left primary motor cortex (M1) through quadri-pulse stimulation (QPS). Sixteen right-handed healthy adults underwent excitatory (QPS5) and inhibitory (QPS50) QPS. Diffusion magnetic resonance imaging (MRI) and resting-state functional MRI were conducted before and after QPS to detect microstructural and functional changes, respectively. No significant alterations in microstructural indices after QPS5 or QPS50 were observed in the cerebral cortex. The functional connectivity (FC) between the bilateral M1 was significantly decreased after QPS5, while it was not significantly modulated after QPS50. Microstructural changes exhibited no significant correlation with this FC change in any region after QPS5 or QPS50. Although no significant FC change was observed following QPS50, these results may suggest that repetitive stimulation of a single brain area can be insufficient to induce immediate microstructural alterations. This would be supported by demonstrating the lack of microstructural changes after QPS together with changes in cortical excitability of the stimulated region.

Distinct homotopic functional connectivity patterns of the amygdalar sub-regions as biomarkers in major depressive disorder

BackgroundMajor depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs). MethodSixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment. ResultsPatients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = −0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases. LimitationsThe current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined. ConclusionsUsing a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Low arousal threshold is associated with altered functional connectivity of the ascending reticular activating system in patients with obstructive sleep apnea

A low arousal threshold (LAT) is a pathophysiological trait of obstructive sleep apnea (OSA) that may be associated with brainstem ascending reticular activating system-cortical functional connectivity changes. We evaluated resting-state connectivity between the brainstem nuclei and 105 cortical/subcortical regions in OSA patients with or without a LAT and healthy controls. Twenty-five patients with moderate to severe OSA with an apnea–hypopnea index between 20 and 40/hr (15 with and 10 without a LAT) and 15 age- and sex-matched controls were evaluated. Participants underwent functional magnetic resonance imaging after overnight polysomnography. Three brainstem nuclei—the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA)—associated with OSA in our previous study were used as seeds. Functional connectivity values of the two brainstem nuclei (LC and LDTg) significantly differed among the three groups. The connectivity of the LC with the precuneus was stronger in OSA patients than in controls regardless of the concomitant LAT. The connectivity between the LDTg and the posterior cingulate cortex was also stronger in OSA patients regardless of the LAT. Moreover, OSA patients without a LAT showed stronger LDTg-posterior cingulate cortex connectivity than those with a LAT (post hoc p = 0.013), and this connectivity strength was negatively correlated with the minimum oxygen saturation in OSA patients (r = − 0.463, p = 0.023). The LAT in OSA patients was associated with altered LDTg-posterior cingulate cortex connectivity. This result may suggested that cholinergic activity may play a role in the LAT in OSA patients.

Cognitive and Salience Network Connectivity Changes following a Single Season of Repetitive Head Impact Exposure in High School Football.

During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex. Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season. Participants underwent MRI and a cognitive battery (ImPACT) before and shortly after the football season. A control group of noncontact/limited-contact-sport athletes was formed from 2 cohorts: one from the same school and protocol and another from a separate, nearly identical study. Sixty-three football players and 34 control athletes were included in the cognitive performance analysis. Preseason, the control group scored significantly higher on the ImPACT Visual Motor (P = .04) and Reaction Time composites (P = .006). These differences increased postseason (P = .003, P < .001, respectively). Additionally, the control group had significantly higher postseason scores on the Visual Memory composite (P = .001). Compared with controls, football players showed significantly less improvement in the Verbal (P = .04) and Visual Memory composites (P = .01). A significantly greater percentage of contact athletes had lower-than-expected scores on the Verbal Memory (27% versus 6%), Visual Motor (21% versus 3%), and Reaction Time composites (24% versus 6%). Among football players, a higher RWEcp was significantly associated with greater increments in ImPACT Reaction Time (P = .03) and Total Symptom Scores postseason (P = .006). Fifty-seven football players and 13 control athletes were included in the imaging analyses. Postseason, football players showed significant decreases in interhemispheric connectivity of the dorsal anterior cingulate cortex (P = .026) and within-network connectivity of the salience network (P = .018). These decreases in dorsal anterior cingulate cortex interhemispheric connectivity and within-network connectivity of the salience network were significantly correlated with deteriorating ImPACT Total Symptom (P = .03) and Verbal Memory scores (P = .04). Head impact exposure during a single season of high school football is negatively associated with cognitive performance and brain network connectivity. Future studies should further characterize these short-term effects and examine their relationship with long-term sequelae.

Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial.

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study

BackgroundStudies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. MethodsA double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. ResultsThe subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. ConclusionsAfter 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

IBS stress reactivity phenotype is associated with blood transcriptome profiles and microstructural and functional brain changes.

Clinical evidence suggests significant interindividual differences in stress reactivity (SR), but biological mechanisms and therapeutic implications of these differences are poorly understood. We aimed to identify the biological basis of increased SR by investigating associations between a psychometric-based phenotype with blood transcriptomics profiles of increased sympathetic nervous system (SNS) activation and brain imaging phenotypes in irritable bowel syndrome (IBS) participants and healthy controls (HCs). A cross-sectional observational study design, transcriptomics profiling, multimodal brain imaging, and psychosocial assessments were obtained in 291 female and male IBS participants and HCs. Prior to analyses, unsupervised clustering was applied to derive high and low SR subgroups across participants based on two measures of SR. General linear models tested for SR group differences in clinical and biological parameters. Exploratory analyses examined associations between SR group-specific brain alterations and gene expression. The high, compared to low SR group showed greater cyclic AMP response element-binding protein (CREB) gene expression consistent with tonic SNS activity and proinflammatory changes in whole blood. Brain imaging showed neuroplastic changes in the high SR group consistent with an upregulation of ascending arousal systems and sensory processing and integration regions, and functional connectivity changes in the central autonomic network. SR moderated the sex difference in extraintestinal symptoms. The findings support a model of tonically increased SNS activity as a plausible risk factor for increased autonomic reactivity to psychosocial stressors and low grade immune activation in both IBS and HCs, with a greater prevalence in IBS. These findings may have important implications for personalized treatment interventions in IBS.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Frequency modulation increases the specificity of time-resolved connectivity: A resting-state fMRI study.

Representing data using time-resolved networks is valuable for analyzing functional data of the human brain. One commonly used method for constructing time-resolved networks from data is sliding window Pearson correlation (SWPC). One major limitation of SWPC is that it applies a high-pass filter to the activity time series. Therefore, if we select a short window (desirable to estimate rapid changes in connectivity), we will remove important low-frequency information. Here, we propose an approach based on single sideband modulation (SSB) in communication theory. This allows us to select shorter windows to capture rapid changes in the time-resolved functional network connectivity (trFNC). We use simulation and real resting-state functional magnetic resonance imaging (fMRI) data to demonstrate the superior performance of SSB+SWPC compared to SWPC. We also compare the recurring trFNC patterns between individuals with the first episode of psychosis (FEP) and typical controls (TC) and show that FEPs stay more in states that show weaker connectivity across the whole brain. A result exclusive to SSB+SWPC is that TCs stay more in a state with negative connectivity between subcortical and cortical regions. Based on all the results, we argue that SSB+SWPC is more sensitive for capturing temporal variation in trFNC.

Distinct Neural Plasticity Enhancing Visual Perception.

The developed human brain shows remarkable plasticity following perceptual learning, resulting in improved visual sensitivity. However, such improvements commonly require extensive stimuli exposure. Here we show that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural mechanisms relative to standard repetition-based learning. Participants (n = 20, 12 women, 8 men) encoded a visual discrimination task, followed by brief memory reactivations of only five trials each performed on separate days, demonstrating improvements comparable with standard repetition-based learning (n = 20, 12 women, 8 men). Reactivation-induced learning engaged increased bilateral intraparietal sulcus (IPS) activity relative to repetition-based learning. Complementary evidence for differential learning processes was further provided by temporal-parietal resting functional connectivity changes, which correlated with behavioral improvements. The results suggest that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural processes, engaging higher-order control and attentional resources while leading to similar perceptual gains. These unique brain mechanisms underlying improved perceptual learning efficiency may have important implications for daily life and in clinical conditions requiring relearning following brain damage.

Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training.

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections.

Alterations in functional brain connectivity following treatment for restless legs syndrome: The role of symptom improvement in restoring functional connectivity.

The pathophysiology of restless legs syndrome (RLS) remains incompletely understood. Although several studies have investigated the alterations of brain connectivity as one of the pathophysiological mechanisms of RLS, there are only few reports on functional connectivity changes after RLS treatment. Forty-nine patients with newly diagnosed RLS and 50 healthy controls were prospectively enrolled. The patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline, and 39 patients underwent follow-up rs-fMRI, 3 months after treatment with pramipexole or pregabalin. Patients were divided into good or poor medication response groups. Functional brain connectivity was analysed using rs-fMRI and graph theoretical analysis. Significant differences in functional connectivity were observed between the RLS patients and healthy controls. The average path length, clustering coefficient, transitivity, and local efficiency were lower (2.02 vs. 2.30, p < 0.001; 0.45 vs. 0.56, p < 0.001; 3.08 vs. 4.21, p < 0.001; and 0.71 vs. 0.76, p < 0.001, respectively) and the global efficiency was higher (0.53 vs. 0.50, p < 0.001) in patients with RLS than in healthy controls. Differences in functional connectivity at the global level were also observed between post- and pre-treatment RLS patients who showed a good medication response. Transitivity in the post-treatment group was higher than that in the pre-treatment group (3.22 vs. 3.04, p = 0.007). Global efficiency was positively correlated with RLS severity (r = 0.377, p = 0.007). This study demonstrates that RLS is associated with distinct alterations in brain connectivity, which can be partially normalised following symptom management. These findings suggest that therapeutic interventions for RLS modulate brain function, emphasising the importance of symptom-focussed treatment in managing RLS.

Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Conscious but not thinking-Mind-blanks during visuomotor tracking: An fMRI study of endogenous attention lapses.

Attention lapses (ALs) are complete lapses of responsiveness in which performance is briefly but completely disrupted and during which, as opposed to microsleeps, the eyes remain open. Although the phenomenon of ALs has been investigated by behavioural and physiological means, the underlying cause of an AL has largely remained elusive. This study aimed to investigate the underlying physiological substrates of behaviourally identified endogenous ALs during a continuous visuomotor task, primarily to answer the question: Were the ALs during this task due to extreme mind-wandering or mind-blanks? The data from two studies were combined, resulting in data from 40 healthy non-sleep-deprived subjects (20M/20F; mean age 27.1 years, 20-45). Only 17 of the 40 subjects were used in the analysis due to a need for a minimum of two ALs per subject. Subjects performed a random 2-D continuous visuomotor tracking task for 50 and 20 min in Studies 1 and 2, respectively. Tracking performance, eye-video, and functional magnetic resonance imaging (fMRI) were recorded simultaneously. A human expert visually inspected the tracking performance and eye-video recordings to identify and categorise lapses of responsiveness as microsleeps or ALs. Changes in neural activity during 85 ALs (17 subjects) relative to responsive tracking were estimated by whole-brain voxel-wise fMRI and by haemodynamic response (HR) analysis in regions of interest (ROIs) from seven key networks to reveal the neural signature of ALs. Changes in functional connectivity (FC) within and between the key ROIs were also estimated. Networks explored were the default mode network, dorsal attention network, frontoparietal network, sensorimotor network, salience network, visual network, and working memory network. Voxel-wise analysis revealed a significant increase in blood-oxygen-level-dependent activity in the overlapping dorsal anterior cingulate cortex and supplementary motor area region but no significant decreases in activity; the increased activity is considered to represent a recovery-of-responsiveness process following an AL. This increased activity was also seen in the HR of the corresponding ROI. Importantly, HR analysis revealed no trend of increased activity in the posterior cingulate of the default mode network, which has been repeatedly demonstrated to be a strong biomarker of mind-wandering. FC analysis showed decoupling of external attention, which supports the involuntary nature of ALs, in addition to the neural recovery processes. Other findings were a decrease in HR in the frontoparietal network before the onset of ALs, and a decrease in FC between default mode network and working memory network. These findings converge to our conclusion that the ALs observed during our task were involuntary mind-blanks. This is further supported behaviourally by the short duration of the ALs (mean 1.7 s), which is considered too brief to be instances of extreme mind-wandering. This is the first study to demonstrate that at least the majority of complete losses of responsiveness on a continuous visuomotor task are, if not due to microsleeps, due to involuntary mind-blanks.

Alterations in amygdala subregions-Default mode network connectivity after treatment in patients with schizophrenia.

Disrupted connectivity in the default mode network (DMN) during resting-state functional MRI (rs-fMRI) is well-documented in schizophrenia (SCZ). The amygdala, a key component in the neurobiology of SCZ, comprises distinct subregions that may exert varying effects on the disorder. This study aimed to investigate variations in functional connectivity (FC) between distinct amygdala subregions and the DMN in SCZ individuals and explore the effects of treatment on these connections. Fifty-six SCZ patients and 51 healthy controls underwent FC analysis and questionnaire surveys during resting state. The amygdala was selected as the region of interest (ROI) and subdivided into four parts. Changes in FC were examined, and correlations between questionnaire scores and brain activity were explored. Pre-treatment, SCZ patients exhibited reduced FC between the amygdala and DMN compared to HCs. After treatment, significant differences persisted in the right medial amygdala, while other regions did not differ significantly from controls. In addition, PANSS scores positively correlated with FC between the Right Medial Amygdala and the left SMFC (r = .347, p = .009), while RBANS5A scores showed a positive correlation with FC between the Left Lateral Amygdala and the right MTG (rho = -.347, p = .009). The rsFC between the amygdala and the DMN plays a crucial role in the treatment mechanisms of SCZ. This could provide a promising predictive indicator for understanding the neural mechanisms behind treatment and symptomatic improvement.

The White Matter Integrity and Functional Connection Differences of Fornix (Cres)/Stria Terminalis in Individuals with Mild Cognitive Impairment Induced by Occupational Aluminum Exposure.

Long-term aluminum (Al) exposure increases the risk of mild cognitive impairment (MCI). The aim of the present study was to investigate the neural mechanisms of Al-induced MCI. In our study, a total of 52 individuals with occupational Al exposure >10 years were enrolled and divided into two groups: MCI (Al-MCI) and healthy controls (Al-HC). Plasma Al concentrations and Montreal Cognitive Assessment (MoCA) score were collected for all participants. And diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to examine changes of white matter (WM) and functional connectivity (FC). There was a negative correlation between MoCA score and plasma Al concentration. Compared with the Al-HC, fractional anisotropy value for the right fornix (cres)/stria terminalis (FX/ST) was higher in the Al-MCI. Furthermore, there was a difference in FC between participants with and without MCI under Al exposure. We defined the regions with differing FC as a "pathway," specifically the connectivity from the right temporal pole to the right FX/ST, then to the right sagittal stratum, and further to the right anterior cingulate and paracingulate gyri and right inferior frontal gyrus, orbital part. In summary, we believe that the observed differences in WM integrity and FC in the right FX/ST between participants with and without MCI under long-term Al exposure may represent the neural mechanisms underlying MCI induced by Al exposure.