Reduced Resting-state Functional Connectivity Research Articles

Reduced resting-state functional connectivity of default mode network subsystems in patients with obsessive-compulsive disorder

ObjectivesNeuroimaging studies have reported extensive resting-state functional connectivity (rsFC) abnormalities in the default mode network (DMN) in patients with obsessive-compulsive disorder (OCD), but findings are inconsistent. DMN can be divided into three subsystems: core, dorsal medial prefrontal cortex (dMPFC), and medial temporal lobe (MTL). This study aimed to explore abnormalities in rsFC strength within and between DMN subsystems in OCD patients, and their relationship with clinical symptoms. MethodsThis study recruited 39 OCD patients and 45 healthy controls (HCs). OCD symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). The seed-to-seed method was used to construct rsFC matrix. The rsFC strength within and between the three DMN subsystems were calculated. ResultsCompared to the HC group, the OCD group exhibited reduced rsFC strength within core subsystem (F = 7.799, p = 0.007, Bonferroni corrected p = 0.042). Further, this reduction was also observed in the unmedicated OCD group (n = 19), but not in the medicated OCD group (n = 18). In addition, rsFC strength within core subsystem was negatively correlated with the obsession subscale of YBOCS in the OCD group (r = −0.512, p = 0.004, Bonferroni corrected p = 0.008). Further, this correlation was also significant in the unmedicated OCD group, but not in the medicated OCD group. ConclusionsOur findings suggest that reduced rsFC strength within core subsystem is a feature of OCD patients and may serve as a potential biomarker of obsession severity. Moreover, pharmacological treatments may affect rsFC strength in DMN.

Effects of four-week intranasal oxytocin administration on large-scale brain networks in older adults

Oxytocin (OT) is a crucial modulator of social cognition and behavior. Previous work primarily examined effects of acute intranasal oxytocin administration (IN-OT) in younger males on isolated brain regions. Not well understood are (i) chronic IN-OT effects, (ii) in older adults, (iii) on large-scale brain networks, representative of OT's wider-ranging brain mechanisms. To address these research gaps, 60 generally healthy older adults (mean age = 70.12 years, range = 55–83) were randomly assigned to self-administer either IN-OT or placebo twice daily via nasal spray over four weeks. Chronic IN-OT reduced resting-state functional connectivity (rs-FC) of both the right insula and the left middle cingulate cortex with the salience network but enhanced rs-FC of the left medial prefrontal cortex with the default mode network as well as the left thalamus with the basal ganglia–thalamus network. No significant chronic IN-OT effects were observed for between-network rs-FC. However, chronic IN-OT increased selective rs-FC of the basal ganglia–thalamus network with the salience network and the default mode network, indicative of more specialized, efficient communication between these networks. Directly comparing chronic vs. acute IN-OT, reduced rs-FC of the right insula with the salience network and between the default mode network and the basal ganglia–thalamus network, and greater selective rs-FC of the salience network with the default mode network and the basal ganglia–thalamus network, were more pronounced after chronic than acute IN-OT. Our results delineate the modulatory role of IN-OT on large-scale brain networks among older adults.

Human cerebrospinal fluid monoclonal CASPR2 autoantibodies induce changes in electrophysiology, functional MRI, and behavior in rodent models

Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune encephalitis with a variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction and clinical symptoms are largely unknown. Aiming for analyses from the molecular to the clinical level, we isolated antibody-secreting cells from the cerebrospinal fluid of two patients with CASPR2 encephalitis. From these we cloned four anti-CASPR2 human monoclonal autoantibodies (mAbs) with strong binding to brain and peripheral nerves. All were highly hypermutated and mainly of the IgG4 subclass. Mutagenesis studies determined selective binding to the discoidin domain of CASPR2. Surface plasmon resonance revealed affinities with dissociation constants KD in the pico- to nanomolar range. CASPR2 mAbs interrupted the interaction of CASPR2 with its binding partner contactin 2 in vitro and were internalized after binding to CASPR2-expressing cells. Electrophysiological recordings of rat hippocampal slices after stereotactic injection of CASPR2 mAbs showed characteristic afterpotentials following electrical stimulation. In vivo experiments with intracerebroventricular administration of human CASPR2 mAbs into mice and rats showed EEG-recorded brain hyperexcitability but no spontaneous recurrent seizures. Behavioral assessment of infused mice showed a subtle clinical phenotype, mainly affecting sociability. Mouse brain MRI exhibited markedly reduced resting-state functional connectivity without short-term structural changes. Together, the experimental data support the direct pathogenicity of CASPR2 autoantibodies. The minimally invasive EEG and MRI techniques applied here may serve as novel objective, quantifiable tools for improved animal models, in particular for subtle neuropsychiatric phenotypes or repeated measurements.

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.

Reduced resting-state functional connectivity between insula and inferior frontal gyrus and superior temporal gyrus in hoarding disorder.

Hoarding disorder (HD) is characterized by cognitive control impairments and abnormal brain activity in the insula and anterior cingulate cortex (ACC) during disposal of personal items or certain executive function tasks. However, whether there are any changes in resting-state functional connectivity of the insula and ACC remains unclear. A total of 55 subjects, including 24 patients with HD and 31 healthy controls (HCs), participated in the study. We acquired resting-state functional magnetic resonance imaging data and examined group differences in functional connectivity from the insula and ACC in whole-brain voxels. In patients with HD, functional connectivity was significantly lower between the right insula and right inferior frontal gyrus (IFG) and left superior temporal gyrus (STG) compared to HCs. There was no correlation between these connectivities and HD symptoms. Although the clinical implication is uncertain, our results suggest that patients with HD have resting-state functional alterations between the insula and IFG and STG, corresponding with the results of previous fMRI studies. These findings provide new insight into the neurobiological basis of HD.

Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

Functional Correlates of Intelligence Quotient and Cognitive Abilities Vary According to Maturation in Pediatric MS (P9-3.013)

<h3>Objective:</h3> To test maturation effects on neuropsychological profiles and resting state (RS) functional connectivity (FC) in cognitive and motor networks of pediatric patients with multiple sclerosis (MS). <h3>Background:</h3> Clinical and cognitive features of pediatric MS patients differ from adults. The effect of brain maturation on RS FC and its possible interaction with cognitive features has never been studied. <h3>Design/Methods:</h3> Seventy-six pediatric MS patients underwent a neuropsychological assessment of Wechsler-Intelligence-Scales for Intelligent Quotient (IQ), Semantic/Phonemic Verbal Fluency Test (SVFT/PVFT), Symbol Digit Modalities Test (SDMT), Coding Design (CD) and Block Design (BD) subtests, Trial Making Test (TMT-A/B). In 58 right-handed MS patients and 22 matched healthy controls (HC), RS FC within basal ganglia, executive, language, sensorimotor, and default-mode networks was estimated. Maturation effects were tested by splitting pediatric MS in those below the age of 16 years (B16) (n=46) and those above or equal 16 years (A16) (n=30). <h3>Results:</h3> Most patients (81.6%) achieved IQ scores within or above average values (median IQ=97.5). The highest rate of failure was observed in CD (21.1%), TMT-B (15.8%), TMT-A (10.5%), and SDMT (9.2%). Compared to HC, pediatric MS patients showed reduced RS FC in all networks, mainly involving the caudate nucleus and its connections with cingulate, prefrontal, and sensorimotor cortices. This effect was particularly relevant in younger patients (B16), where reduced basal ganglia, language and executive RS FC was associated with poorer cognitive performances (r range=0.37/0.48), while reduced cingulate RS FC was associated with a lower IQ (r=0.36). In older patients (A16), reduced language and executive RS FC was correlated with lower IQ and CD, BD and PVFT/SVFT scores (r range=0.42–0.67). However, A16 patients also presented increased executive, default-mode and language RS FC <i>vs</i> HC, which was detrimental on performance at the same tests (r range=−0.39/−0.62). <h3>Conclusions:</h3> Maturation significantly impacts on RS FC abnormalities and on their association with cognitive performances. <b>Disclosure:</b> Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Dr. Curatoli has nothing to disclose. Carmen Vizzino has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Monoaminergic network abnormalities: a marker for multiple sclerosis-related fatigue and depression

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on...

Reduced Resting-State Connectivity in Sensory Regions in Juvenile Fibromyalgia

Juvenile fibromyalgia (JFM) is a chronic pain condition affecting predominantly female adolescents. Although JFM pathophysiology has not been addressed, a study found reduced resting-state functional connectivity (rs-FC) in the primary somatosensory system of children with chronic pain. This finding concurs with rs-FC reductions in somatosensory areas described in adults with fibromyalgia. In adults, such rs-FC alterations extended beyond the somatosensory domain and implicated other sensory modalities (3), which may suggest that fibromyalgia patients experience a weakening of sensory integration. Whether this phenomenon replicates in JFM remains to be elucidated. This research aimed to evaluate rs-FC alterations in adolescents with JFM for the first time. We evaluated 37 female adolescents with JFM and 43 matched controls. All participants underwent a resting-state functional magnetic resonance imaging examination. Using an Intrinsic Connectivity Contrast approach, we computed whole-brain, voxel-wise rs-FC and assessed between-group differences via t-tests. Significant clusters were used as seeds of interest in post-hoc seed-to-voxel analyses. The statistical threshold of all analyses was set at family-wise error-corrected p<.05. Compared to controls, JFM patients had decreased whole-brain rs-FC in the primary somatosensory cortex (SI) and the midcingulate cortex, involved in pain processing and response selection. Seed-to-voxel analyses revealed that JFM patients had reduced rs-FC within these regions and between the midcingulate cortex and the bilateral supplementary motor area, posterior insula and parietal operculum (SII), and auditory cortices, thus, areas mediating somatomotor and sensory processing. In contrast, JFM participants showed increased rs-FC between SI and the thalamus, potentially reflecting increased coupling between subcortical and cortical relays of nociceptive processing, and between SI and the ventral anterior insula, involved in affective and visceral processing. Our findings suggest an overall reduction of cortico-cortical integration of sensory signal and an augmented cross-talk between primary sensory and affective-visceral processing regions in adolescents with JFM. This work was funded by NIH/NIAMS Grants R01 AR074795 and P30 AR076316.

Brain Abnormalities in Individuals with a Desire for a Healthy Limb Amputation: Somatosensory, Motoric or Both? A Task-Based fMRI Verdict.

Body integrity dysphoria (BID), a long-lasting desire for the amputation of physically healthy limbs, is associated with reduced fMRI resting-state functional connectivity of somatosensory cortices. Here, we used fMRI to evaluate whether these findings could be replicated and expanded using a task-based paradigm. We measured brain activations during somatosensory stimulation and motor tasks for each of the four limbs in ten individuals with a life-long desire for the amputation of the left leg and fourteen controls. For the left leg, BID individuals had reduced brain activation in the right superior parietal lobule for somatosensory stimulation and in the right paracentral lobule for the motor task, areas where we previously found reduced resting-state functional connectivity. In addition, for somatosensory stimulation only, we found a robust reduction in activation of somatosensory areas SII bilaterally, mostly regardless of the stimulated body part. Areas SII were regions of convergent activations for signals from all four limbs in controls to a significantly greater extent than in subjects with BID. We conclude that BID is associated with altered integration of somatosensory and, to a lesser extent, motor signals, involving limb-specific cortical maps and brain regions where the first integration of body-related signals is achieved through convergence.

Structural Alterations in a Rat Model of Short-Term Conductive Hearing Loss Are Associated With Reduced Resting State Functional Connectivity.

Conductive hearing loss (CHL) results in attenuation of air conducted sound reaching the inner ear. How a change in air conducted sound alters the auditory system resulting in cortical alterations is not well understood. Here, we have assessed structural and functional magnetic resonance imaging (MRI) in an adult (P60) rat model of short-term conductive hearing loss (1 week). Diffusion tensor imaging (DTI) revealed fractional anisotropy (FA) and axial diffusivity alterations after hearing loss that circumscribed the auditory cortex (AC). Tractography found the lateral lemniscus tract leading to the bilateral inferior colliculus (IC) was reduced. For baseline comparison, DTI and tractography alterations were not found for the somatosensory cortex. To determine functional connectivity changes due to hearing loss, seed-based analysis (SBA) and independent component analysis (ICA) were performed. Short term conductive hearing loss altered functional connectivity in the AC and IC, but not the somatosensory cortex. The results present an exploratory neuroimaging assessment of structural alterations coupled to a change in functional connectivity after conductive hearing loss. The results and implications for humans consist of structural-functional brain alterations following short term hearing loss in adults.

Association between long-term exposure to air pollution and ambient noise with altered resting-state brain connectivity in the 1000BRAINS study

Background/Aim: Long-term air pollution (AP) is associated with cognitive impairment and altered brain structure. These changes are also observed during normal aging. Studies in younger children additionally hint at an age-related functional brain reorganization, i.e. reduced resting-state functional connectivity (RSFC) within functional brain networks and increased RSFC between different brain networks. The current study examined the associations between long-term AP and ambient noise (AN) with RSFC reorganization in older adults.Methods: We used data from participants of the German 1000BRAINS study. To measure AP at the participant’s residences for the years 2000-2003, we applied land use regression and spatiotemporal European Air Pollution Dispersion Chemistry Transport modeling. Exposure to AN was modeled as weighted 24-h (LDEN) means and night-time (LNIGHT) means. Between 2011 and 2015, resting-state functional imaging brain scans were acquired. We defined seven resting-state brain networks (RSN): visual, sensorimotor, dorsal- and ventral attention, limbic, frontoparietal and default RSN and evaluated the degree of segregation as the ratio of within-network RSFC and inter-network RSFC. Multiple linear regression models adjusted for age, sex, socioeconomic status and lifestyle variables were used to estimate the relationship of AP and AN with RSFC.Results: The analysis included 583 participants (44.1% female, mean age of 56 years). Overall, clearly decreased segregation patterns were not visible. Weak associations of particular matter (PM2.5), soot and particle number concentration with decreased segregation were observed in the sensorimotor RSN (i.e. 0.088 [95%-Confidence-Interval: -0.170; -0.006] per 1.41 µg/m3 increase in PM2.5). For a 10 dB(A) increase of LDEN and LNIGHT, we observed weak decreases in segregation of the visual RSN.Conclusions: In accordance with major aging theories, higher exposure to AP and AN could possibly lead to an acceleration of age-related functional brain reorganization. To verify these findings, further studies with larger sample size are needed.

The sense of self in the aftermath of trauma: lessons from the default mode network in posttraumatic stress disorder

ABSTRACT Trauma can profoundly affect the sense of self, where both cognitive and somatic disturbances to the sense of self are reported clinically by individuals with posttraumatic stress disorder (PTSD). These disturbances are captured eloquently by clinical accounts, such as, ‘I do not know myself anymore,’ ‘I will never be able to experience normal emotions again,’ and, ‘I feel dead inside.’ Self-related thoughts and experiences are represented neurobiologically by a large-scale, cortical network located along the brain’s mid-line and referred to as the default mode network (DMN). Recruited predominantly during rest in healthy participants, the DMN is also active during self-referential and autobiographical memory processing – processes which, collectively, are thought to provide the foundation for a stable sense of self that persists across time and may be available for conscious access. In participants with PTSD, however, the DMN shows substantially reduced resting-state functional connectivity as compared to healthy individuals, with greater reductions associated with heightened PTSD symptom severity. Critically, individuals with PTSD describe frequently that their traumatic experiences have become intimately linked to their perceived sense of self, a perception which may be mediated, in part, by alterations in the DMN. Accordingly, identification of alterations in the functional connectivity of the DMN during rest, and during subliminal, trauma-related stimulus conditions, has the potential to offer critical insight into the dynamic interplay between trauma- and self-related processing in PTSD. Here, we discuss DMN-related alterations during these conditions, pointing further towards the clinical significance of these findings in relation to past- and present-centred therapies for the treatment of PTSD.

Clinical predictivity of thalamic sub-regional connectivity in clinically isolated syndrome: a 7-year study.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability.

Functional brain connectivity abnormalities and cognitive deficits in neuromyelitis optica spectrum disorder

Background: Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs). Objective: To investigate resting state (RS) functional connectivity (FC) abnormalities within the main cognitive networks in NMOSD patients and their correlation with cognitive performance. Methods: We acquired RS fMRI from 25 NMOSD patients and 30 healthy controls (HC). Patients underwent an extensive neuropsychological evaluation. Between-group RS FC comparisons and correlations with cognitive performance were assessed on the main cognitive RS networks identified by independent component analysis. Results: NMOSD patients showed higher RS FC versus HC in the precuneus of the default mode network (DMN) and right working memory network (WMN), as well as in several frontoparietal regions of the salience network (SN) and bilateral WMNs. Reduced frontal RS FC in NMOSD versus HC was detected in the left WMN. Increased RS FC in the DMN and right WMN was correlated with better cognitive performance, while decreased RS FC in the left WMN was associated with worse cognitive performance. Conclusion: Cognitive-network reorganization occurs in NMOSD. Clinico-imaging correlations suggest an adaptive role of increased RS FC. Conversely, reduced RS FC seems to be a maladaptive mechanism associated with a worse cognitive performance.

Reduced resting-state functional connectivity of the basolateral amygdala to the medial prefrontal cortex in preweaning rats exposed to chronic early-life stress.

Early-life stress (ELS) exposure has long-term consequences for both brain structure and function and impacts cognitive and emotional behavior. The basolateral amygdala (BLA) plays an important role in anxiety and fear conditioning through its extensive anatomical and functional connections, in particular to the medial prefrontal cortex (mPFC). However, how ELS affects amygdala function and connectivity in developing rats is unknown. We used the naturalistic limited bedding/nesting (LB) paradigm to induce chronic stress in the pups between postnatal day (PND) 1-10. Male normal bedding (NB, control) or LB offspring underwent structural and resting-state functional MRI (rs-fMRI) on PND18 and in adulthood (PND74-76). Adult male rats were tested for fear conditioning and extinction behavior prior to scanning. Seed-based functional connectivity maps were generated based on four BLA seeds (left, right, anterior and posterior). At both ages, LB induced different effects on anterior and posterior BLA networks, with significant reductions in rs-fMRI connectivity between the anterior BLA and mPFC in LB compared to NB offspring. BLA connectivity was lateralized by preweaning age, with the right hemisphere displaying more connectivity changes than the left. Weak negative volumetric correlations between the BLA and mPFC were also present, mostly in preweaning LB animals. rs-fMRI connectivity and volumetric changes were associated with enhanced fear behaviors in adult LB offspring. Activation of the LB-exposed neonatal amygdala described previously might accelerate the maturation of BLA-mPFC projections and/or modify the activity of reciprocal connections between these structures, leading to a net reduction in rs-fMRI connectivity and increased fear behavior.

Reduced Resting State Functional Connectivity of the Hippocampi as a Biomarker of Temporal Lobe Epilepsy (P3.283)

Reduced Resting State Functional Connectivity of the Hippocampi as a Biomarker of Temporal Lobe Epilepsy (P3.283)

T231. Reduced Resting-State Functional Connectivity Between Cerebellar Lobules and Cortical Regions in Individuals With Schizophrenia

T231. Reduced Resting-State Functional Connectivity Between Cerebellar Lobules and Cortical Regions in Individuals With Schizophrenia

Cognitive and functional correlates of accelerated long-term forgetting in temporal lobe epilepsy

While we know that hippocampal dysfunction is responsible for the memory deficits that patients with temporal lobe epilepsy exhibit at relatively short study-test delays, the role of this region in accelerated long-term forgetting (ALF) is not yet clear. In the present study, we probed the role of the hippocampus in ALF by directly comparing memory for associations to memory that could be supported by item recognition during a forced choice recognition task over delays ranging from 15-min to 72-h. We additionally examined resting-state functional connectivity between the hippocampus and cortical regions known to be involved in processing these types of stimuli, as well as the relationship between ALF and various clinical variables including structural abnormality in the hippocampus, lateralization of epileptic focus, presence of seizures across the retention period, and standardized composite memory scores. We found evidence of accelerated forgetting for item stimuli (but not associative stimuli) by 6 h post-learning, which became statistically reliable by 72-h. This finding suggests that unlike controls, patients were unable to utilize novelty to reject the incorrect object-scene pair. While none of the examined clinical variables were related to long-term forgetting, reduced resting-state functional connectivity between the affected anterior hippocampus and unaffected lateral temporal cortex predicted forgetting of item stimuli over the 72-h delay. Implications for the role of the hippocampus in accelerated long-term forgetting, and existing theories of systems consolidation in this context are discussed.

Structural connectivity-defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations.

In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005-6018, 2017. © 2017 Wiley Periodicals, Inc.