Changes In Intrinsic Functional Connectivity Research Articles

Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study.

This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.

Resting state functional brain connectivity in child and adolescent psychiatry: where are we now?

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

Subthalamic nucleus–language network connectivity predicts dopaminergic modulation of speech function in Parkinson’s disease

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.

A Method to Estimate Longitudinal Change Patterns in Functional Network Connectivity of the Developing Brain Relevant to Psychiatric Problems, Cognition, and Age.

Aim: To develop an approach to evaluate multiple overlapping brain functional change patterns (FCPs) in functional network connectivity (FNC) and apply to study developmental changes in brain function. Introduction: FNC, the network analog of functional connectivity (FC), is commonly used to capture the intrinsic functional relationships among brain networks. Ongoing research on longitudinal changes of intrinsic FC across whole-brain functional networks has proven useful for characterizing age-related changes, but to date, there has been little focus on capturing multivariate patterns of FNC change with brain development. Methods: In this article, we introduce a novel approach to evaluate multiple overlapping FCPs by utilizing FNC matrices. We computed FNC matrices from the large-scale Adolescent Brain Cognitive Development data using fully automated spatially constrained independent component analysis (ICA). We next evaluated changes in these patterns for a 2-year period using a second-level ICA on the FNC change maps. Results: Our proposed approach reveals several highly structured (modular) FCPs and significant results including strong brain FC between visual and sensorimotor domains that increase with age. We also find several FCPs that are associated with longitudinal changes of psychiatric problems, cognition, and age in the developing brain. Interestingly, FCP cross-covariation, reflecting coupling between maximally independent FCPs, also shows significant differences between upper and lower quartile loadings for longitudinal changes in age, psychiatric problems, and cognition scores, as well as baseline age in the developing brain. FCP patterns and results were also found to be highly reliable based on analysis of data collected in a separate scan session. Conclusion: In sum, our results show evidence of consistent multivariate patterns of functional change in emerging adolescents and the proposed approach provides a useful and general tool to evaluate covarying patterns of whole-brain functional changes in longitudinal data. Impact statement In this article, we introduce a novel approach utilizing functional network connectivity (FNC) matrices to estimate multiple overlapping brain functional change patterns (FCPs). The findings demonstrate several well-structured FCPs that exhibit significant changes for a 2-year period, particularly in the functional connectivity between the visual and sensorimotor domains. In addition, we discover several FCPs that are associated with psychopathology, cognition, and age. Finally, our proposed approach for studying age-related FCPs represents a pioneering method that provides a valuable tool for assessing interconnected patterns of whole-brain functional changes in longitudinal data and may be useful to study change over time with applicability to many other areas, including the study of longitudinal changes within diagnostic groups, treatment effects, aging effects, and more.

Compounding Vulnerability in the Neurocircuitry of Addiction: Longitudinal Functional Connectivity Changes in Alcohol Use Disorder.

The addiction neurocircuitry model describes the role of several brain circuits (drug reward, negative emotionality and craving/executive control) in alcohol use and subsequent development of alcohol use disorder (AUD). Human studies examining longitudinal change using resting-state functional magnetic resonance imaging (rs-fMRI) are needed to understand how functional changes to these circuits are caused by or contribute to continued AUD. In order to characterize how intrinsic functional connectivity changes with sustained AUD, we analyzed rs-fMRI data from individuals with (n = 18; treatment seeking and non-treatment seeking) and without (n = 21) AUD collected on multiple visits as part of various research studies at the NIAAA intramural program from 2012 to 2020. Results of the seed correlation analysis showed that individuals with AUD had an increase in functional connectivity over time between emotionality and craving neurocircuits, and a decrease between executive control and reward networks. Post hoc investigations of AUD severity and alcohol consumption between scans revealed an additive effect of these AUD features in many of the circuits, such that more alcohol consumption or more severe AUD was associated with more pronounced changes to synchronicity. These findings suggest an increased concordance of networks underlying emotionality and compulsions toward drinking while also a reduction in control network connectivity, consistent with the addiction neurocircuitry model. Further, they suggest a compounding effect of continued heavy drinking on these vulnerabilities in neurocircuitry. More longitudinal research is necessary to understand the trajectories of individuals with AUD not adequately represented in this study, as well as whether this can inform effective harm reduction strategies.

Age-Related Intrinsic Functional Connectivity Changes of Locus Coeruleus from Childhood to Older Adults.

The locus coeruleus is critical for selective information processing by modulating the brain’s connectivity configuration. Increasingly, studies have suggested that LC controls sensory inputs at the sensory gating stage. Furthermore, accumulating evidence has shown that young children and older adults are more prone to distraction and filter out irrelevant information less efficiently, possibly due to the unoptimized LC connectivity. However, the LC connectivity pattern across the life span is not fully examined yet, hampering our ability to understand the relationship between LC development and the distractibility. In this study, we examined the intrinsic network connectivity of the LC using a public fMRI dataset with wide-range age samples. Based on LC-seed functional connectivity maps, we examined the age-related variation in the LC connectivity with a quadratic model. The analyses revealed two connectivity patterns explicitly. The sensory-related brain regions showed a positive quadratic age effect (u-shape), and the frontal regions for the cognitive control showed a negative quadratic age effect (inverted u-shape). Our results imply that such age-related distractibility is possibly due to the impaired sensory gating by the LC and the insufficient top-down controls by the frontal regions. We discuss the underlying neural mechanisms and limitations of our study.

Intrinsic functional connectivity changes in drug-naïve Parkinson's disease patients with mild cognitive impairment

Mild cognitive impairment (MCI) is a common nonmotor symptom in Parkinson's disease (PD) and it is considered a risk factor for developing dementia. Using resting-state functional MRI, we investigated intrinsic brain networks connectivity correlates of MCI in a cohort of drug-naïve patients with PD.

Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder.

Autism spectrum disorder has long been conceptualized as a disorder of "atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions)." However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6-30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

Intrinsic functional connectivity in families genetically enriched for social anxiety disorder - an endophenotype study.

BackgroundSocial anxiety disorder (SAD) is a serious psychiatric condition with a high prevalence, and a typical onset during childhood/adolescence. The condition runs in families, but it is largely unknown which neurobiological characteristics transfer this genetic vulnerability (‘endophenotypes’). Using data from the Leiden Family Lab study on SAD, including two generations of families genetically enriched for SAD, we investigated whether social anxiety (SA) co-segregated with changes in intrinsic functional connectivity (iFC), and examined heritability.MethodsFunctional MRI data were acquired during resting-state in 109 individuals (56 males; mean age: 31·5, range 9·2-61·5 years). FSL's tool MELODIC was used to perform independent component analysis. Six networks of interest (default mode, dorsal attention, executive control, frontoparietal, limbic and salience) were identified at the group-level and used to generate subject-specific spatial maps. Voxel-wise regression models, with SA-level as predictor and voxel-wise iFC as candidate endophenotypes, were performed to investigate the association with SA, within masks of the networks of interest. Subsequently, heritability was estimated.FindingsSA co-segregated with iFC within the dorsal attention network (positive association in left middle frontal gyrus and right postcentral gyrus) and frontoparietal network (positive association within left middle temporal gyrus) (cluster-forming-threshold z>2·3, cluster-corrected extent-threshold p<0·05). Furthermore, iFC of multiple voxels within these clusters was at least moderately heritable.InterpretationThese findings provide initial evidence for increased iFC as candidate endophenotype of SAD, particularly within networks involved in attention. These changes might underlie attentional biases commonly present in SAD.FundingLeiden University Research Profile ‘Health, Prevention and the Human Lifecycle’.

Impaired intrinsic functional connectivity among medial temporal lobe and sub-regions related to memory deficits in intracranial dural arteriovenous fistula.

The functional changes concerning memory deficits in dural arteriovenous fistula (dAVF) brain are inadequately understood. This study aimed to understand the functional connectivity alterations of brain regions widely affirmed for explicit and implicit memory functions in dAVF patients (DP) and look into the frequency effects of the altered functional networks. Resting-state functional magnetic resonance imaging (rsfMRI) analysis was done in the memory-associated regions of 30 DP and 30 healthy controls (HC). Frequency decomposition was used to determine potential frequency-dependent functional connectivity changes. They underwent neuropsychological tests and were correlated with changes in memory networks compared with HC. The results showed weaker functional connectivity among the medial temporal lobe and sub-regions in DP suggestive of dysfunction of explicit and implicit memory functions, which corroborated with the positive correlation between memory scores and hippocampal-parahippocampal connectivity of DP, along with a significant group difference of lower memory and cognitive performance in DP assessed by neuropsychological tests. A frequency-dependent study of the altered rsFC revealed lower functional connectivity strength and impaired neural coupling manifested at some sub-band frequencies indicative of disturbed cortical rhythm in DP. This pilot study gives insights into significant intrinsic functional connectivity changes in the memory regions of the dAVF brain. The results may have clinical implications in the choice of interventional management of dAVF and can impact clinical decision making for realizable prevention of progressive memory impairment and irreversible brain damage in such patients.

Altered Regional Cerebral Blood Flow and Brain Function Across the Alzheimer's Disease Spectrum: A Potential Biomarker.

Objective: To investigate variation in the characteristics of regional cerebral blood flow (rCBF), brain activity, and intrinsic functional connectivity (FC) across the Alzheimer's disease spectrum (ADS).Methods: The study recruited 20 individuals in each of the following categories: Alzheimer's disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and healthy control (HC). All participants completed the 3.0T resting-state functional MRI (rs-fMRI) and arterial spin labeling scans in addition to neuropsychological tests. Additionally, the normalized CBF, regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) of individual subjects were compared in the ADS. Moreover, the changes in intrinsic FC were investigated across the ADS using the abnormal rCBF regions as seeds and behavioral correlations. Finally, a support-vector classifier model of machine learning was used to distinguish individuals with ADS from HC.Results: Compared to the HC subjects, patients with AD showed the poorest level of rCBF in the left precuneus (LPCUN) and right middle frontal gyrus (RMFG) among all participants. In addition, there was a significant decrease in the ALFF in the bilateral posterior cingulate cortex (PCC) and ReHo in the right PCC. Moreover, RMFG- and LPCUN-based FC analysis revealed that the altered FCs were primarily located in the posterior brain regions. Finally, a combination of altered rCBF, ALFF, and ReHo in posterior cingulate cortex/precuneus (PCC/PCUN) showed a better ability to differentiate ADS from HC, AD from SCD and MCI, but not MCI from SCD.Conclusions: The study demonstrated the significance of an altered rCBF and brain activity in the early stages of ADS. These findings, therefore, present a potential diagnostic neuroimaging-based biomarker in ADS. Additionally, the study provides a better understanding of the pathophysiology of AD.

The Structural and Functional Neuroanatomy of Post-Stroke Depression and Executive Dysfunction: A Review of Neuroimaging Findings and Implications for Treatment.

Post-stroke depression and executive dysfunction co-occur and are highly debilitating. Few treatments alleviate both depression and executive dysfunction after stroke. Understanding the brain network changes underlying post-stroke depression with executive dysfunction can inform the development of targeted and efficacious treatment. In this review, we synthesize neuroimaging findings in post-stroke depression and post-stroke executive dysfunction and highlight the network commonalities that may underlie this comorbidity. Structural and functional alterations in the cognitive control network, salience network, and default mode network are associated with depression and executive dysfunction after stroke. Specifically, post-stroke depression and executive dysfunction are both linked to changes in intrinsic functional connectivity within resting state networks, functional over-connectivity between the default mode and salience/cognitive control networks, and reduced cross-hemispheric frontoparietal functional connectivity. Cognitive training and noninvasive brain stimulation targeted at these brain network abnormalities and specific clinical phenotypes may help advance treatment for post-stroke depression with executive dysfunction.

Effect of age at time of injury on long-term changes in intrinsic functional connectivity in traumatic brain injury

ABSTRACT Background Alterations in resting-state functional connectivity (rsFC) occur in the acute and chronic phases following traumatic brain injury (TBI); however, few studies have assessed long-term (>1 year) changes in rsFC. Methods Resting-state functional magnetic resonance imaging (rsfMRI) scans were obtained from the Federal Interagency Traumatic Brain Injury Research Informatics Systems. Patients with primarily mild TBI (n = 39) completed rsfMRI scans at the sub-acute (~10 days) and long-term (~18 months) phases. We examined changes in voxel-based rsFC from anterior medial prefrontal cortex (aMPFC) and posterior cingulate cortex (PCC) seeds in the default mode network (DMN) between both phases. The effect of age at the time of injury on long-term rsFC was also examined. Results Increased rsFC from the aMPFC and the PCC to frontal and temporal regions was shown at ~18-months post-injury. Widespread increases in rsFC from the aMPFC and between the PCC and frontal regions were shown for younger patients at time of injury, but limited increases of rsFC were noted at ~18 months in older patients. Conclusion Long-term increases in rsFC were found following TBI, but age at the time of injury was associated with distinct rsFC profiles suggesting that younger patients show greater increases in rsFC over time.

T141. EFFECTS OF MENSTRUAL CYCLE ON RESTING STATE FUNCTIONAL CONNECTIVITY IN SCHIZOPHRENIA: A FUNCTIONAL MRI STUDY

BackgroundThe menstrual cycle is a favorable model for examining the influence of ovarian hormones on cognition, emotion and brain functions. Ovarian hormones have substantial effects on task-related brain activity, but their impacts on functional connectivity at rest have been investigated by a few studies conducted with healthy individuals and these pre-existing findings are inconsistent. As for schizophrenia, different influences of ovarian hormones were reported. For instance, the estrogen hypothesis of schizophrenia has suggested that estrogen plays a neuroprotective role in the pathophysiology of this disorder. The present study investigates resting state functional connectivity (RS-FC) alterations related to menstrual cycle phase and/or hormone levels in patients with schizophrenia and healthy controls and aims to contribute to the understanding of the effects of ovarian hormones on the pathogenesis of schizophrenia and brain functions.MethodsThe study was conducted with 13 women with schizophrenia (the mean of age: 32 ± 7.67) and 13 healthy women (the mean of age: 30.08 ± 7.27). Resting state functional Magnetic Resonance Imaging (fMRI) scanning, as well as hormonal and clinical assessments, were applied to each participant twice, during two menstrual cycle phases: early follicular (Days 2–6; low estrogen/progesterone) and mid-luteal (Days 20–22; high estrogen/progesterone). The serum hormone levels of estradiol, progesterone, prolactin (only in the patients), follicle-stimulating and luteinizing were assessed. The clinical assessment interviews included the Brief Psychiatric Rating Scales, the Clinical Global Impression (only for the patients), the Global Assessment of Functioning and the Calgary Depression Rating Scale for Schizophrenia (for both groups).ResultsOur findings revealed that no cycle phase-related alterations existed in RS-FC in both groups. However, specific correlations between each hormone and RS-FC were found in both cycle phases for two groups. In the patients, estrogen was positively correlated with the auditory network (AN) connectivity in the left amygdala at the early follicular phase. In the controls, the positive correlations to progesterone were found in the precuneus for the connectivity of the posterior default mode network (DMN) and the left-frontoparietal network (FPN) during the early follicular phase. Also, progesterone was negatively correlated with the executive control network (ECN) connectivity in the right superior frontal gyrus at the mid-luteal phase in the controls. Furthermore, the patients had lower progesterone levels during the mid-luteal phase compared to the controls (p<0.05). The severity of the psychotic symptoms of the patients didn’t change between the cycle phases.DiscussionTo our knowledge, this is the first study to examine the influence of the menstrual cycle on the brain’s RS-FC in schizophrenia. Our results indicated that the effects of the menstrual cycle on RS-FC were more prominent in the controls rather than the patients with schizophrenia; and that the findings for the patient group may be associated with the additional mechanisms responsible from schizophrenia. This might imply that differentiating the menstrual cycle effects is difficult in a complex disorder such as schizophrenia. The results obtained from the controls are consistent with the previous findings indicating that the menstrual cycle effects might be associated with the connectivity of the DMN and cognition-related networks. Moreover, our results suggested that estrogen might have a modulating effect on the intrinsic functional connectivity changes in the patients, while progesterone, might mediate to that in the controls.

Changed functional connectivity at rest in functional illiterates after extensive literacy training

BackgroundAbout 6.2 million adults in Germany cannot read and write properly despite attending school for several years. They are considered to be functional illiterates (FI). Since the ability to read and write is crucial for being employed and socially accepted, we developed a special literacy training to overcome these deficits.MethodsIn this study, we investigate training-related changes in intrinsic functional connectivity (iFC) at rest in a group of 20 FI and 20 adult normal readers using resting state functional magnetic resonance imaging (rsfMRI). We used independent component analysis (ICA) to define different networks.ResultsBefore training, the between group analysis showed increased iFC in FI in a left-fronto-parietal network (LFPN; anterior insula, medial frontal cortex, lateral and frontal parietal regions) and in the Basal Ganglia network (BGN: thalamus, caudate, putamen, pallidum, amygdala, supplementary motor cortex and cingulate gyrus). Furthermore, the Visual Network-1 (VN1; temporal occipital fusiform gyrus, lateral occipital cortex, occipital pole, lingual gyrus, thalamus) showed decreased iFC in FI. After training the FI group showed reversal of the “hyperconnectivity” in middle frontal gyrus and in the frontal orbital cortex and between supramarginal gyrus and the BGN. Furthermore, functional connectivity increased in FI VN1 (lateral occipital cortex, insular cortex). These changes in connectivity correlated with gains in reading speed and spelling accuracy.ConclusionsThese findings show that poor reading and writing abilities are associated with abnormalities in iFC in several brain areas subserving cognitive processes important for reading. Intensive literacy training induces changes in the functional connectivity between and within neural networks important for literacy skills.

Intrinsic functional connectivity in social anxiety disorder with and without comorbid attention deficit hyperactivity disorder

Neuroimaging research about social anxiety disorder (SAD) points to hyperactivity in the fear circuit and altered connectivity between the fear circuit and the intrinsic connectivity networks that modulate it. We investigated intrinsic functional connectivity changes in SAD patients by taking into consideration the commonly overlooked comorbidity of attention deficit hyperactivity disorder (ADHD). We compared intrinsic functional connectivity alterations in 16 patients with pure SAD, 18 patients with SAD and comorbid ADHD and 21 healthy controls using seed-to-voxel functional connectivity analyses. Hypoconnectivity of the right fusiform gyrus with the left lingual gyrus was the unique difference between whole SAD group and healthy controls, while in the pure SAD group the fusiform gyrus displayed hypoconnectivity with the posterior default mode network (DMN) regions. In contrast, ADHD comorbidity was associated with hyperconnectivities of the salience network (SN) with the fusiform cortex and the posterior DMN regions, and hyperconnectivities of the posterior DMN with visual, somatosensory and motor cortices. The dichotomic dissociation of the SAD related functional connectivity changes into hypoconnectivities in the pure SAD group vs hyperconnectivities in the SAD-ADHD group leads also to the question, whether ADHD treatment can be considered an alternative for selected SAD cases.

Differential intrinsic functional connectivity changes in semantic variant primary progressive aphasia.

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA.Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes.Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease.

Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome

To determine intrinsic functional connectivity (IFC) related to symptom changes induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual disorder induced by entrainment to oscillating motion. Twenty right-handed women (mean age: 52.9 ± 12.6 years; mean duration illness: 35.2 ± 24.2 months) with MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over consecutive days. High-density (128-channel) resting-state EEG were recorded prior to and following treatment sessions and analyzed using a group-level independent component (IC) analysis. IFC between 19 ICs was quantified by inter-IC phase coherence (ICPC) in six frequency bands (delta, theta, low alpha, high alpha, beta, gamma). Correlational analyses between IFCs and symptoms were performed. Symptom improvement after rTMS was significantly correlated with (1) an increase in low alpha band (8–10 Hz) IFC but a decrease of IFC in all other bands, and (2) high baseline IFC in the high alpha (11–13 Hz) and beta bands (14–30 Hz). Most treatment related IFC changes occurred between frontal and parietal regions with a linear association between the degree of symptom improvement and the number of coherent IFC changes. Frequency band and region specific IFC changes correlate with and can predict symptom changes induced by rTMS over DLPFC in MdDS. MdDS symptom response correlates with high baseline IFC in most frequency bands. Treatment induced increase in long-range low alpha IFC and decreases in IFC in other bands as well as the proportion of coherent IFC changes correlate with symptom reduction.

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model

The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during epileptogenesis were examined by graph theoretical network analysis. Interestingly, increase in the power of low frequency oscillations was observed during the latent period. These results suggest that, even if there are no apparent ictal seizure events during the latent period, there are ongoing changes in the rsFC in the epileptic brain. Furthermore, these results suggest that the pathophysiology of epilepsy may be related to widespread altered intrinsic functional connectivity. These findings can help enhance our understanding of epileptogenesis, and accordingly, changes in intrinsic functional connectivity can serve as an early diagnosis.

Changes in intrinsic functional connectivity and group relevant salience: The case of sport rivalry.

Studies have shown that attending to salient group relevant information could increase the BOLD activity across distributed neural networks. However, it is unclear how attending to group relevant information changes the functional connectivity across these networks. We investigated this issue combining resting states and task-based fMRI experiment. The task involved football fans learning associations between arbitrary geometric shapes and the badges of in-group, the rival and the neutral football teams. Upon learning, participants viewed different badge/shape pairs and their task was to judge whether the viewed pair was a match or a mismatch. For whole brain analyses increased activity was found in the IFG, DLPFC, AI, fusiform gyrus, precuneus and pSTS (all in the left hemisphere) for the rival over the in-group mismatch. Further, the ROI analyses revealed larger beta-values for the rival badge in the left pSTS, left AI and the left IFG. However, larger beta-values were found in the left pSTS and the left IFG (but not AI) for the in-group shape. The intrinsic functional connectivity analyses revealed that compare to the pre-task, post task functional connectivity was decreased between the left DLPFC and the left AI. In contrast, it was increased between the left IFG and the left AI and this was correlated with the difference in RT for the rival vs. in-group team. Our findings suggest that attending to group relevant information differentially affects the strength of functional coupling in attention networks and this can be explained by the saliency of the group relevant information.