Resting-state Function Research Articles

EP 77. Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) – Potential markers for neurodegeneration –

Objectives Idiopathic REM sleep behavior disorder (RBD) is a parasomnia characterized by the loss of physiological atonia of skeletal muscles during dream sleep. This leads to enactment of dream content with nocturnal behavior such as flailing of the arms, kicking and/or vocalization ( Boeve, 2010 ). RBD may be the initial manifestation of neurodegenerative α -synucleinopathies (Parkinson’s disease [PD], Parkinson’s disease dementia [PDD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) ( Boeve, 2010 , Postuma et al., 2009 ). Nevertheless, individual prognoses concerning the type of subsequent disease and time of phenoconversion are still challenging. By concentrating recent brain imaging findings on the radionuclide imaging techniques of single photon emission computerized tomography (SPECT) and positron emission tomography (PET), structural and functional magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and transcranial sonography (TCS) in RBD, we aimed to identify potential neuroimaging markers enabling a more accurate prediction of neurodegenerative processes in this disease. Methods We ran electronic searches for English peer-reviewed journal articles indexed in the PubMed database using the following keywords: “(REM sleep behavior disorder OR RBD) AND (imaging OR neuroimaging OR TCS OR PET OR SPECT OR MRI OR MRS)”. In addition, we browsed through reference lists and published reviews focusing on this or similar topics. We only considered studies assessing the human brain. Furthermore, solely studies that addressed idiopathic RBD without comorbid mental disorders, neurologic or neurodegenerative diseases were included, unless these studies compared RBD patients additionally suffering from comorbidities to patients with idiopathic RBD. Results Overall, PET and SPECT (n = 20 studies) are of best prognostic value for the identification of RBD patients being at risk to phenoconvert. Moreover, these techniques are useful in the early or even premanifest differential diagnosis of emerging α -synucleinopathies such as PD, DLB and MSA ( Fig. 1 ). Conventional structural MRI (n = 7 studies) so far mostly revealed unspecific findings in RBD. In contrast, the few studies focusing on diffusion-weighted structural MRI (n = 2 studies), functional resting-state MRI (n = 1 study), imaging of brain iron content (n = 1 study) and phosphor and proton MRS (n = 2 studies) provided promising results for the early identification of progressive neurodegeneration in RBD patients. Lastly, although sensitivity is limited, TCS (n = 7 studies) is helpful in the identification of RBD patients being at a specific risk for the development of PD ( Fig. 1 ). Conclusion While PET, SPECT and TCS already offer sensitive imaging markers to identify RBD patients at risk for progressive neurodegeneration, studies focusing on MRI and MRS are more limited. Further imaging research applying multimodal approaches is encouraged to enhance accuracy of prognosis. Additionally, more longitudinal studies are warranted to validate findings from cross-sectional studies on RBD progression and risk of subsequent phenoconversion. Aside from enabling reliable prognoses on a single-subject-level in the near future, this might give further insight into RBD pathophysiology, and finally augment the development of intervention strategies and disease-modifying therapies.

Examining Functional Resting-State Connectivity in Psychosis and Its Subgroups in the Bipolar-Schizophrenia Network on Intermediate Phenotypes Cohort

BackgroundWe sought to examine resting-state functional magnetic resonance imaging connectivity measures in psychotic patients to both identify cumulative differences across psychosis and subsequently probe deficits across conventional DSM-IV diagnoses and a newly identified classification using cognitive/neurophysiological data (Biotypes). MethodsWe assessed 1125 subjects, including healthy control subjects, probands (schizophrenia, schizoaffective disorder, psychotic bipolar disorder), and relatives of probands. Probands and relatives were also segregated into Biotype groups (B1–B3, B1R–B3R using a method reported previously). Empirical resting-state functional magnetic resonance imaging networks were derived using independent component analysis. Global psychosis-related abnormalities were first identified. Subsequent post hoc t tests were performed across various diagnostic categories. Follow-up linear mixed model compared significance of within-proband differences across categories. Secondary analyses assessed correlations with biological profile scores. ResultsVoxelwise tests between proband and control subjects revealed nine abnormal networks. Post hoc analysis revealed lower connectivity in most networks for all proband subgroups (DSM and Biotypes). Within-proband effect sizes of discrimination were marginally better for Biotypes over DSM. Reduced connectivity was noted in relatives of patients with schizophrenia in two networks and relatives of patients with psychotic bipolar disorder in one network. Biotype relatives showed similar deficits in one network. Connectivity deficits across four networks were significantly associated with cognitive control profile scores. ConclusionsOverall, we found psychosis-related connectivity deficits in nine large-scale networks. Deficits in these networks tracked more closely with cognitive control factors, suggesting potential implications for disease profiling and therapeutic intervention. Biotypes performed marginally better in terms of separating out psychosis subgroups compared with conventional DSM or psychiatric diagnoses.

NEURONAL ACTIVITY DERIVED FROM RESTING STATE FUNCTIONAL MRI: A POTENTIAL BIOMARKER FOR ALZHEIMER DISEASE

NEURONAL ACTIVITY DERIVED FROM RESTING STATE FUNCTIONAL MRI: A POTENTIAL BIOMARKER FOR ALZHEIMER DISEASE

NEURONAL ACTIVITY DERIVED FROM RESTING STATE FUNCTIONAL MRI: A POTENTIAL BIOMARKER FOR ALZHEIMER'S DISEASE

NEURONAL ACTIVITY DERIVED FROM RESTING STATE FUNCTIONAL MRI: A POTENTIAL BIOMARKER FOR ALZHEIMER'S DISEASE

MEDIATION OF EPISODIC MEMORY PERFORMANCE BY THE EXECUTIVE FUNCTION NETWORK IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT: A RESTING-STATE FUNCTIONAL MRI STUDY

MEDIATION OF EPISODIC MEMORY PERFORMANCE BY THE EXECUTIVE FUNCTION NETWORK IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT: A RESTING-STATE FUNCTIONAL MRI STUDY

IMPAIRMENT OF RESTING-STATE FUNCTIONAL CONNECTIVITY IN THE DEFAULT-MODE NETWORK CLOSELY TRACKS CSF BIOMARKERS IN MCI

IMPAIRMENT OF RESTING-STATE FUNCTIONAL CONNECTIVITY IN THE DEFAULT-MODE NETWORK CLOSELY TRACKS CSF BIOMARKERS IN MCI

Sensitivity of the resting-state haemodynamic response function estimation to autonomic nervous system fluctuations.

The haemodynamic response function (HRF) is a key component of the blood oxygen level-dependent (BOLD) signal, providing the mapping between neural activity and the signal measured with functional magnetic resonance imaging (fMRI). Most of the time the HRF is associated with task-based fMRI protocols, in which its onset is explicitly included in the design matrix. On the other hand, the HRF also mediates the relationship between spontaneous neural activity and the BOLD signal in resting-state protocols, in which no explicit stimulus is taken into account. It has been shown that resting-state brain dynamics can be characterized by looking at sparse BOLD 'events', which can be retrieved by point process analysis. These events can be then used to retrieve the HRF at rest. Crucially, cardiac activity can also induce changes in the BOLD signal, thus affecting both the number of these events and the estimation of the haemodynamic response. In this study, we compare the resting-state haemodynamic response retrieved by means of a point process analysis, taking the cardiac fluctuations into account. We find that the resting-state HRF estimation is significantly modulated in the brainstem and surrounding cortical areas. From the analysis of two high-quality datasets with different temporal and spatial resolution, and through the investigation of intersubject correlation, we suggest that spontaneous point process response durations are associated with the mean interbeat interval and low-frequency power of heart rate variability in the brainstem.

Imbalance in subregional connectivity of the right temporoparietal junction in major depression.

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc.

ID 99 – Functional connectivity study on repetitive transcranial magnetic stimulation for central post-stroke pain

Objective Central post-stroke pain (CPSP) is one of the most refractory chronic pain syndromes. We and others have reported that repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex relieves pain in patients with CPSP. However, the mechanism underlying the pain relief remains unclear. This study aimed to investigate functional connectivity specific to CPSP and functional connectivity alteration associated with pain relief by rTMS. Methods Subjects were 12 patients with CPSP and 12 age-matched healthy controls. Resting-state function MRI (rs-fMRI) was taken before and after 5 Hz-rTMS of the ipsilesional primary motor cortex in patients, meanwhile rs-fMRI was taken once in controls without the rTMS intervention. rs-fMRI data was preprocessed, and second-level analyses of seed-to-voxel connectivity were implemented. Results The functional connectivity related to the ipsilesional primary motor cortex (FC-M1) was larger in patients than in controls. The alteration of FC-M1 after rTMS negatively correlated with pain relief. Conclusions Our findings suggested that alteration of the functional connectivity might be one of the mechanisms underlying pain relief by rTMS in CPSP. Key message rTMS might affect the functional connectivity related to the stimulation site in patients with CPSP.

Functional resting-state fMRI connectivity correlates with serum levels of the S100B protein in the acute phase of traumatic brain injury.

The S100B protein is an intra-cellular calcium-binding protein that mainly resides in astrocytes in the central nervous system. The serum level of S100B is used as biomarker for the severity of brain damage in traumatic brain injury (TBI) patients. In this study we investigated the relationship between intrinsic resting-state brain connectivity, measured 1–22 days (mean 8 days) after trauma, and serum levels of S100B in a patient cohort with mild-to-severe TBI in need of neuro-intensive care in the acute phase. In line with previous investigations, our results show that the peak level of S100B acquired during the acute phase of TBI was negatively correlated with behavioral measures (Glasgow Outcome Score, GOS) of functional outcome assessed 6 to 12 months post injury. Using a multi-variate pattern analysis-informed seed-based correlation analysis, we show that the strength of resting-state brain connectivity in multiple resting-state networks was negatively correlated with the peak of serum levels of S100B. A negative correspondence between S100B peak levels recorded 12–36 h after trauma and intrinsic connectivity was found for brain regions located in the default mode, fronto-parietal, visual and motor resting-state networks. Our results suggest that resting-state brain connectivity measures acquired during the acute phase of TBI is concordant with results obtained from molecular biomarkers and that it may hold a capacity to predict long-term cognitive outcome in TBI patients.

Gray Matter Volume and Resting-State Functional Connectivity of the Motor Cortex-Cerebellum Network Reflect the Individual Variation in Masticatory Performance in Healthy Elderly People.

Neuroimaging studies have consistently identified brain activation in the motor area and the cerebellum during chewing. In this study, we further investigated the structural and functional brain signature associated with masticatory performance, which is a widely used index for evaluating overall masticatory function in the elderly. Twenty-five healthy elderly participants underwent oral examinations, masticatory performance tests, and behavioral assessments, including the Cognitive Abilities Screening Instrument and the short-form Geriatric Depression Scale. Masticatory performance was assessed with the validated colorimetric method, using color-changeable chewing gum. T1-weighted structural magnetic resonance imaging (MRI) and resting-state function MRI were performed. We analyzed alterations in gray matter volume (GMV) using voxel-based morphometry and resting-state functional connectivity (rsFC) between brain regions using the seed-based method. The structural and functional MRI analyses revealed the following findings: (1) the GMV change in the premotor cortex was positively correlated with masticatory performance. (2) The rsFC between the cerebellum and the premotor cortex was positively correlated with masticatory performance. (3) The GMV changes in the dorsolateral prefrontal cortex (DLPFC), as well as the rsFC between the cerebellum and the DLPFC, were positively correlated with masticatory performance. The findings showed that in the premotor cortex, a reduction of GMV and rsFC would reflect declined masticatory performance. The positive correlation between DLPFC connectivity and masticatory performance implies that masticatory ability is associated with cognitive function in the elderly. Our findings highlighted the role of the central nervous system in masticatory performance and increased our understanding of the structural and functional brain signature underlying individual variations in masticatory performance in the elderly.

Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience.

Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts' and amateurs' resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

A More Global Look at Altered Neural Structure and Resting-State Function in Borderline Personality Disorder

A More Global Look at Altered Neural Structure and Resting-State Function in Borderline Personality Disorder

Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals.

To investigate alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after ultra-rapid opioid detoxification under general anaesthesia (UROD) combined with naltrexone treatment (NMT). Fourteen CCS-dependent individuals were scanned using resting-state fMRI. After UROD and 2weeks of NMT, CCS-dependent individuals were rescanned. Fourteen matched controls were studied at baseline and compared. The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function. After UROD and 2weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral parahippocampal gyrus and right medial orbitofrontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pretreatment. Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals. We offer the first report describing how regional and integral synchronous neural activity occurs after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity. These findings contribute to the understanding of complex systems involved in UROD-NMT effects. • CCS-dependent individuals had reduced ALFF and increased FC at baseline. • UROD treatment can change the regional and integral brain function of CCS-dependent individuals. • Attenuated ALFFs are correlated with the withdrawal syndrome after treatment.

Research on modeling approach of brain function network based on anatomical distance

The number of common neighbor between nodes is applied to the modeling of resting-state brain function network in order to analyze the effect of anatomical distance on the modeling of resting-state brain function network. Three models based on anatomical distance, the number of common neighbor, or anatomical distance and the number of common neighbor are designed. Basing on residuals creates the evaluation criteria for selecting the optimal brain function model network in each class model. The model is selected to simulate the human real brain function network by comparison with real data functional magnetic resonance imaging (fMRI) network. Finally, the result shows that the best model only is based on anatomical distance.

APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.

To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05).APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect.

Characterizing Resting-State Brain Function Using Arterial Spin Labeling.

Arterial spin labeling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the following main categories: (1) resting-state functional connectivity (FC) measurement: the use of ASL-based cerebral blood flow (CBF) measurements as an alternative to the blood oxygen level-dependent (BOLD) technique to assess resting-state FC; (2) the link between network CBF and FC measurements: the use of network CBF as a surrogate of the metabolic activity within corresponding networks; and (3) the study of resting-state dynamic CBF-BOLD coupling and cerebral metabolism: the use of dynamic CBF information obtained using ASL to assess dynamic CBF-BOLD coupling and oxidative metabolism in the resting state. In addition, we summarize some future challenges and interesting research directions for ASL, including slice-accelerated (multiband) imaging as well as the effects of motion and other physiological confounds on perfusion-based FC measurement. In summary, this work reviews the state-of-the-art of ASL and establishes it as an increasingly viable MRI technique with high translational value in studying resting-state brain function.

O028. Thalamo-cortical network changes during the migraine cycle: insights from MRI-based microstructural and functional resting-state network correlation analysis.

O028. Thalamo-cortical network changes during the migraine cycle: insights from MRI-based microstructural and functional resting-state network correlation analysis Gianluca Coppola, Antonio Di Renzo, Emanuele Tinelli, Chiara Lepre, Elisa Iacovelli, Cherubino Di Lorenzo, Giorgio Di Lorenzo, Vincenzo Parisi, Mariano Serrao, Flavia Pauri, Giancarlo Fiermonte, Claudio Colonnese, Jean Schoenen, Francesco Pierelli

Regional Homogeneity of Resting-State Brain Activity Suppresses the Effect of Dopamine-Related Genes on Sensory Processing Sensitivity.

Sensory processing sensitivity (SPS) is an intrinsic personality trait whose genetic and neural bases have recently been studied. The current study used a neural mediation model to explore whether resting-state brain functions mediated the effects of dopamine-related genes on SPS. 298 healthy Chinese college students (96 males, mean age = 20.42 years, SD = 0.89) were scanned with magnetic resonance imaging during resting state, genotyped for 98 loci within the dopamine system, and administered the Highly Sensitive Person Scale. We extracted a “gene score” that summarized the genetic variations representing the 10 loci that were significantly linked to SPS, and then used path analysis to search for brain regions whose resting-state data would help explain the gene-behavior association. Mediation analysis revealed that temporal homogeneity of regional spontaneous activity (ReHo) in the precuneus actually suppressed the effect of dopamine-related genes on SPS. The path model explained 16% of the variance of SPS. This study represents the first attempt at using a multi-gene voxel-based neural mediation model to explore the complex relations among genes, brain, and personality.

Analysis of functional brain networks in patients with subcortical vascular cognitive impairment

Objective To investigate the change of the resting-state brain function of patients with Subcortical Vascular Cognitive Impairment (SVCI) by complex network theory which is based on the graph theory and determine the possible imaging characteristics. Methods 34 patients with SVCI and 22 controls were recruited. All of them were interviewed using a set of neuropsychological tests including mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA), and were subject to the MRI scan. Based on the acquired data, functional network were constructed for the subsequent analysis. Results Both of the two groups showed small-world attributes. The node degree of SVCI group was significantly decreased in the left triangular part of inferior frontal gyrus(-45.58, 29.91, 13.99) and left lingual gyrus(-14.62, -67.56, -4.63), and significantly increased in the right precentral gyrus(41.37, 8.21, 52.09), right rolandic operculum(52.65, -6.25, 14.63), left superior temporal gyrus(-53.16, -20.68, 7.13), right superior temporal gyrus(58.15, -21.78, 6.80) and left middle temporal gyrus(-55.52, -33.80, -2.20). The betweenness centrality of the SVCI group significantly decreased in the left triangular part of inferior frontal gyrus(-45.58, 29.91, 13.99), right anterior cingulate/paracingulate cortex(8.46, 37.01, 15.84), right middle occipital gyrus(37.39, -79.70, 19.42) and left angular gyrus(-42.80, 45.82, 46.74), while it was significantly increased in the right anterior central gyrus(41.37, -8.21, 52.09), right rolandic operculum(52.65, -6.25, 14.63), left inferior occipital gyrus(-36.36, -78.29, -7.84) and left fusiform gyrus(-31.16, -40.30, -20.23). Node degree of left lingual gyrus and betweenness centrality of the left triangular part of inferior frontal gyrus had significantly positive correlation with MoCA. Node degree of left lingual gyrus and the left triangular part of inferior frontal gyrus and betweenness centrality of the left triangular part of inferior frontal gyrus had significantly positive correlation with MMSE. Conclusion Both of the SVCI group and the control group show small-world attributes. The change of the node attributes in some regions of the brain can help to understand the underlying mechanism of the cognitive impairment. Key words: Subcortical vascular cognition impairment; Magnetic resonance imaging; Brain network