Lennox-Gastaut syndrome and phenotype: Secondary network epilepsies.
Epilepsia. 2014 Jun 5;
Authors: Archer JS, Warren AE, Stagnitti MR, Masterton RA, Abbott DF, Jackson GD
OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike-and-wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox-Gastaut-like phenotype and cortical lesions. We wished to explore the interaction between cerebral networks and lesions in this group.
METHODS: 3 Tesla electroencephalography-functional magnetic resonance imaging (EEG-fMRI) on six subjects with Lennox-Gastaut phenotype and a structural lesion. Timings of SSW and PFA events were used in an event-related fMRI analysis, and to estimate the time course of the hemodynamic response from key regions.
RESULTS: (1) PFA-robust fMRI signal increases were observed in frontal and parietal association cortical areas, thalamus, and pons, with simultaneous increases in both "attention" and resting-state (default mode) networks, a highly unusual pattern. (2) SSW showed mixed increased and decreased fMRI activity, with preevent increases in association cortex and thalamus, and then prominent postevent reduction. There was decreased fMRI activity in primary cortical areas. (3) Lesion-variable fMRI increases were observed during PFA and SSW discharges. Three subjects who proceeded to lesionectomy are >1 year seizure-free.
SIGNIFICANCE: We conceptualize Lennox-Gastaut phenotype as a being a network epilepsy, where key cerebral networks become autonomously unstable. Epileptiform activity in Lennox-Gastaut phenotype, and by implication in LGS, appears to be amplified and expressed through association cortical areas, possibly because the attention and default-mode networks are widely interconnected, fundamental brain networks. Seizure freedom in the subjects who proceeded to lesionectomy suggests that cortical lesions are able to establish and maintain this abnormal unstable network behavior. LGS may be considered a secondary network epilepsy because the unifying epileptic manifestations of the disorder, including PFA and SSW, reflect network dysfunction, rather than the specific initiating process. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
PMID: 24902608 [PubMed - as supplied by publisher]
Intrinsic resting-state activity predicts working memory brain activation and behavioral performance.
Hum Brain Mapp. 2013 Dec;34(12):3204-15
Authors: Zou Q, Ross TJ, Gu H, Geng X, Zuo XN, Hong LE, Gao JH, Stein EA, Zang YF, Yang Y
Although resting-state brain activity has been demonstrated to correspond with task-evoked brain activation, the relationship between intrinsic and evoked brain activity has not been fully characterized. For example, it is unclear whether intrinsic activity can also predict task-evoked deactivation and whether the rest-task relationship is dependent on task load. In this study, we addressed these issues on 40 healthy control subjects using resting-state and task-driven [N-back working memory (WM) task] functional magnetic resonance imaging data collected in the same session. Using amplitude of low-frequency fluctuation (ALFF) as an index of intrinsic resting-state activity, we found that ALFF in the middle frontal gyrus and inferior/superior parietal lobules was positively correlated with WM task-evoked activation, while ALFF in the medial prefrontal cortex, posterior cingulate cortex, superior frontal gyrus, superior temporal gyrus, and fusiform gyrus was negatively correlated with WM task-evoked deactivation. Further, the relationship between the intrinsic resting-state activity and task-evoked activation in lateral/superior frontal gyri, inferior/superior parietal lobules, superior temporal gyrus, and midline regions was stronger at higher WM task loads. In addition, both resting-state activity and the task-evoked activation in the superior parietal lobule/precuneus were significantly correlated with the WM task behavioral performance, explaining similar portions of intersubject performance variance. Together, these findings suggest that intrinsic resting-state activity facilitates or is permissive of specific brain circuit engagement to perform a cognitive task, and that resting activity can predict subsequent task-evoked brain responses and behavioral performance.
PMID: 22711376 [PubMed - indexed for MEDLINE]
Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.
Brain Connect. 2014 Jun 5;
Authors: Niesters M, Sitsen E, Oudejans L, Vuyk J, Aarts L, Rombouts SA, de Rover M, Khalili-Mahani N, Dahan A
Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to 8 predefined and 7 thalamic resting-state networks and measured before, and 1 and 2 hours after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-minute intervals on non-deafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (ie. pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic resting-state networks. A significant enhancement of pain sensitivity on non-deafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve (mean (SEM)): 190.4 (33.8) versus 13.7 (7.2); p < 0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.
PMID: 24901040 [PubMed - as supplied by publisher]
Evolution of functional connectivity of brain networks and their dynamic interaction in temporal lobe epilepsy.
Brain Connect. 2014 Jun 5;
Authors: Morgan VL, Abou-Khalil B, Rogers B
This study presents a cross-sectional investigation of functional networks in temporal lobe epilepsy (TLE) as they evolve over years of disease. Networks of interest were identified based on a priori hypotheses: the network of seizure propagation ipsilateral to the seizure focus, the same regions contralateral to seizure focus, the cross hemisphere network of the same regions, and a cingulate midline network. Resting functional magnetic resonance imaging data were acquired for twenty minutes in twelve unilateral TLE patients, and twelve age and gender matched healthy controls. Functional changes within and between the four networks as they evolve over years of disease were quantified by standard measures of static functional connectivity and novel measures of dynamic functional connectivity. The results suggest an initial disruption of cross hemispheric networks and an increase in static functional connectivity in the ipsilateral temporal network accompanying the onset of TLE seizures. As seizures progress over years, the static functional connectivity across the ipsilateral network diminishes, while dynamic functional connectivity measures show the functional independence of this ipsilateral network from the network of midline regions of the cingulate declines. This implies a gradual breakdown of the seizure onset and early propagation network involving the ipsilateral hippocampus and temporal lobe as it becomes more synchronous with the network of regions responsible for secondary generalization of the seizures, a process that may facilitate the spread of seizures across the brain. Ultimately, the significance of this evolution may be realized in relating it to symptoms and treatment outcomes of TLE.
PMID: 24901036 [PubMed - as supplied by publisher]
Lasting Impact of Regret and Gratification on Resting Brain Activity and Its Relation to Depressive Traits.
J Neurosci. 2014 Jun 4;34(23):7825-7835
Authors: Eryilmaz H, Van De Ville D, Schwartz S, Vuilleumier P
Obtaining lower gains than rejected alternatives during decision making evokes feelings of regret, whereas higher gains elicit gratification. Although decision-related emotions produce lingering effects on mental state, neuroscience research has generally focused on transient brain responses to positive or negative events, but ignored more sustained consequences of emotional episodes on subsequent brain states. We investigated how spontaneous brain activity and functional connectivity at rest are modulated by postdecision regret and gratification in 18 healthy human subjects using a gambling task in fMRI. Differences between obtained and unobtained outcomes were manipulated parametrically to evoke different levels of regret or gratification. We investigated how individual personality traits related to depression and rumination affected these responses. Medial and ventral prefrontal areas differentially responded to favorable and unfavorable outcomes during the gambling period. More critically, during subsequent rest, rostral anterior and posterior cingulate cortex, ventral striatum, and insula showed parametric response to the gratification level of preceding outcomes. Functional coupling of posterior cingulate with striatum and amygdala was also enhanced during rest after high gratification. Regret produced distinct changes in connectivity of subgenual cingulate with orbitofrontal cortex and thalamus. Interestingly, individual differences in depressive traits and ruminations correlated with activity of the striatum after gratification and orbitofrontal cortex after regret, respectively. By revealing lingering effects of decision-related emotions on key nodes of resting state networks, our findings illuminate how such emotions may influence self-reflective processing and subsequent behavioral adjustment, but also highlight the malleability of resting networks in emotional contexts.
PMID: 24899706 [PubMed - as supplied by publisher]
Resting-state brain activation correlates with short-time antidepressant treatment outcome in drug-naïve patients with major depressive disorder.
J Int Med Res. 2014 Jun 4;
Authors: Wang LJ, Kuang WH, Xu JJ, Lei D, Yang YC
OBJECTIVE: A resting-state functional magnetic resonance imaging study (fMRI) to investigate pretreatment regional differences in brain function, in patients with early treatment responsive (ERD) and early treatment nonresponsive (END) major depressive disorder (MDD).
METHODS: Patients with MDD and healthy control subjects underwent fMRI. Intrinsic neural activity at baseline was evaluated via amplitude of low-frequency fluctuations (ALFF). Antidepressant treatment was initiated after MRI. All patients received selective serotonin reuptake inhibitor type antidepressants at the minimum effective dose.
RESULTS: There were significant differences in brain activity between patients (n = 56) and control subjects (n = 33). Brain activity in patients with ERD (n = 26) differed from those with END (n = 30) in the lingual gyrus and cerebellum. There was a significantly correlation between activity in these regions and disease duration in patients with ERD, and with amelioration of depressive symptoms in patients with END.
CONCLUSIONS: Brain regions related to the neural mechanism of MDD early treatment outcome were identified. These regions may have important implications for the treatment of MDD.
PMID: 24898399 [PubMed - as supplied by publisher]
Safety of EEG-fMRI recordings in newborn infants at 3T: a study using a baby-size phantom.
Clin Neurophysiol. 2014 May;125(5):941-6
Authors: Vanhatalo S, Alnajjar A, Nguyen VT, Colditz P, Fransson P
OBJECTIVE: We aimed to study EEG electrode temperatures during MRI recordings using a neonatal-size phantom to establish the safety of neonatal EEG-MRI.
METHODS: We constructed a phantom set-up for co-registration of EEG and MRI measurements with newborn size configurations. The set-up consisted of a spherical glass phantom fitted with a customised MRI-compatible 64-channel EEG cap and EEG amplifier. Temperatures were recorded during and after five different scanning sequences (two T2∗ sensitised BOLD fMRI, one T1-weighted and two T2-weighted spin echo) in five electrode locations using a thermistor that was integrated into the electrode housing. A temperature increase >4°C was defined a priori as the safety limit.
RESULTS: During fMRI and T1 sequences, none of the electrodes showed meaningful temperature changes. Only one MRI sequence (T2 with Max turbo factor 25; SAR 89%) caused temperature increase in one electrode (Fpz; +4.1°C) that slightly exceeded our predefined safety limit, while the conventional T2 sequence was within safety limits (up to +1.7°C).
CONCLUSIONS: Co-registration of EEG and fMRI can be considered safe in babies with respect to electrode heating, which is the primary safety concern.
SIGNIFICANCE: The present findings open up a possibility to commence studies where EEG and MRI/fMRI are co-registered in human babies. Such studies hold significant promise of a better understanding of the early development of brain function and neurovascular coupling.
PMID: 24252394 [PubMed - indexed for MEDLINE]
Emotional Processing and Brain Activity in Youth at High Risk for Alcoholism.
Alcohol Clin Exp Res. 2014 May 29;
Authors: Cservenka A, Fair DA, Nagel BJ
BACKGROUND: Even in the absence of heavy alcohol use, youth with familial alcoholism (family history positive [FHP]) exhibit atypical brain functioning and behavior. Although emotional and cognitive systems are affected in alcohol use disorders (AUDs), little attention has focused on whether brain and behavior phenotypes related to the interplay between affective and executive functioning may be a premorbid risk factor for the development of AUDs in FHP youth.
METHODS: Twenty-four FHP and 22 family history negative (FHN) 12- to 16-year-old adolescents completed study procedures. After exclusion of participants with clinically significant depressive symptoms and those who did not meet performance criteria during an Emotional Go-NoGo task, 19 FHP and 17 FHN youth were included in functional magnetic resonance imaging (fMRI) analyses. Resting state functional connectivity MRI, using amygdalar seed regions, was analyzed in 16 FHP and 18 FHN youth, after exclusion of participants with excessive head movement.
RESULTS: fMRI showed that brain activity in FHP youth, compared with FHN peers, was reduced during emotional processing in the superior temporal cortex, as well as during cognitive control within emotional contexts in frontal and striatal regions. Group differences in resting state amygdalar connectivity were seen bilaterally between FHP and FHN youth. In FHP youth, reduced resting state synchrony between the left amygdala and left superior frontal gyrus was related to poorer response inhibition, as measured during the fMRI task.
CONCLUSIONS: To our knowledge, this is the first study to examine emotion-cognition interactions and resting state functional connectivity in FHP youth. Findings from this research provide insight into neural and behavioral phenotypes associated with emotional processing in familial alcoholism, which may relate to increased risk of developing AUDs.
PMID: 24890898 [PubMed - as supplied by publisher]
fMRI evidence for abnormal resting-state functional connectivity in euthymic bipolar patients.
J Affect Disord. 2014 Aug;165:182-9
Authors: Favre P, Baciu M, Pichat C, Bougerol T, Polosan M
BACKGROUND: Neural substrates of bipolar disorder (BD) have frequently been characterized by dysregulation of fronto-limbic networks that may persist during euthymic periods. Only a few studies have investigated euthymic bipolar patients (BP) functional connectivity at rest. The current study aims to assess resting-state functional connectivity in euthymic BP in order to identify trait abnormalities responsible for enduring mood dysregulation in these patients.
METHODS: Medial prefrontal cortex (mPFC) functional connectivity was investigated in 20 euthymic BP and 20 healthy subjects (HS). The functional connectivity maps were compared across groups using a between-group random effect analysis. Additional region of interest (ROI) analysis focused on mPFC-amygdala functional connectivity as well as correlations between the clinical features in euthymic BP was also conducted.
RESULTS: A significant difference between euthymic BP and HS was observed in terms of connectivity between the mPFC and the right dorsolateral prefrontal cortex (dlPFC). A significant negative correlation between the activity of these regions was found in HS but not in euthymic BP. In addition, euthymic BP showed greater connectivity between mPFC and right amygdala compared to HS, which was also correlated with the duration of the disease.
LIMITATIONS: The BP group was heterogeneous with respect to the bipolarity subtype and the medication. The robustness of results could be improved with an increased sample size.
CONCLUSIONS: Compared to HS, the euthymic BP showed abnormal decoupling (decreased functional connectivity) activity between mPFC-dlPFC and hyperconnectivity (increased functional connectivity) and between mPFC and amygdala. These abnormalities could underlie the pathophysiology of BD, and may deteriorate further in accordance with disease duration.
PMID: 24882198 [PubMed - in process]
Resting network is composed of more than one neural pattern: an fMRI study.
Neuroscience. 2014 May 29;
Authors: Lee TW, Northoff G, Wu YT
In resting state, the dynamics of blood oxygen level-dependent signals recorded by functional magnetic resonance imaging (fMRI) showed reliable modular structures. To explore the network property, previous research used to construct an adjacency matrix by Pearson's correlation and prune it using stringent statistical threshold. However, traditional analyses may lose useful information at middle to moderate high correlation level. This resting fMRI study adopted full connection as a criterion to partition the adjacency matrix into composite sub-matrices (neural patterns) and investigated the associated community organization and network features. Modular consistency across subjects was assessed using scaled inclusivity index. Our results disclosed 2 neural patterns with reliable modular structures. Concordant with the results of traditional intervention, community detection analysis showed that neural pattern 1, the sub-matrix at highest correlation level, was composed of sensory-motor, visual associative, default mode/midline, temporal limbic and basal ganglia structures. The neural pattern 2 was situated at middle to moderate high correlation level and comprised 2 larger modules, possibly associated with mental processing of outer world (such as visuo-associative, auditory and sensory-motor networks) and inner homeostasis (such as default-mode, midline and limbic systems). Graph theoretical analyses further demonstrated that the network feature of neural pattern 1 was more local and segregate, whereas that of neural pattern 2 was more global and integrative. Our results suggest that future resting fMRI research may take the neural pattern at middle to moderate high correlation range into consideration, which has long been ignored in extant literature. The variation of neural pattern 2 could be relevant to individual characteristics of self-regulatory functions, and the disruption in its topology may underlie the pathology of several neuropsychiatric illnesses.
PMID: 24881572 [PubMed - as supplied by publisher]
Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy.
Brain Topogr. 2014 Jun 1;
Authors: Doucet GE, Sharan A, Pustina D, Skidmore C, Sperling MR, Tracy JI
Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.
PMID: 24881003 [PubMed - as supplied by publisher]
Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.
Neuroimage. 2014 May 28;
Authors: Shou H, Eloyan A, Nebel MB, Mejia A, Pekar JJ, Mostofsky S, Caffo B, Lindquist MA, Crainiceanu CM
Resting-state functional magnetic resonance imaging (rs-fMRI) is used to investigate synchronous activations in spatially distinct regions of the brain, which are thought to reflect functional systems supporting cognitive processes. Analyses are often performed using seed-based correlation analysis, allowing researchers to explore functional connectivity between data in a seed region and the rest of the brain. Using scan-rescan rs-fMRI data, we investigate how well the subject-specific seed-based correlation map from the second replication of the study can be predicted using data from the first replication. We show that one can dramatically improve prediction of subject-specific connectivity by borrowing strength from the group correlation map computed using all other subjects in the study. Even more surprisingly, we found that the group correlation map provided a better prediction of a subject's connectivity than the individual's own data. While further discussion and experimentation is required to understand how this can be used in practice, results indicate that shrinkage-based methods that borrow strength from the population mean should play a role in rs-fMRI data analysis.
PMID: 24879924 [PubMed - as supplied by publisher]
Test-Retest Reliabilities of Resting-state FMRI Measurements in Human Brain Functional Connectomics: A Systems Neuroscience Perspective.
Neurosci Biobehav Rev. 2014 May 26;
Authors: Zuo XN, Xing XX
Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.
PMID: 24875392 [PubMed - as supplied by publisher]
Time of Acquisition and Network Stability in Pediatric Resting-State Functional MRI.
Brain Connect. 2014 May 29;
Authors: White T, Muetzel R, Schmidt M, Langeslag SJ, Jaddoe V, Hofman A, Calhoun VD, Verhulst FC, Tiemeier H
Resting-state functional magnetic resonance imaging (rs-fMRI) has been shown to elucidate reliable patterns of brain networks in both children and adults. Studies in adults have shown that rs-fMRI acquisition times of approximately five to six minutes provide adequate sampling to produce stable spatial maps of a number of different brain networks. However, it is unclear if the acquisition time translates directly to studies of children. While there are many similarities between the brains of children and adults, many differences are also evident. Children have increased metabolism, differences in brain morphology and connectivity strengths, greater brain plasticity, and increased brain noise. Furthermore, there are differences in physiologic parameters, such as heart and respiratory rates, and compliance of the blood vessels. These developmental differences could translate into different acquisition times for rs-fMRI studies in pediatric populations. Longer scan times, however, increase the subject burden and the risk for greater movement, especially in children. Thus, the goal of this study was to assess the optimum acquisition time of rs-fMRI to extract stable brain networks in school-age children. We utilized fuzzy set theory in 84 six-to-eight year-old children and found that eight networks, including the default mode, salience, frontal, left frontoparietal, right frontoparietal, sensorimotor, auditory, and visual networks, all stabilized after approximately 5½ minutes. The sensorimotor network showed the least stability whereas the salience and auditory networks showed the greatest stability. A secondary analysis using dual regression confirmed these results. In conclusion, in young children with little head motion, rs-fMRI acquisition times of approximately 5½ minutes can extract the full complement of brain networks.
PMID: 24874884 [PubMed - as supplied by publisher]
Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting-state FMRI study.
Neural Plast. 2014;2014:549162
Authors: Han L, Zhaohui L, Fei Y, Ting L, Pengfei Z, Wang D, Cheng D, Pengde G, Xiaoyi H, Xiao W, Rui L, Zhenchang W
Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.
PMID: 24872895 [PubMed - in process]
In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.
Brain Connect. 2014 May 28;
Authors: Klupp E, Förster S, Grimmer T, Tahmasian M, Yakushev I, Sorg C, Yousefi B, Drzezga A
In patients with Alzheimer's disease (AD) prominent hypometabolism has been observed in brain-regions with minor amyloid load. These hypometabolism only (HO)-areas cannot be explained merely as consequence of local amyloid-toxicity. Aim of this multimodal imaging study was to explore if such HO-phenomenon may be related to pathologies in functionally connected, remote brain-regions. 19 AD-patients and 15 matched controls underwent examinations with [11C]PiB-PET and [18F]FDG-PET. Voxel-based statistical group comparisons were performed to obtain maps of significantly elevated amyloid-burden and reduced cerebral glucose metabolism respectively in patients. An HO-area was identified by subtraction of equally thresholded result-maps (hypometabolism minus amyloid-burden). To identify the network typically functionally connected to this HO-area, it was used as seed-region for a functional connectivity analysis in resting state fMRI data of 17 elderly healthy controls, The resulting intrinsic connectivity network (HO-ICN) was retransferred into the brains of AD-patients to be able to analyze pathologies within this network in the PET-datasets. Most prominent HO-area was detected in the left middle frontal gyrus of AD-patients. The HO-ICN in healthy controls showed major overlap with brain areas significantly affected by both, amyloid-deposition and hypometabolism in patients. This association was substantiated by the results of ROI-based and voxel-wise correlation-analyses, which revealed strong correlations between the degree of hypometabolism within the HO-region and within the HO-ICN. These results support the notion that hypometabolism in brain regions not strongly affected by locoregional amyloid-pathology may be related to on-going pathologies in remote but functionally connected regions, i.e. by reduced neuronal input from these regions.
PMID: 24870443 [PubMed - as supplied by publisher]
Two distinct neural mechanisms underlying indirect reciprocity.
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):3990-5
Authors: Watanabe T, Takezawa M, Nakawake Y, Kunimatsu A, Yamasue H, Nakamura M, Miyashita Y, Masuda N
Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.
PMID: 24591599 [PubMed - indexed for MEDLINE]
Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.
Hum Brain Mapp. 2014 May 28;
Authors: Huang Z, Wang Z, Zhang J, Dai R, Wu J, Li Y, Liang W, Mao Y, Yang Z, Holland G, Zhang J, Northoff G
Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
PMID: 24867379 [PubMed - as supplied by publisher]
Independent component analysis of resting state activity in pediatric obsessive-compulsive disorder.
Hum Brain Mapp. 2014 May 28;
Authors: Gruner P, Vo A, Argyelan M, Ikuta T, Degnan AJ, John M, Peters BD, Malhotra AK, Uluğ AM, Szeszko PR
Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9-17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
PMID: 24867148 [PubMed - as supplied by publisher]
Resting-state functional connectivity abnormalities in patients with obsessive-compulsive disorder and their healthy first-degree relatives.
J Psychiatry Neurosci. 2014 Jul 1;39(4):130220
Authors: Hou JM, Zhao M, Zhang W, Song LH, Wu WJ, Wang J, Zhou DQ, Xie B, He M, Guo JW, Qu W, Li HT
BACKGROUND: Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical-striatal-thalamic-cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives.
METHODS: We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach.
RESULTS: We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus.
LIMITATIONS: Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings.
CONCLUSION: Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.
PMID: 24866415 [PubMed - as supplied by publisher]