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Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

Sun, 03/31/2019 - 18:32

Cognitive slowing and its underlying neurobiology in temporal lobe epilepsy.

Cortex. 2019 Mar 05;117:41-52

Authors: Hwang G, Dabbs K, Conant L, Nair VA, Mathis J, Almane DN, Nencka A, Birn R, Humphries C, Raghavan M, DeYoe EA, Struck AF, Maganti R, Binder JR, Meyerand E, Prabhakaran V, Hermann B

Abstract
Cognitive slowing is a known but comparatively under-investigated neuropsychological complication of the epilepsies in relation to other known cognitive comorbidities such as memory, executive function and language. Here we focus on a novel metric of processing speed, characterize its relative salience compared to other cognitive difficulties in epilepsy, and explore its underlying neurobiological correlates. Research participants included 55 patients with temporal lobe epilepsy (TLE) and 58 healthy controls from the Epilepsy Connectome Project (ECP) who were administered a battery of tests yielding 14 neuropsychological measures, including selected tests from the NIH Toolbox-Cognitive Battery, and underwent 3T MRI and resting state fMRI. TLE patients exhibited a pattern of generalized cognitive impairment with very few lateralized abnormalities. Using the neuropsychological measures, machine learning (Support Vector Machine binary classification model) classified the TLE and control groups with 74% accuracy with processing speed (NIH Toolbox Pattern Comparison Processing Speed Test) the best predictor. In TLE, slower processing speed was associated predominantly with decreased local gyrification in regions including the rostral and caudal middle frontal gyrus, inferior precentral cortex, insula, inferior parietal cortex (angular and supramarginal gyri), lateral occipital cortex, rostral anterior cingulate, and medial orbital frontal regions, as well as three small regions of the temporal lobe. Slower processing speed was also associated with decreased connectivity between the primary visual cortices in both hemispheres and the left supplementary motor area, as well as between the right parieto-occipital sulcus and right middle insular area. Overall, slowed processing speed is an important cognitive comorbidity of TLE associated with altered brain structure and connectivity.

PMID: 30927560 [PubMed - as supplied by publisher]

Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology.

Sun, 03/31/2019 - 18:32
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Intrinsic functional architecture of the non-human primate spinal cord derived from fMRI and electrophysiology.

Nat Commun. 2019 Mar 29;10(1):1416

Authors: Wu TL, Yang PF, Wang F, Shi Z, Mishra A, Wu R, Chen LM, Gore JC

Abstract
Resting-state functional MRI (rsfMRI) has recently revealed correlated signals in the spinal cord horns of monkeys and humans. However, the interpretation of these rsfMRI correlations as indicators of functional connectivity in the spinal cord remains unclear. Here, we recorded stimulus-evoked and spontaneous spiking activity and local field potentials (LFPs) from monkey spinal cord in order to validate fMRI measures. We found that both BOLD and electrophysiological signals elicited by tactile stimulation co-localized to the ipsilateral dorsal horn. Temporal profiles of stimulus-evoked BOLD signals covaried with LFP and multiunit spiking in a similar way to those observed in the brain. Functional connectivity of dorsal horns exhibited a U-shaped profile along the dorsal-intermediate-ventral axis. Overall, these results suggest that there is an intrinsic functional architecture within the gray matter of a single spinal segment, and that rsfMRI signals at high field directly reflect this underlying spontaneous neuronal activity.

PMID: 30926817 [PubMed - in process]

Brain activation in highly superior autobiographical memory: The role of the praecuneus in the autobiographical memory retrieval network.

Sun, 03/31/2019 - 18:32
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Brain activation in highly superior autobiographical memory: The role of the praecuneus in the autobiographical memory retrieval network.

Cortex. 2019 Mar 05;:

Authors: Mazzoni G, Clark A, De Bartolo A, Guerrini C, Nahouli Z, Duzzi D, De Marco M, McGeown W, Venneri A

Abstract
This is the first study to examine functional brain activation in a single case of Highly Superior Autobiographical Memory (HSAM) who shows no sign of obsessive compulsive disorder (OCD). While previous work has documented the existence of HSAM, information about brain areas involved in this exceptional form of memory for personal events relies on structural and resting state connectivity data, with mixed results so far. In this first task-based functional magnetic resonance Imaging (fMRI) study of a normal individual with HSAM, dates were presented as cues and two phases were assessed during memory retrieval, initial access and later elaboration. Results showed that initial access was very fast, did not activate the hippocampus, and involved activation of predominantly posterior visual areas, including the praecuneus. These areas typically become active during later stages of elaboration of personal memories rather than during initial access. Elaboration involved a balanced bilateral activation of most of the autobiographical network areas, rather than the more typical shifts observed in people without HSAM. Overall, the pattern of brain activations, which rests on repeated observations in a single individual, highlights a strong involvement of the praecuneus and an idiosyncratic initial access to personal memory representations. Implications for the nature of personal memories in HSAM are discussed.

PMID: 30926140 [PubMed - as supplied by publisher]

A Review of Functional and Structural Neurobiology of the Action Observation Network in Autism Spectrum Disorder and Developmental Coordination Disorder.

Sun, 03/31/2019 - 18:32
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A Review of Functional and Structural Neurobiology of the Action Observation Network in Autism Spectrum Disorder and Developmental Coordination Disorder.

Brain Sci. 2019 Mar 28;9(4):

Authors: Kilroy E, Cermak SA, Aziz-Zadeh L

Abstract
Recent research has reported motor impairment similarities between children with developmental coordination disorder (DCD) and a subgroup of individuals with autism spectrum disorder (ASD). However, there is a debate as to whether DCD is a co-occurring diagnosis in individuals with ASD and motor impairments (ASDd), or if motor impairments in ASD are distinct from DCD. However, the etiology of motor impairments is not well understood in either disorder. Clarifying comorbidities in ASD is important to determine different etiopathological phenotyping clusters in ASD and to understand the variety of genetic and environmental factors that contribute to the disorder. Furthermore, this distinction has important therapeutic relevance. Here we explore the current neuroimaging findings in ASD and DCD and discusses possible neural mechanisms that underlie similarities and differences between the disorders.

PMID: 30925819 [PubMed]

Intelligence moderates the relationship between age and inter-connectivity of resting state networks in older adults.

Sat, 03/30/2019 - 21:31
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Intelligence moderates the relationship between age and inter-connectivity of resting state networks in older adults.

Neurobiol Aging. 2019 Feb 27;78:121-129

Authors: Lindbergh CA, Zhao Y, Lv J, Mewborn CM, Puente AN, Terry DP, Renzi-Hammond LM, Hammond BR, Liu T, Miller LS

Abstract
Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample consisted of 48 community-dwelling older adults with resting state functional magnetic resonance imaging data. Global inter-connectivity between DMN and 9 other resting state networks was calculated using a novel computational framework based on machine learning. Intellectual functioning (intelligence) was estimated using the Wechsler Test of Adult Reading. A significant, positive relationship was found between age and global inter-network connectivity (r = 0.31, p = 0.029). Moderation analyses yielded a significant age × intelligence interaction term (p = 0.003), such that intelligence attenuated the relationship between age and global inter-network connectivity. Taken together, these results suggest that age is positively associated with global DMN desegregation, possibly due to dedifferentiation or compensation. Intellectual functioning moderates this relationship, such that more intelligent older adults maintain a segregated DMN profile.

PMID: 30925300 [PubMed - as supplied by publisher]

Loneliness and meaning in life are reflected in the intrinsic network architecture of the brain.

Sat, 03/30/2019 - 21:31
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Loneliness and meaning in life are reflected in the intrinsic network architecture of the brain.

Soc Cogn Affect Neurosci. 2019 Mar 29;:

Authors: Mwilambwe-Tshilobo L, Ge T, Chong M, Ferguson MA, Misic B, Burrow AL, Leahy R, Spreng RN

Abstract
Social relationships imbue life with meaning, whereas loneliness diminishes the sense of meaning in life. Yet the extent of interdependence between these psychological constructs remains poorly understood. Loneliness and meaning are associated with different patterns of functional connectivity; however, no studies have investigated this directly. We took a multivariate network approach to examine resting-state fMRI functional connectivity's association with loneliness and meaning in a large cohort of adults (N=942). Loneliness and meaning in life were negatively correlated with one another. In their relationship with individually parcelled whole-brain measures of functional connectivity, a significant and reliable pattern was observed. Greater loneliness was associated with dense, and less modular, connections between default, frontoparietal and externally-directed attention and perceptual networks. A greater sense of life meaning was associated with increased, and more modular, connectivity between default and limbic networks. Low loneliness was associated with more modular brain connectivity, and lower life meaning was associated with higher between-network connectivity. These findings advance our understanding of loneliness and life meaning as distinct, yet interdependent, features of sociality. The results highlight a potential role of the default network as a central hub, providing a putative neural mechanism for shifting between feelings of isolation and purpose.

PMID: 30924854 [PubMed - as supplied by publisher]

Egomotion-related visual areas respond to active leg movements.

Sat, 03/30/2019 - 21:31
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Egomotion-related visual areas respond to active leg movements.

Hum Brain Mapp. 2019 Mar 28;:

Authors: Serra C, Galletti C, Di Marco S, Fattori P, Galati G, Sulpizio V, Pitzalis S

Abstract
Monkey neurophysiology and human neuroimaging studies have demonstrated that passive viewing of optic flow stimuli activates a cortical network of temporal, parietal, insular, and cingulate visual motion regions. Here, we tested whether the human visual motion areas involved in processing optic flow signals simulating self-motion are also activated by active lower limb movements, and hence are likely involved in guiding human locomotion. To this aim, we used a combined approach of task-evoked activity and resting-state functional connectivity by fMRI. We localized a set of six egomotion-responsive visual areas (V6+, V3A, intraparietal motion/ventral intraparietal [IPSmot/VIP], cingulate sulcus visual area [CSv], posterior cingulate sulcus area [pCi], posterior insular cortex [PIC]) by using optic flow. We tested their response to a motor task implying long-range active leg movements. Results revealed that, among these visually defined areas, CSv, pCi, and PIC responded to leg movements (visuomotor areas), while V6+, V3A, and IPSmot/VIP did not (visual areas). Functional connectivity analysis showed that visuomotor areas are connected to the cingulate motor areas, the supplementary motor area, and notably to the medial portion of the somatosensory cortex, which represents legs and feet. We suggest that CSv, pCi, and PIC perform the visual analysis of egomotion-like signals to provide sensory information to the motor system with the aim of guiding locomotion.

PMID: 30924264 [PubMed - as supplied by publisher]

Cerebellar functional abnormalities in early stage drug-naïve and medicated Parkinson's disease.

Sat, 03/30/2019 - 21:31
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Cerebellar functional abnormalities in early stage drug-naïve and medicated Parkinson's disease.

J Neurol. 2019 Mar 28;:

Authors: Xu S, He XW, Zhao R, Chen W, Qin Z, Zhang J, Ban S, Li GF, Shi YH, Hu Y, Zhuang MT, Liu YS, Shen XL, Li J, Liu JR, Du X

Abstract
Parkinson's disease (PD) is a progressive neurological degenerative disorder characterized by impaired motor function and non-motor dysfunctions. While recent studies have highlighted the role of the cerebellum in PD, our understanding of its role in PD remains limited. In the present study, we used resting-state fMRI to evaluate dysfunctions within the cerebellum in PD patients treated with medication and drug-naïve PD patients. We applied amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) analysis methods. Thirty-one patients with early stage PD (22 drug-naïve and 9 medicated patients) and 31 gender- and age-matched healthy controls were recruited in this study. ALFFs increased in the left cerebellar areas (lobules VI/VIIb/CruI/CruII and the dentate gyrus) and right cerebellar areas (lobules VI/VIIb/VIIIa/CruI/CruII and the dentate gyrus) of all PD patients and in the left and right cerebellar areas (lobules VI/VIIb/CruI and the dentate gyrus) of drug-naive PD patients but were not significantly changed in medicated PD patients. DC increased in the right cerebellar areas of all PD patients and medicated PD patients. All PD patients and all drug-naive PD patients showed significantly weaker functional connectivity (FC) between the left cerebellum and the left medial frontal gyrus. However, FC was significantly stronger between the right cerebellum and the left precentral and right middle occipital gyri in the medicated PD patients than in controls. Furthermore, a correlation analyses revealed that ALFF z scores in the left cerebellum (lobule VI) and right cerebellum (lobule VI/CruI and dentate gyrus) were negatively correlated with Mini-Mental State Examination (MMSE) scores in all PD patients and drug-naive patients. These results indicate that the cerebellum plays an important role in PD, mainly by exerting a compensatory effect in early stage PD. Additionally, antiparkinsonian medication would modified PD-induced changes in local neural activity and FC in PD patients. The results of this study offer novel insights into the roles of the cerebellum in early stage drug-naïve PD.

PMID: 30923933 [PubMed - as supplied by publisher]

Optimizing BOLD sensitivity in the 7T Human Connectome Project resting-state fMRI protocol using plug-and-play parallel transmission.

Sat, 03/30/2019 - 21:31
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Optimizing BOLD sensitivity in the 7T Human Connectome Project resting-state fMRI protocol using plug-and-play parallel transmission.

Neuroimage. 2019 Mar 25;:

Authors: Gras V, Poser BA, Wu X, Tomi-Tricot R, Boulant N

Abstract
The Human Connectome Project (HCP) has a 7T component that aims to study the human brain's organization and function with high spatial and temporal resolution fMRI and diffusion-weighted acquisitions. For whole brain applications at 7T, a major weakness however remains the heterogeneity of the radiofrequency transmission field (B1+ ), which prevents from achieving an optimal signal and contrast homogeneously throughout the brain. In this work, we use parallel transmission (pTX) Universal Pulses (UP) to improve the flip angle homogeneity and demonstrate their application to highly accelerated multi-band EPI (MB5 and GRAPPA2, as prescribed in the 7T HCP protocol) sequence, but also to acquire at 7T B1+ -artefact-free T1 - and T2 -weighted anatomical scans used in the pre-processing pipeline of the HCP protocol. As compared to typical implementations of pTX, the proposed solution is fully operator-independent and allows "plug and play" exploitation of the benefits offered by multi-channel transmission. Validation in five healthy adults shows that the proposed technique achieves a flip angle homogeneity comparable to that of a clinical 3 T system. Compared to standard single-channel transmission, the use of UPs at 7T yielded up to a two-fold increase of the temporal signal-to-noise ratio in the temporal lobes as well as improved detection of functional connectivity in the brain regions most strongly affected by B1+ inhomogeneity.

PMID: 30923027 [PubMed - as supplied by publisher]

Resting state connectivity best predicts alcohol use severity in moderate to heavy alcohol users.

Fri, 03/29/2019 - 21:30
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Resting state connectivity best predicts alcohol use severity in moderate to heavy alcohol users.

Neuroimage Clin. 2019 Mar 19;22:101782

Authors: Fede SJ, Grodin EN, Dean SF, Diazgranados N, Momenan R

Abstract
BACKGROUND: In the United States, 13% of adults are estimated to have alcohol use disorder (AUD). Most studies examining the neurobiology of AUD treat individuals with this disorder as a homogeneous group; however, the theories of the neurocircuitry of AUD call for a quantitative and dimensional approach. Previous imaging studies find differences in brain structure, function, and resting-state connectivity in AUD, but few use a multimodal approach to understand the association between severity of alcohol use and the brain differences.
METHODS: Adults (ages 22-60) with problem drinking patterns (n = 59) completed a behavioral and neuroimaging protocol at the National Institutes of Health. Alcohol severity was quantified with the Alcohol Use Disorders Identification Test (AUDIT). In a 3 T MRI scanner, participants underwent a structural MRI as well as resting-state, monetary incentive delay, and face matching fMRI scans. Machine learning was applied and trained using the neural data from MRI scanning. The model was tested for generalizability in a validation sample (n = 24).
RESULTS: The resting state-connectivity features model best predicted AUD severity in the naïve sample, compared to task fMRI, structural MRI, combined MRI features, or demographic features. Network connectivity features between salience network, default mode network, executive control network, and sensory networks explained 33% of the variance associated with AUDIT in this model.
CONCLUSIONS: These findings indicate that the neural effects of AUD vary according to severity. Our results emphasize the utility of resting state fMRI as a neuroimaging biomarker for quantitative clinical evaluation of AUD.

PMID: 30921611 [PubMed - as supplied by publisher]

Group ICA for identifying biomarkers in schizophrenia: 'Adaptive' networks via spatially constrained ICA show more sensitivity to group differences than spatio-temporal regression.

Fri, 03/29/2019 - 21:30
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Group ICA for identifying biomarkers in schizophrenia: 'Adaptive' networks via spatially constrained ICA show more sensitivity to group differences than spatio-temporal regression.

Neuroimage Clin. 2019 Mar 05;22:101747

Authors: Salman MS, Du Y, Lin D, Fu Z, Fedorov A, Damaraju E, Sui J, Chen J, Mayer AR, Posse S, Mathalon DH, Ford JM, Van Erp T, Calhoun VD

Abstract
Brain functional networks identified from fMRI data can provide potential biomarkers for brain disorders. Group independent component analysis (GICA) is popular for extracting brain functional networks from multiple subjects. In GICA, different strategies exist for reconstructing subject-specific networks from the group-level networks. However, it is unknown whether these strategies have different sensitivities to group differences and abilities in distinguishing patients. Among GICA, spatio-temporal regression (STR) and spatially constrained ICA approaches such as group information guided ICA (GIG-ICA) can be used to propagate components (indicating networks) to a new subject that is not included in the original subjects. In this study, based on the same a priori network maps, we reconstructed subject-specific networks using these two methods separately from resting-state fMRI data of 151 schizophrenia patients (SZs) and 163 healthy controls (HCs). We investigated group differences in the estimated functional networks and the functional network connectivity (FNC) obtained by each method. The networks were also used as features in a cross-validated support vector machine (SVM) for classifying SZs and HCs. We selected features using different strategies to provide a comprehensive comparison between the two methods. GIG-ICA generally showed greater sensitivity in statistical analysis and better classification performance (accuracy 76.45 ± 8.9%, sensitivity 0.74 ± 0.11, specificity 0.79 ± 0.11) than STR (accuracy 67.45 ± 8.13%, sensitivity 0.65 ± 0.11, specificity 0.71 ± 0.11). Importantly, results were also consistent when applied to an independent dataset including 82 HCs and 82 SZs. Our work suggests that the functional networks estimated by GIG-ICA are more sensitive to group differences, and GIG-ICA is promising for identifying image-derived biomarkers of brain disease.

PMID: 30921608 [PubMed - as supplied by publisher]

The situation or the person? Individual and task-evoked differences in BOLD activity.

Fri, 03/29/2019 - 21:30

The situation or the person? Individual and task-evoked differences in BOLD activity.

Hum Brain Mapp. 2019 Mar 28;:

Authors: Bolt T, Nomi JS, Bainter SA, Cole MW, Uddin LQ

Abstract
Investigations of between-person variability are enjoying a recent resurgence in functional magnetic resonance imaging (fMRI) research. Several recent studies have found persistent between-person differences in blood-oxygenated-level dependent (BOLD) activation patterns and resting-state functional connectivity. Conflicting findings have been reported regarding the extent to which (a) between-person or (b) within-person cognitive state differences explain differences in BOLD activation patterns. These discrepancies may arise due to statistical analysis choices, parcellation resolution, and limited sampling of task-fMRI datasets. We attempt to address these issues in a large-scale analysis of several task-fMRI paradigms. Using a novel application of multivariate distance matrix regression, we examine between-person and task-condition variability estimates across varying levels of "resolution", from a coarse region-of-interest level to the vertex-level, and across different distance metrics. These analyses revealed that under most circumstances, differences in task conditions explained a greater amount of variance in activation map differences than between-person differences. However, this finding was reversed when comparing activation maps at a "high-resolution" vertex level. More generally, we observed that when moving from "low" to "high" resolutions, the variance explained by between-person differences increased while variance explained by task conditions decreased. We further analyzed the relationships among subject-level activation maps across all task-conditions using an unsupervised clustering approach and identified a superordinate task structure. This structure went beyond conventional task labels and highlighted those experimental manipulations across task conditions that produce contrasting versus similar whole-brain activation patterns. Overall, these analyses suggest that the question of the subject- versus task-effects on BOLD activation patterns is nontrivial, and depends on the comparison "resolution," choice of distance metric, and the coding of task-conditions.

PMID: 30919517 [PubMed - as supplied by publisher]

Neural correlates of cognitive control deficits in children with reading disorder.

Fri, 03/29/2019 - 21:30

Neural correlates of cognitive control deficits in children with reading disorder.

Brain Imaging Behav. 2019 Mar 28;:

Authors: Margolis AE, Pagliaccio D, Davis KS, Thomas L, Banker SM, Cyr M, Marsh R

Abstract
Reading disorder (RD) is characterized by deficient phonological processing, but children with RD also have cognitive control deficits, the neural correlates of which are not fully understood. We used fMRI to assess neural activity during the resolution of cognitive conflict on the Simon Spatial Incompatibility task and patterns of resting-state functional connectivity (RSFC) from task control (TC) regions in 7-12-year-old children with RD compared to their typically developing (TD) peers. Relative to TD children (n = 17), those with RD (n = 16) over-engaged a right superior/medial frontal cluster during the resolution of conflict (p = .05). Relative to TD children (n = 18), those with RD (n = 17) also showed reduced RSFC (voxel-wise p < .001; cluster-size p < .05, FDR corrected) from cingulo-opercular seeds to left hemisphere fronto-parietal and temporo-parietal reading-related regions, perhaps reflecting reduced organization of TC circuits and reduced integration with reading-related regions. Children with RD additionally showed reduced RSFC between fronto-parietal and default mode network regions. Follow-up analyses in a subset of children with both useable task and resting state data (RD = 13; TD = 17) revealed that greater conflict-related activation of the right frontal Simon task ROI associated with better word-reading, perhaps suggesting a compensatory role for this over-engagement. Connectivity from fronto-parietal seeds significantly associated with Simon task performance and word-reading accuracy in RD children. These findings suggest that altered functioning and connectivity of control circuits may contribute to cognitive control deficits in children with RD. Future studies should assess the utility of adding cognitive control training to reading remediation programs.

PMID: 30919230 [PubMed - as supplied by publisher]

Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia.

Fri, 03/29/2019 - 21:30

Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia.

Sci Rep. 2019 Mar 27;9(1):5283

Authors: Hosomi F, Yanagi M, Kawakubo Y, Tsujii N, Ozaki S, Shirakawa O

Abstract
Near-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.

PMID: 30918285 [PubMed - in process]

Top-down alteration of functional connectivity within the sensorimotor network in focal dystonia.

Fri, 03/29/2019 - 21:30
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Top-down alteration of functional connectivity within the sensorimotor network in focal dystonia.

Neurology. 2019 Mar 27;:

Authors: Battistella G, Simonyan K

Abstract
OBJECTIVES: To determine the directionality of regional interactions and influences of one region on another within the functionally abnormal sensorimotor network in isolated focal dystonia.
METHODS: A total of 40 patients with spasmodic dysphonia with and without dystonic tremor of voice and 35 healthy controls participated in the study. Independent component analysis (ICA) of resting-state fMRI was used to identify 4 abnormally coupled brain regions within the functional sensorimotor network in all patients compared to controls. Follow-up spectral dynamic causal modeling (DCM) estimated regional effective connectivity between patients and controls and between patients with spasmodic dysphonia with and without dystonic tremor of voice to expand the understanding of symptomatologic variability associated with this disorder.
RESULTS: ICA found abnormally reduced functional connectivity of the left inferior parietal cortex, putamen, and bilateral premotor cortex in all patients compared to controls, pointing to a largely overlapping pathophysiology of focal dystonia and dystonic tremor. DCM determined that the disruption of the sensorimotor network was both top-down, involving hyperexcitable parieto-putaminal influence, and interhemispheric, involving right-to-left hyperexcitable premotor coupling in all patients compared to controls. These regional alterations were associated with their abnormal self-inhibitory function when comparing patients with spasmodic dysphonia patients with and without dystonic tremor of voice.
CONCLUSIONS: Abnormal hyperexcitability of premotor-parietal-putaminal circuitry may be explained by altered information transfer between these regions due to underlying deficient connectivity. Identification of brain regions involved in processing of sensorimotor information in preparation for movement execution suggests that complex network disruption is staged well before the dystonic behavior is produced by the primary motor cortex.

PMID: 30918091 [PubMed - as supplied by publisher]

Functional networks are impaired by elevated tau-protein but reversible in a regulatable Alzheimer's disease mouse model.

Fri, 03/29/2019 - 21:30

Functional networks are impaired by elevated tau-protein but reversible in a regulatable Alzheimer's disease mouse model.

Mol Neurodegener. 2019 Mar 27;14(1):13

Authors: Green C, Sydow A, Vogel S, Anglada-Huguet M, Wiedermann D, Mandelkow E, Mandelkow EM, Hoehn M

Abstract
BACKGROUND: Aggregation of tau proteins is a distinct hallmark of tauopathies and has been a focus of research and clinical trials for Alzheimer's Disease. Recent reports have pointed towards a toxic effect of soluble or oligomeric tau in the spreading of tau pathology in Alzheimer's disease. Here we investigated the effects of expressing human tau repeat domain (tauRD) with pro- or anti-aggregant mutations in regulatable transgenic mouse models of Alzheimer's Disease on the functional neuronal networks and the structural connectivity strength.
METHODS: Pro-aggregant and anti-aggregant mice were studied when their mutant tauRD was switched on for 12 months to reach the stage where pro-aggregant mice show cognitive impairment, whereas anti-aggregant mice remained cognitively normal. Then, mutant tauRD was switched off by doxycycline treatment for 8 weeks so that soluble transgenic tau disappeared and cognition recovered in the pro-aggregant mice, although some aggregates remained. At these two time points, at baseline after 12 months of mutant tau expression and after 8 weeks of doxycycline treatment, resting state fMRI and diffusion MRI were used to determine functional neuronal networks and fiber connectivities. Results of the transgenic mice were compared with wildtype littermates.
RESULTS: Functional connectivity was strongly reduced in transgenic animals during mutant tauRD expression, in relation to WT mice. Interestingly, transgenic mice with the non-aggregant tau mutant showed identical functional deficits as the pro-aggregant mice, even though in this case there was no cognitive decline by behavioral testing. Upon 8 weeks doxycycline treatment and transgene switch-off, functional connectivity in both transgenic groups presented complete normalization of functional connectivity strength, equivalent to the situation in WT littermates. Structural connectivity was found only marginally sensitive to mutant tau expression (both pro- and anti-aggregant tauRD) and by doxycycline treatment.
CONCLUSIONS: Our in vivo investigations unravel for the first time a strong reduction of functional neuronal networks by the presence of increased soluble rather than fibrillary tau, independent of its intrinsic propensity of aggregation, which is reversible by switching tau off. Our functional MRI study thus is an unexpected in vivo validation of a novel property of tau, while previous results pointed to a role of aggregation propensity for a pathological state by histopathology and cognitive decline. Our results present further evidence for early tauopathy biomarkers or a potential early stage drug target by functional networks analysis.

PMID: 30917861 [PubMed - in process]

Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients.

Thu, 03/28/2019 - 18:30
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Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients.

Front Integr Neurosci. 2019;13:8

Authors: Narasimham S, McGovern EM, Quinlivan B, Killian O, Beck R, O'Riordan S, Hutchinson M, Reilly RB

Abstract
Background: An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms. Objective: To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD. Methods: Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses. Results: Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination. Conclusion: Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.

PMID: 30914929 [PubMed]

Somatosensory Stimulation With XNKQ Acupuncture Modulates Functional Connectivity of Motor Areas.

Thu, 03/28/2019 - 18:30
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Somatosensory Stimulation With XNKQ Acupuncture Modulates Functional Connectivity of Motor Areas.

Front Neurosci. 2019;13:147

Authors: Nierhaus T, Chang Y, Liu B, Shi X, Yi M, Witt CM, Pach D

Abstract
Xingnao Kaiqiao (XNKQ) acupuncture is an acupuncture technique used for stroke patients. In 24 healthy volunteers, we applied this complex acupuncture intervention, which consists of a manual needle-stimulation on five acupuncture points (DU26 unilaterally, PC6, and SP6 bilaterally). XNKQ was compared to three control conditions: (1) insertion of needles on the XNKQ acupuncture points without stimulation, (2) manual needle-stimulation on five nearby non-acupuncture points, and (3) insertion of needles on the non-acupuncture points without stimulation. In a within-subject design, we investigated functional connectivity changes in resting-state functional magnetic resonance imaging (fMRI) by means of the data-driven eigenvector centrality (EC) approach. With a 2 × 2 factorial within-subjects design with two-factor stimulation (stimulation vs. non-stimulation) and location (acupuncture points vs. non-acupuncture points), we found decreased EC in the precuneus after needle-stimulation (stimulation<non-stimulation), whereas the factor location showed no statistically significant EC differences. XNKQ acupuncture compared with needle-stimulation on non-acupuncture points showed decreased EC primarily in subcortical structures such as the caudate nucleus, subthalamic nucleus, and red nucleus. Post-hoc seed-based analysis revealed that the decrease in EC was mainly driven by reduced temporal correlation to primary sensorimotor cortices. The comparison of XNKQ acupuncture with the other two (non-stimulation) interventions showed no significant differences in EC. Our findings support the importance of the stimulation component of the acupuncture intervention and hint toward the modulation of functional connectivity by XNKQ acupuncture, especially in areas involved in motor function. As a next step, similar mechanisms should be validated in stroke patients suffering from motor deficits. ClinicalTrials.gov ID: NCT02453906.

PMID: 30914909 [PubMed]