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The periaqueductal gray and descending pain modulation: Why should we study them and what role do they play in chronic pain?

Sat, 02/14/2015 - 18:30

The periaqueductal gray and descending pain modulation: Why should we study them and what role do they play in chronic pain?

J Neurophysiol. 2015 Feb 11;:jn.00998.2014

Authors: Hemington KS, Coulombe MA

Abstract
Here, we discuss the significance of a recent study by Yu et al. (Neuroimage: Clinical 6: 100-108, 2014). The authors examined functional connectivity of a key node of the descending pain modulation pathway, the periaqueductal gray (PAG), in chronic back pain patients. Altered PAG connectivity to pain-related regions was found; we place results within the context of recent literature and emphasize the importance of understanding the descending component of pain in pain research.

PMID: 25673745 [PubMed - as supplied by publisher]

Modulation of cerebello-cerebral resting state networks by site specific stimulation.

Sat, 02/14/2015 - 18:30

Modulation of cerebello-cerebral resting state networks by site specific stimulation.

J Neurophysiol. 2015 Feb 11;:jn.00977.2014

Authors: Rastogi A, Ghahremani A, Cash RF

Abstract
Converging evidence from neuroimaging and neuromodulation literature suggests that the cerebellum plays a broad role in motor as well as cognitive processes through its participation in resting state networks. A recent study by Halko and colleagues (2014) demonstrates, for the first time, the ability to modulate functional connectivity of some of these distinct resting state networks using site-specific repetitive transcranial magnetic stimulation (rTMS) of the cerebellum. Here, we discuss and critically analyze this study, emphasizing important findings, potential therapeutic relevance, and areas worthy of further inquiry.

PMID: 25673743 [PubMed - as supplied by publisher]

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

Sat, 02/14/2015 - 18:30

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

Med Sci Monit. 2015;21:459-67

Authors: Liu WJ, Yin DZ, Cheng WH, Fan MX, You MN, Men WW, Zang LL, Shi DH, Zhang F

Abstract
Background We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). Material and Methods A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. Results Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. Conclusions Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways.

PMID: 25673008 [PubMed - in process]

Epilepsy and functional brain networks.

Sat, 02/14/2015 - 18:30

Epilepsy and functional brain networks.

Rinsho Shinkeigaku. 2014;54(12):1139-41

Authors: Uehara T, Shigeto H, Kira J

Abstract
Recent resting-state functional MRI (rs-fMRI) studies have demonstrated that the human brain is composed of several essential large-scale functional brain networks, including the "default-mode network". We analyzed electrocorticogram data from four patients with intractable focal epilepsy and compared the extent of these large-scale functional brain networks with propagation pathways of ictal discharge. We found that large-scale functional brain networks had markedly similar spatial patterns compared with multisite ictal fast activity, suggesting that some epileptic activity propagates along large-scale functional brain networks. Given that decreased functional connectivity in large-scale functional brain networks has been reported in patients with focal epilepsy, ictal propagation may lead to chronic alteration of normal functional networks in the brain.

PMID: 25672730 [PubMed - in process]

Amyloid and its association with default network integrity in Alzheimer's disease.

Sat, 02/14/2015 - 18:30
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Amyloid and its association with default network integrity in Alzheimer's disease.

Hum Brain Mapp. 2014 Mar;35(3):779-91

Authors: Adriaanse SM, Sanz-Arigita EJ, Binnewijzend MA, Ossenkoppele R, Tolboom N, van Assema DM, Wink AM, Boellaard R, Yaqub M, Windhorst AD, van der Flier WM, Scheltens P, Lammertsma AA, Rombouts SA, Barkhof F, van Berckel BN

Abstract
The purpose of this study was to investigate the association between functional connectivity and β-amyloid depositions in the default mode network (DMN) in Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy elderly. Twenty-five patients with AD, 12 patients with MCI, and 18 healthy controls were included in the study. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in the DMN. In parallel, amyloid burden was measured in the same subjects using positron emission tomography with carbon-11-labeled Pittsburgh Compound-B as amyloid tracer. Functional connectivity of the DMN and amyloid deposition within the DMN were not associated across all subjects or within diagnostic groups. Longitudinal studies are needed to examine if amyloid depositions precede aberrant functional connectivity in the DMN.

PMID: 23238869 [PubMed - indexed for MEDLINE]

Causal manipulation of functional connectivity in a specific neural pathway during behaviour and at rest.

Fri, 02/13/2015 - 16:30
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Causal manipulation of functional connectivity in a specific neural pathway during behaviour and at rest.

Elife. 2015 Feb 9;4

Authors: Johnen VM, Neubert FX, Buch ER, Verhagen LM, O'Reilly J, Mars RB, Rushworth MF

Abstract
Correlations in brain activity between two areas (functional connectivity) have been shown to relate to their underlying structural connections. We examine the possibility that functional connectivity also reflects short-term changes in synaptic efficacy. We demonstrate that paired transcranial magnetic stimulation (TMS) near ventral premotor cortex (PMv) and primary motor cortex (M1) with a short 8ms inter-pulse interval evoking synchronous pre- and post-synaptic activity and which strengthens interregional connectivity between the two areas in a pattern consistent with Hebbian plasticity, leads to increased functional connectivity between PMv and M1 as measured with functional magnetic resonance imaging (fMRI). Moreover, we show that strengthening connectivity between these nodes has effects on a wider network of areas, such as decreasing coupling in a parallel motor programming stream. A control experiment revealed that identical TMS pulses at identical frequencies caused no change in fMRI-measured functional connectivity when the inter-pulse-interval was too long for Hebbian-like plasticity.

PMID: 25664941 [PubMed - as supplied by publisher]

Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM.

Fri, 02/13/2015 - 16:30
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Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM.

Hum Brain Mapp. 2015 Feb 9;

Authors: Dyrba M, Grothe M, Kirste T, Teipel SJ

Abstract
Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph-theoretical measures 'local clustering coefficient' and 'shortest path length' derived from resting-state functional MRI (rs-fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave-one-out cross-validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs-fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

PMID: 25664619 [PubMed - as supplied by publisher]

Introducing co-activation pattern metrics to quantify spontaneous brain network dynamics.

Fri, 02/13/2015 - 16:30
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Introducing co-activation pattern metrics to quantify spontaneous brain network dynamics.

Neuroimage. 2015 Feb 6;

Authors: Chen JE, Chang C, Greicius MD, Glover GH

Abstract
Recently, fMRI researchers have begun to realize that the brain's intrinsic network patterns may undergo substantial changes during a single resting state (RS) scan. However, despite the growing interest in brain dynamics, metrics that can quantify the variability of network patterns are still quite limited. Here, we first introduce various quantification metrics based on the extension of co-activation pattern (CAP) analysis, a recently proposed point-process analysis that tracks state alternations at each individual time frame and relies on very few assumptions; then apply these proposed metrics to quantify changes of brain dynamics during a sustained 2-back working memory (WM) task compared to rest. We focus on the functional connectivity of two prominent RS networks, the default-mode network (DMN) and executive control network (ECN). We first demonstrate less variability of global Pearson correlations with respect to the two chosen networks using a sliding-window approach during WM task compared to rest; then we show that the macroscopic decrease in variations in correlations during a WM task is also well characterized by the combined effect of a reduced number of dominant CAPs, increased spatial consistency across CAPs, and increased fractional contributions of a few dominant CAPs. These CAP metrics may provide alternative and more straightforward quantitative means of characterizing brain network dynamics than time-windowed correlation analyses.

PMID: 25662866 [PubMed - as supplied by publisher]

The neurological underpinnings of cluttering: Some initial findings.

Fri, 02/13/2015 - 16:30
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The neurological underpinnings of cluttering: Some initial findings.

J Fluency Disord. 2015 Jan 8;

Authors: Ward D, Connally EL, Pliatsikas C, Bretherton-Furness J, Watkins KE

Abstract
BACKGROUND: Cluttering is a fluency disorder characterised by overly rapid or jerky speech patterns that compromise intelligibility. The neural correlates of cluttering are unknown but theoretical accounts implicate the basal ganglia and medial prefrontal cortex. Dysfunction in these brain areas would be consistent with difficulties in selection and control of speech motor programs that are characteristic of speech disfluencies in cluttering. There is a surprising lack of investigation into this disorder using modern imaging techniques. Here, we used functional MRI to investigate the neural correlates of cluttering.
METHOD: We scanned 17 adults who clutter and 17 normally fluent control speakers matched for age and sex. Brain activity was recorded using sparse-sampling functional MRI while participants viewed scenes and either (i) produced overt speech describing the scene or (ii) read out loud a sentence provided that described the scene. Speech was recorded and analysed off line. Differences in brain activity for each condition compared to a silent resting baseline and between conditions were analysed for each group separately (cluster-forming threshold Z>3.1, extent p<0.05, corrected) and then these differences were further compared between the two groups (voxel threshold p<0.01, extent>30 voxels, uncorrected).
RESULTS: In both conditions, the patterns of activation in adults who clutter and control speakers were strikingly similar, particularly at the cortical level. Direct group comparisons revealed greater activity in adults who clutter compared to control speakers in the lateral premotor cortex bilaterally and, as predicted, on the medial surface (pre-supplementary motor area). Subcortically, adults who clutter showed greater activity than control speakers in the basal ganglia. Specifically, the caudate nucleus and putamen were overactive in adults who clutter for the comparison of picture description with sentence reading. In addition, adults who clutter had reduced activity relative to control speakers in the lateral anterior cerebellum bilaterally. Eleven of the 17 adults who clutter also stuttered. This comorbid diagnosis of stuttering was found to contribute to the abnormal overactivity seen in the group of adults who clutter in the right ventral premotor cortex and right anterior cingulate cortex. In the remaining areas of abnormal activity seen in adults who clutter compared to controls, the subgroup who clutter and stutter did not differ from the subgroup who clutter but do not stutter.
CONCLUSIONS: Our findings were in good agreement with theoretical predictions regarding the neural correlates of cluttering. We found evidence for abnormal function in the basal ganglia and their cortical output target, the medial prefrontal cortex. The findings are discussed in relation to models of cluttering that point to problems with motor control of speech. Educational objectives: This paper reports findings on the neural correlates seen in adults who clutter, and offers hypotheses as to how these might map onto the behaviours seen amongst those who clutter. Readers will be able to (a) identify the structures that are implicated in the disorder of cluttering, (b) understand arguments relating these structures to the behavioural expression of the disorder, (c) understand some of the complexities in interpreting data pertaining to recovery from cluttering, (d) understand where future efforts in research into the neurological correlates of cluttering should be focussed.

PMID: 25662409 [PubMed - as supplied by publisher]

In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.

Fri, 02/13/2015 - 16:30
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In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.

Brain Connect. 2014 Jun;4(5):371-83

Authors: Klupp E, Förster S, Grimmer T, Tahmasian M, Yakushev I, Sorg C, Yousefi BH, Drzezga A

Abstract
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 a consequence of local amyloid toxicity. The aim of this multimodal imaging study was to explore whether such HO phenomenon may be related to pathologies in functionally connected, remote brain regions. Nineteen AD patients and 15 matched controls underwent examinations with [(11)C]PiB-PET and [(18)F]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 a seed region for a functional connectivity analysis in resting-state functional magnetic resonance imaging 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 positron emission tomography (PET) datasets. The most prominent HO area was detected in the left middle frontal gyrus of AD patients. The HO-ICN in healthy controls showed a major overlap with brain areas significantly affected by both amyloid deposition and hypometabolism in patients. This association was substantiated by the results of region-of-interest-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 ongoing pathologies in remote but functionally connected regions, that is, by reduced neuronal input from these regions.

PMID: 24870443 [PubMed - indexed for MEDLINE]

Changes in whole-brain functional networks and memory performance in aging.

Fri, 02/13/2015 - 16:30
Related Articles

Changes in whole-brain functional networks and memory performance in aging.

Neurobiol Aging. 2014 Oct;35(10):2193-202

Authors: Sala-Llonch R, Junqué C, Arenaza-Urquijo EM, Vidal-Piñeiro D, Valls-Pedret C, Palacios EM, Domènech S, Salvà A, Bargalló N, Bartrés-Faz D

Abstract
We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance.

PMID: 24814675 [PubMed - indexed for MEDLINE]

Disrupted Resting-State Functional Connectivity in Progressive Supranuclear Palsy.

Wed, 02/11/2015 - 13:30

Disrupted Resting-State Functional Connectivity in Progressive Supranuclear Palsy.

AJNR Am J Neuroradiol. 2015 Feb 5;

Authors: Piattella MC, Tona F, Bologna M, Sbardella E, Formica A, Petsas N, Filippini N, Berardelli A, Pantano P

Abstract
BACKGROUND AND PURPOSE: Studies on functional connectivity in progressive supranuclear palsy have been restricted to the thalamus and midbrain tegmentum. The present study aims to evaluate functional connectivity abnormalities of the subcortical structures in these patients. Functional connectivity will be correlated with motor and nonmotor symptoms of the disease.
MATERIALS AND METHODS: Nineteen patients with progressive supranuclear palsy (mean age, 70.93 ± 5.19 years) and 12 age-matched healthy subjects (mean age, 69.17 ± 5.20 years) underwent multimodal MR imaging, including fMRI at rest, 3D T1-weighted imaging, and DTI. fMRI data were processed with fMRI of the Brain Software Library tools by using the dorsal midbrain tegmentum, thalamus, caudate nucleus, putamen, and pallidum as seed regions.
RESULTS: Patients had lower functional connectivity than healthy subjects in all 5 resting-state networks, mainly involving the basal ganglia, thalamus, anterior cingulate, dorsolateral prefrontal and temporo-occipital cortices, supramarginal gyrus, supplementary motor area, and cerebellum. Compared with healthy subjects, patients also displayed subcortical atrophy and DTI abnormalities. Decreased thalamic functional connectivity correlated with clinical scores, as assessed by the Hoehn and Yahr Scale and by the bulbar and mentation subitems of the Progressive Supranuclear Palsy Rating Scale. Decreased pallidum functional connectivity correlated with lower Mini-Mental State Examination scores; decreased functional connectivity in the dorsal midbrain tegmentum network correlated with lower scores in the Frontal Assessment Battery.
CONCLUSIONS: The present study demonstrates a widespread disruption of cortical-subcortical connectivity in progressive supranuclear palsy and provides further insight into the pathophysiologic mechanisms of motor and cognitive impairment in this condition.

PMID: 25655870 [PubMed - as supplied by publisher]

Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age.

Wed, 02/11/2015 - 13:30
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Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age.

Neuroimage. 2014 Aug 15;97:321-32

Authors: Li CS, Ide JS, Zhang S, Hu S, Chao HH, Zaborszky L

Abstract
The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.

PMID: 24736176 [PubMed - indexed for MEDLINE]

Classifying the wandering mind: revealing the affective content of thoughts during task-free rest periods.

Wed, 02/11/2015 - 13:30
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Classifying the wandering mind: revealing the affective content of thoughts during task-free rest periods.

Neuroimage. 2014 Aug 15;97:107-16

Authors: Tusche A, Smallwood J, Bernhardt BC, Singer T

Abstract
Many powerful human emotional thoughts are generated in the absence of a precipitating event in the environment. Here, we tested whether we can decode the valence of internally driven, self-generated thoughts during task-free rest based on neural similarities with task-related affective mental states. We acquired functional magnetic resonance imaging (fMRI) data while participants generated positive and negative thoughts as part of an attribution task (Session A) and while they reported the occurrence of comparable mental states during task-free rest periods (Session B). With the use of multivariate pattern analyses (MVPA), we identified response patterns in the medial orbitofrontal cortex (mOFC) that encode the affective content of thoughts that are generated in response to an external experimental cue. Importantly, these task driven response patterns reliably predicted the occurrence of affective thoughts generated during unconstrained rest periods recorded one week apart. This demonstrates that at least certain elements of task-cued and task-free affective experiences rely on a common neural code. Furthermore, our findings reveal the role that the mOFC plays in determining the affective tone of unconstrained thoughts. More generally, our results suggest that MVPA is an important methodological tool for attempts to understand unguided subject driven mental states such as mind-wandering and daydreaming based on neural similarities with task-based experiences.

PMID: 24705200 [PubMed - indexed for MEDLINE]

Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.

Wed, 02/11/2015 - 13:30
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Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.

Neuroimage. 2014 Jul 1;94:385-95

Authors: Gamboa OL, Tagliazucchi E, von Wegner F, Jurcoane A, Wahl M, Laufs H, Ziemann U

Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disorder of the central nervous system characterized by multifocal white matter brain lesions leading to alterations in connectivity at the subcortical and cortical level. Graph theory, in combination with neuroimaging techniques, has been recently developed into a powerful tool to assess the large-scale structure of brain functional connectivity. Considering the structural damage present in the brain of MS patients, we hypothesized that the topological properties of resting-state functional networks of early MS patients would be re-arranged in order to limit the impact of disease expression. A standardized dual task (Paced Auditory Serial Addition Task simultaneously performed with a paper and pencil task) was administered to study the interactions between behavioral performance and functional network re-organization. We studied a group of 16 early MS patients (35.3±8.3 years, 11 females) and 20 healthy controls (29.9±7.0 years, 10 females) and found that brain resting-state networks of the MS patients displayed increased network modularity, i.e. diminished functional integration between separate functional modules. Modularity correlated negatively with dual task performance in the MS patients. Our results shed light on how localized anatomical connectivity damage can globally impact brain functional connectivity and how these alterations can impair behavioral performance. Finally, given the early stage of the MS patients included in this study, network modularity could be considered a promising biomarker for detection of earliest-stage brain network reorganization, and possibly of disease progression.

PMID: 24361662 [PubMed - indexed for MEDLINE]

Impact of hematocrit on measurements of the intrinsic brain.

Sat, 02/07/2015 - 13:30

Impact of hematocrit on measurements of the intrinsic brain.

Front Neurosci. 2014;8:452

Authors: Yang Z, Craddock RC, Milham MP

Abstract
Blood oxygenation level dependent (BOLD)-based functional MRI (fMRI) is a widely utilized neuroimaging technique for mapping brain function. Hematocrit (HCT), a global hematologic marker of the amount of hemoglobin in blood, is known to impact task-evoked BOLD activation. Yet, its impact on resting-state fMRI (R-fMRI) measures has not been characterized. We address this gap by testing for associations between HCT level and inter-individual variation in commonly employed R-fMRI indices of intrinsic brain function from 45 healthy adults. Given known sex differences in HCT, we also examined potential sex differences. Variation in baseline HCT among individuals were associated with regional differences in four of the six intrinsic brain indices examined. Portions of the default (anterior cingulate cortex/medial prefrontal cortex: ACC/MPFC), dorsal attention (intraparietal sulcus), and salience (insular and opercular cortex) network showed relationships with HCT for two measures. The relationships within MPFC, as well as visual and cerebellar networks, were modulated by sex. These results suggest that inter-individual variations in HCT can serve as a source of variations in R-fMRI derivatives at a regional level. Future work is needed to delineate whether this association is attributable to neural or non-neuronal source of variations and whether these effects are related to acute or chronic differences in HCT level.

PMID: 25653582 [PubMed]

Comparing interventions and exploring neural mechanisms of exercise in Parkinson disease: a study protocol for a randomized controlled trial.

Sat, 02/07/2015 - 13:30

Comparing interventions and exploring neural mechanisms of exercise in Parkinson disease: a study protocol for a randomized controlled trial.

BMC Neurol. 2015 Feb 5;15(1):9

Authors: Earhart GM, Duncan RP, Huang JL, Perlmutter JS, Pickett KA

Abstract
BackgroundEffective treatment of locomotor dysfunction in Parkinson disease (PD) is essential, as gait difficulty is an early and major contributor to disability. Exercise is recommended as an adjunct to traditional treatments for improving gait, balance, and quality of life. Among the exercise approaches known to improve walking, tango and treadmill training have recently emerged as two promising therapies for improving gait, disease severity and quality of life, yet these two interventions have not been directly compared to each other. Prior studies have been helpful in identifying interventions effective in improving gait function, but have done little to elucidate the neural mechanisms underlying functional improvements. The primary objective of the proposed work is to compare the effects of three community-based exercise programs, tango, treadmill training and stretching, on locomotor function in individuals with PD. In addition, we aim to determine whether and how these interventions alter functional connectivity of locomotor control networks in the brain.Methods/DesignOne hundred and twenty right-handed individuals with idiopathic PD who are at least 30 years of age will be assigned in successive waves to one of three community-based exercise groups: tango dancing, treadmill training or stretching (control). Each group will receive three months of exercise training with twice weekly one-hour group classes. Each participant will be evaluated at three time points: pre-intervention (baseline), post-intervention (3 months), and follow-up (6 months). All evaluations will include assessment of gait, balance, disease severity, and quality of life. Baseline and post-intervention evaluations will also include task-based functional magnetic resonance imaging (fMRI) and resting state functional connectivity MRI. All MRI and behavioral measures will be conducted with participants OFF anti-Parkinson medication, with behavioral measures also assessed ON medication.DiscussionThis study will provide important insights regarding the effects of different modes of exercise on locomotor function in PD. The protocol is innovative because it: 1) uses group exercise approaches for all conditions including treadmill training, 2) directly compares tango to treadmill training and stretching, 3) tests participants OFF medication, and 4) utilizes two distinct neuroimaging approaches to explore mechanisms of the effects of exercise on the brain.Trial registrationClinicalTrials.gov NCT01768832.

PMID: 25652002 [PubMed - as supplied by publisher]

Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment.

Fri, 02/06/2015 - 18:30

Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment.

Hum Brain Mapp. 2015 Feb 3;

Authors: Čeko M, Shir Y, Ouellet JA, Ware MA, Stone LS, Seminowicz DA

Abstract
We previously reported that effective treatment of chronic low back pain (CLBP) reversed abnormal brain structure and functional MRI (fMRI) activity during cognitive task performance, particularly in the left dorsolateral prefrontal cortex (DLPFC). Here, we used resting-state fMRI to examine how chronic pain affects connectivity of brain networks supporting cognitive functioning and the effect of treatment in 14 CLBP patients and 16 healthy, pain-free controls (scans were acquired at baseline for all subjects and at 6-months post-treatment for patients and a matched time-point for 10 controls). The main networks activated during cognitive task performance, task-positive network (TPN) and task-negative network (TNN) (aka default mode) network, were identified in subjects' task fMRI data and used to define matching networks in resting-state data. The connectivity of these cognitive resting-state networks was compared between groups, and before and after treatment. Our findings converged on the bilateral insula (INS) as the region of aberrant cognitive resting-state connectivity in patients pretreatment versus controls. These findings were complemented by an independent, data-driven approach showing altered global connectivity of the INS. Detailed investigation of the INS confirmed reduced connectivity to widespread TPN and TNN areas, which was partially restored post-treatment. Furthermore, analysis of diffusion-tensor imaging (DTI) data revealed structural changes in white matter supporting these findings. The left DLPFC also showed aberrant connectivity that was restored post-treatment. Altogether, our findings implicate the bilateral INS and left DLPFC as key nodes of disrupted cognition-related intrinsic connectivity in CLBP, and the resulting imbalance between TPN and TNN function is partially restored with treatment. Hum Brain Mapp, 2015. © 2014 Wiley Periodicals, Inc.

PMID: 25648842 [PubMed - as supplied by publisher]

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

Thu, 02/05/2015 - 16:30

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

Brain Connect. 2015 Feb 3;

Authors: Song J, Nair VA, Gaggl W, Prabhakaran V

Abstract
Objective: The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. Methods: A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network and individual brain regions. Results: At the whole brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (albeit weakly connected). At the functional network level, there were significant proportions of newly-formed connections between the default mode network and other networks, and between subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task-control network and other networks. Individual brain regions from different functional networks, however, showed distinct pattern of reorganizational changes in epilepsy. Significance: These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole brain level yet alters brain functional networks and individual brain regions differently.

PMID: 25647011 [PubMed - as supplied by publisher]

Nicotine and Resting State Functional Connectivity: Effects of Intermittent Doses.

Thu, 02/05/2015 - 16:30

Nicotine and Resting State Functional Connectivity: Effects of Intermittent Doses.

Nicotine Tob Res. 2015 Feb 2;

Authors: Huang W, Tam K, Fernando J, Heffernan M, King J, DiFranza JR

Abstract
INTRODUCTION: It is unknown how the timing between doses might affect nicotine's impact on neural activity. Our objective was to examine how the inter-dose interval affects nicotine's impact on resting state functional connectivity (rsFC).
METHODS: Adult male Sprague-Dawley rats were administered nicotine daily (0.4mg/kg) over 6 days while control animals received saline vehicle. Functional magnetic resonance imaging (fMRI) was used to measure rsFC before and after a challenge dose of nicotine (0.4mg/kg) delivered for the first time, and 3, 6, 12 or 24 Hrs after previous dose.
RESULTS: As the interval between nicotine doses increased from 3 to 24 Hrs, the strength of rsFC increased in some circuits, particularly the nucleus accumbens and prefrontal circuits, and decreased in others, namely the interpecuncular nucleus, hippocampus, caudoputamen, retrosplenial cortex, ventral tegmental, and the insular circuits.
CONCLUSIONS: These data indicate that the effect that nicotine has on the brain is affected by the amount of time that has passed since the previous dose. The effect on rsFC of cumulative doses is not additive. This may have important implications for the study of nicotine addiction as it implies that the same dose of nicotine might have a different impact on the brain depending on the time elapsed from the previous exposure.

PMID: 25646348 [PubMed - as supplied by publisher]