Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers

Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.

Towards the computer-aided diagnosis of dementia based on the geometric and network connectivity of structural MRI data

We present an intuitive geometric approach for analysing the structure and fragility of T1-weighted structural MRI scans of human brains. Apart from computing characteristics like the surface area and volume of regions of the brain that consist of highly active voxels, we also employ Network Theory in order to test how close these regions are to breaking apart. This analysis is used in an attempt to automatically classify subjects into three categories: Alzheimer’s disease, mild cognitive impairment and healthy controls, for the CADDementia Challenge.

Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using noninvasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (N30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2- dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25–90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial

Rationale: There has recently been increasing interest in the potential of flavanols, plant derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus stimulating neuronal function. Objectives: The present study employed arterial spin labelling (ASL) functional magnetic resonance imaging (FMRI) to explore the effect of a single acute dose of cocoa flavanols on regional CBF. Methods: CBF was measured pre and post consumption of low (23mg) or high (494mg) 330ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomised counterbalanced crossover double-blind design in eight males and ten females, aged 50-65 years. Changes in perfusion from pre to post consumption were calculated as a function of each drink. Results: Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex (ACC) and the central opercular cortex of the parietal lobe. Conclusions: Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance.

Landscape connectivity: a key to effective habitat restoration in lowland agricultural landscapes

Landscape scale habitat restoration has the potential to reconnect habitats in fragmented landscapes. This study investigates landscape connectivity as a key to effective habitat restoration in lowland agricultural landscapes and applies these findings to transferable management recommendations. The study area is the Stonehenge World Heritage Site, UK, where landscape scale chalk grassland restoration has been implemented. Here, the ecological benefits of landscape restoration and the species, habitat and landscape characteristics that facilitate or impede the enhancement of biodiversity and landscape connectivity were investigated. Lepidoptera were used as indictors of restoration success and results showed restoration grasslands approaching the ecological conditions of the target chalk grassland habitat and increasing in biodiversity values within a decade. Restoration success is apparent for four species with a broad range of grass larval host plants (e.g. Melanargia galathea, Maniola jurtina) or with intermediate mobility (Polyommatus icarus). However, two species with specialist larval host plants and low mobility (Lysandra bellargus), are restricted to chalk grassland fragments. Studies of restoration grassland of different ages show that recent grassland restoration (1 or 2 years old) may reduce the functional isolation of chalk grassland fragments. A management experiment showed that mowing increases boundary following behaviour in two species of grassland Lepidoptera; Maniola jurtina and Zygaena filipendulae. Analysis of the landscape scale implications of the grassland restoration illustrates an increase in grassland habitat network size and in landscape connectivity, which is likely to benefit the majority of grassland associated Lepidoptera. Landscape and habitat variables can be managed to increase the success of restoration projects including the spatial targeting of receptor sites, vegetation structure and selection of seed source and management recommendations are provided that are transferrable to other species-rich grassland landscape scale restoration projects. Overall results show restoration success for some habitats and species within a decade. However, additional management is required to assist the re-colonisation of specialist species. Despite this, habitat restoration at the landscape scale can be an effective, long term approach to enhance butterfly biodiversity and landscape connectivity.

Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay

In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC

Resting-state functional connectivity following a single dose treatment with CB1 neutral antagonist tetrahydrocannabivarin (THCv) in healthy volunteers

BACKGROUND: The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. METHOD: We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. RESULTS: Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. CONCLUSION: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.

Connectivity-based parcellation of the human frontal polar cortex

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity.

Connectivity recovery in epidemic membership protocols

Epidemic protocols are a bio-inspired communication and computation paradigm for extreme-scale network system based on randomized communication. The protocols rely on a membership service to build decentralized and random overlay topologies. In a weakly connected overlay topology, a naive mechanism of membership protocols can break the connectivity, thus impairing the accuracy of the application. This work investigates the factors in membership protocols that cause the loss of global connectivity and introduces the first topology connectivity recovery mechanism. The mechanism is integrated into the Expander Membership Protocol, which is then evaluated against other membership protocols. The analysis shows that the proposed connectivity recovery mechanism is effective in preserving topology connectivity and also helps to improve the application performance in terms of convergence speed.

Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults

The ability to regulate emotion is crucial to promote well-being. Evidence suggests that the medial prefrontal cortex (mPFC) and adjacent anterior cingulate (ACC) modulate amygdala activity during emotion regulation. Yet less is known about whether the amygdala-mPFC circuit is linked with regulation of the autonomic nervous system and whether the relationship differs across the adult lifespan. The current study tested the hypothesis that heart rate variability (HRV) reflects the strength of mPFC-amygdala interaction across younger and older adults. We recorded participants’ heart rates at baseline and examined whether baseline HRV was associated with amygdala-mPFC functional connectivity during rest. We found that higher HRV was associated with stronger functional connectivity between the amygdala and the mPFC during rest across younger and older adults. In addition to this age-invariant pattern, there was an age-related change, such that greater HRV was linked with stronger functional connectivity between amygdala and ventrolateral PFC (vlPFC) in younger than in older adults. These results are in line with past evidence that vlPFC is involved in emotion regulation especially in younger adults. Taken together, our results support the neurovisceral integration model and suggest that higher heart rate variability is associated with neural mechanisms that support successful emotional regulation across the adult lifespan.

Untreated dental caries in children with cerebral palsy in the Brazilian context

Objectives. To assess the prevalence of untreated dental caries in children with cerebral palsy and to assess socio-demographic, behavioural, and clinical covariates. Design. Cross-sectional assessment of 200 children and adolescents with cerebral palsy (2-17 years old) enrolled in a specialized healthcare unit in Sao Paulo, Brazil. The dental examination followed the World Health Organization`s guidelines for oral health surveys; familial caretakers informed on socio-economic status and behaviour; the patient`s medical record informed their clinical status. Results. The proportion of children that presented at least one tooth affected by untreated caries was 49.5%. Poor socio-economic standings and a higher frequency of sugar consumption associated with a worse profile of dental health; different types of cerebral palsy (spastic, tetraparesis) did not. The prevalence of untreated caries was higher than reference values assessed for the overall population of the same age range. Conclusions. The high burden of untreated dental caries on cerebral palsy patients reinforces the importance of the dentist in the interdisciplinary healthcare team attending these children. Factors associated with this outcome are the same for the general population; these findings underscore the necessity of implementing effective caries prevention in this population of cerebral palsy children.

Habitat fragmentation reduces genetic diversity and connectivity among toad populations in the Brazilian Atlantic Coastal Forest

Tropical rainforests are becoming increasingly fragmented and understanding the genetic consequences of fragmentation is crucial for conservation of their flora and fauna. We examined populations of the toad Rhinella ornata, a species endemic to Atlantic Coastal Forest in Brazil, and compared genetic diversity among small and medium forest fragments that were either isolated or connected to large forest areas by corridors. Genetic differentiation, as measured by F(ST), was not related to geographic distance among study sites and the size of the fragments did not significantly alter patterns of genetic connectivity. However, population genetic diversity was positively related to fragment size, thus haplotype diversity was lowest in the smallest fragments, likely due to decreases in population sizes. Spatial analyses of genetic discontinuities among groups of populations showed a higher proportion of barriers to gene flow among small and medium fragments than between populations in continuous forest. Our results underscore that even species with relatively high dispersal capacities may, over time, suffer the negative genetic effects of fragmentation, possibly leading to reduced fitness of population and cases of localized extinction. (C) 2008 Elsevier Ltd. All rights reserved.

Using gap-crossing capacity to evaluate functional connectivity of two Atlantic rainforest birds and their response to fragmentation

One of the main consequences of habitat loss and fragmentation is the increase in patch isolation and the consequent decrease in landscape connectivity. In this context, species persistence depends on their responses to this new landscape configuration, particularly on their capacity to move through the interhabitat matrix. Here, we aimed first to determine gap-crossing probabilities related to different gap widths for two forest birds (Thamnophilus caerulescens, Thamnophilidae, and Basileuterus culicivorus, Parulidae) from the Brazilian Atlantic rainforest. These values were defined with a playback technique and then used in analyses based on graph theory to determine functional connections among forest patches. Both species were capable of crossing forest gaps between patches, and these movements were related to gap width. The probability of crossing 40 m gaps was 50% for both species. This probability falls to 10% when the gaps are 60 m (for B. culicivorus) or 80 m (for T caerulescens). Actually, birds responded to stimulation about two times more distant inside forest trials (control) than in gap-crossing trials. Models that included gap-crossing capacity improved the explanatory power of species abundance variation in comparison to strictly structural models based merely on patch area and distance measurements. These results highlighted that even very simple functional connectivity measurements related to gap-crossing capacity can improve the understanding of the effect of habitat fragmentation on bird occurrence and abundance.