Neurofunctional Abnormalities during Sustained Attention in Severe Childhood Abuse

<div><p>Childhood maltreatment is associated with adverse affective and cognitive consequences including impaired emotion processing, inhibition and attention. However, the majority of functional magnetic resonance imaging (fMRI) studies in childhood maltreatment have examined emotion processing, while very few studies have tested the neurofunctional substrates of cognitive functions and none of attention. This study investigated the association between severe childhood abuse and fMRI brain activation during a parametric sustained attention task with a progressively increasing load of sustained attention in 21 medication-naïve, drug-free young people with a history of childhood abuse controlling for psychiatric comorbidities by including 19 psychiatric controls matched for psychiatric diagnoses, and 27 healthy controls. Behaviorally, the participants exposed to childhood abuse showed increased omission errors in the task which correlated positively trend-wise with the duration of their abuse. Neurofunctionally, the participants with a history of childhood abuse, but not the psychiatric controls, displayed significantly reduced activation relative to the healthy controls during the most challenging attention condition only in typical attention regions including left inferior and dorsolateral prefrontal cortex, insula and temporal areas. We therefore show for the first time that severe childhood abuse is associated with neurofunctional abnormalities in key ventral frontal-temporal sustained attention regions. The findings represent a first step towards the delineation of abuse-related neurofunctional abnormalities in sustained attention, which may help in the development of effective treatments for victims of childhood abuse.</p></div

Gliding motility of Plasmodium merozoites

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways

Gliding motility of Plasmodium merozoites.

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways

Heschl's gyrus is more sensitive to tone level than non-primary auditory cortex

Previous neuroimaging studies generally demonstrate a growth in the cortical response with an increase in sound level. However, the details of the shape and topographic location of such growth remain largely unknown. One limiting methodological factor has been the relatively sparse sampling of sound intensities. Additionally, most studies have either analysed the entire auditory cortex without differentiating primary and non-primary regions or have limited their analyses to Heschl's gyrus (HG). Here, we characterise the pattern of responses to a 300-Hz tone presented in 6-dB steps from 42 to 96 dB sound pressure level as a function of its sound level, within three anatomically defined auditory areas; the primary area, on HG, and two non-primary areas, consisting of a small area lateral to the axis of HG (the anterior lateral area, ALA) and the posterior part of auditory cortex (the planum temporale, PT). Extent and magnitude of auditory activation increased non-linearly with sound level. In HG, the extent and magnitude were more sensitive to increasing level than in ALA and PT. Thus, HG appears to have a larger involvement in sound-level processing than does ALA or PT

Neuroimaging of child abuse: a critical review

Childhood maltreatment is a severe stressor that can lead to the development of behaviour problems and affect brain structure and function. This review summarizes the current evidence for the effects of early childhood maltreatment on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest an association between child abuse and deficits in IQ, memory, executive function and emotion discrimination. Structural neuroimaging studies provide evidence for deficits in brain volume, grey and white matter of several regions, most prominently the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus callosum. Diffusion tensor imaging studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during executive function and emotion processing. There are, however, several limitations of the abuse research literature which are discussed, most prominently the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, the associated psychiatric conditions or a combination or interaction between both. Overall, the better controlled studies that show a direct correlation between childhood abuse and brain measures suggest that the most prominent deficits associated with early childhood abuse are in the function and structure of lateral and ventromedial fronto-limbic brain areas and networks that mediate behavioural and affect control. Future, large scale multimodal neuroimaging studies in medication-na&#239;ve subjects, however, are needed that control for psychiatric co-morbidities in order to elucidate the structural and functional brain sequelae that are associated with early environmental adversity, independently of secondary co-morbid conditions

Meta-analysis of fMRI studies of timing in attention-deficit hyperactivity disorder (ADHD)

AbstractAttention-deficit hyperactivity disorder (ADHD) is associated with deficits in timing functions with, however, inconclusive findings on the underlying neurofunctional deficits. We therefore conducted a meta-analysis of 11 functional magnetic resonance imaging (fMRI) studies of timing in ADHD, comprising 150 patients and 145 healthy controls. Peak coordinates were extracted from significant case–control activation differences as well as demographic, clinical, and methodological variables. In addition, meta-regression analyses were used to explore medication effects.The most consistent deficits in ADHD patients relative to controls were reduced activation in typical areas of timing such as left inferior prefrontal cortex (IFC)/insula, cerebellum, and left inferior parietal lobe. The findings of left fronto-parieto-cerebellar deficits during timing functions contrast with well documented right fronto-striatal dysfunctions for inhibitory and attention functions, suggesting cognitive domain-specific neurofunctional deficits in ADHD. The meta-regression analysis showed that right dorsolateral prefrontal cortex (DLPFC) activation was reduced in medication-naïve patients but normal in long-term stimulant medicated patients relative to controls, suggesting potential normalization effects on the function of this prefrontal region with long-term psychostimulant treatment