Phylogenetic threats such as spiders evoke our deepest primitive fears. When close or looming, such threats engage evolutionarily conserved monitoring systems and defense reactions that promote ...self-preservation. With the use of a modified behavioral approach task within functional MRI, we show that, as a tarantula was placed closer to a subject's foot, increased experiences of fear coincided with augmented activity in a cascade of fear-related brain networks including the periaqueductal gray, amygdala, and bed nucleus of the stria terminalis. Activity in the amygdala was also associated with underprediction of the tarantula's threat value and, in addition to the bed nucleus of the stria terminalis, with monitoring the tarantula's threat value as indexed by its direction of movement. Conversely, the orbitofrontal cortex was engaged as the tarantula grew more distant, suggesting that this region emits safety signals or expels fear. Our findings fractionate the neurobiological mechanisms associated with basic fear and potentially illuminate the perturbed reactions that characterize clinical phobias.
In this paper, we present results from the weak-lensing shape measurement GRavitational lEnsing Accuracy Testing 2010 (GREAT10) Galaxy Challenge. This marks an order of magnitude step change in the ...level of scrutiny employed in weak-lensing shape measurement analysis. We provide descriptions of each method tested and include 10 evaluation metrics over 24 simulation branches.
GREAT10 was the first shape measurement challenge to include variable fields; both the shear field and the point spread function (PSF) vary across the images in a realistic manner. The variable fields enable a variety of metrics that are inaccessible to constant shear simulations, including a direct measure of the impact of shape measurement inaccuracies, and the impact of PSF size and ellipticity, on the shear power spectrum. To assess the impact of shape measurement bias for cosmic shear, we present a general pseudo-C
ℓ formalism that propagates spatially varying systematics in cosmic shear through to power spectrum estimates. We also show how one-point estimators of bias can be extracted from variable shear simulations.
The GREAT10 Galaxy Challenge received 95 submissions and saw a factor of 3 improvement in the accuracy achieved by other shape measurement methods. The best methods achieve sub-per cent average biases. We find a strong dependence on accuracy as a function of signal-to-noise ratio, and indications of a weak dependence on galaxy type and size. Some requirements for the most ambitious cosmic shear experiments are met above a signal-to-noise ratio of 20. These results have the caveat that the simulated PSF was a ground-based PSF. Our results are a snapshot of the accuracy of current shape measurement methods and are a benchmark upon which improvement can be brought. This provides a foundation for a better understanding of the strengths and limitations of shape measurement methods.
See Meder and Siebner (doi:10.1093/brain/awy195) for a scientific commentary on this article.
Impulsivity and disinhibition are major symptoms of frontotemporal dementia, with limited treatment ...options. Using magnetoencephalography, Hughes et al. characterise the neural oscillatory dynamics of response inhibition, revealing impaired beta-band desynchronization and disrupted cross-frequency coupling in patients. This cortical oscillatory signature of disease represents a potential pharmacological target for symptomatic treatment.
Abstract
The distribution of pathology in frontotemporal dementia is anatomically selective, to distinct cortical regions and with differential neurodegeneration across the cortical layers. The cytoarchitecture and connectivity of cortical laminae preferentially supports frequency-specific oscillations and hierarchical information transfer between brain regions. We therefore predicted that in frontotemporal dementia, core functional deficits such as disinhibition would be associated with differences in the frequency spectrum and altered cross-frequency coupling between frontal cortical regions. We examined this hypothesis using a 'Go-NoGo' response inhibition paradigm with 18 patients with behavioural variant frontotemporal dementia and 20 healthy aged-matched controls during magnetoencephalography. During Go and NoGo trials, beta desynchronization was severely attenuated in patients. Beta power was associated with increased impulsivity, as measured by the Cambridge Behavioural Inventory, a carer-based questionnaire of changes in everyday behaviour. To quantify the changes in cross-frequency coupling in the frontal lobe, we used dynamic causal modelling to test a family of hierarchical casual models, which included the inferior frontal gyrus, pre-supplementary motor area (preSMA) and primary motor cortex. This analysis revealed evidence for cross-frequency coupling in a fully connected network in both groups. However, in the patient group, we identified a significant loss of reciprocal connectivity of the inferior frontal gyrus, particularly for interactions in the gamma band and for theta to alpha coupling. Importantly, although prefrontal coupling was diminished, gamma connectivity between preSMA and motor cortex was enhanced in patients. We propose that the disruption of behavioural control arises from reduced frequency-specific connectivity of the prefrontal cortex, together with a hyper-synchronous reorganization of connectivity among preSMA and motor regions. These results are supported by preclinical evidence of the selectivity of frontotemporal lobar degeneration on oscillatory dynamics, and provide a clinically relevant yet precise neurophysiological signature of behavioural control as a potential pharmacological target for early phase experimental medicines studies.
Simultaneous multislice (SMS) imaging can be used to decrease the time between acquisition of fMRI volumes, which can increase sensitivity by facilitating the removal of higher-frequency artifacts ...and boosting effective sample size. The technique requires an additional processing step in which the slices are separated, or unaliased, to recover the whole brain volume. However, this may result in signal “leakage” between aliased locations, i.e., slice “leakage,” and lead to spurious activation (decreased specificity). SMS can also lead to noise amplification, which can reduce the benefits of decreased repetition time. In this study, we evaluate the original slice-GRAPPA (no leak block) reconstruction algorithm and acceleration factor (AF = 8) used in the fMRI data in the young adult Human Connectome Project (HCP). We also evaluate split slice-GRAPPA (leak block), which can reduce slice leakage. We use simulations to disentangle higher test statistics into true positives (sensitivity) and false positives (decreased specificity). Slice leakage was greatly decreased by split slice-GRAPPA. Noise amplification was decreased by using moderate acceleration factors (AF = 4). We examined slice leakage in unprocessed fMRI motor task data from the HCP. When data were smoothed, we found evidence of slice leakage in some, but not all, subjects. We also found evidence of SMS noise amplification in unprocessed task and processed resting-state HCP data.
•In simulations, SMS improves sensitivity in motor cortex.•Split slice-GRAPPA reduces slice leakage to improve specificity.•Moderate acceleration factors (AF = 4) reduce spatially structured measurement error.•Slice leakage in smoothed unprocessed HCP data (AF = 8) in some, not all, subjects.•Evidence of noise amplification in unprocessed and processed HCP data.
Malignancy-associated pruritus Rowe, B.; Yosipovitch, G.
European journal of pain,
January 2016, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Malignancy‐associated pruritus can be the result of a neoplasm's local effect on tissue or due to the systemic reaction to malignancy. A systemic reaction to malignancy has been termed ...‘paraneoplastic itch’ and can be the first sign of an underlying malignancy. Paraneoplastic itch is most commonly caused by lymphoproliferative malignancies, and severity of itch correlates with stage of disease in Hodgkin's lymphoma and polycythemia vera. Non‐melanoma skin cancer is the most common type of malignancy‐associated pruritus, and recent data indicate that pruritus is associated with more than one‐third of non‐melanoma skin cancers. Cutaneous T‐cell lymphomas (CTCL), particularly more advanced stages, cause intractable pruritus and recent investigations into the pathophysiology of CTCL‐associated itch have implicated cyotokine interleukin‐31 as a putative mediator. Treatments that reduce itch in CTCL patients, such as histone deacetylase inhibitors (HDACi), Mogamulizumab, a novel monoclonal antibody against chemokine receptor type‐4, and oral corticosteroids, have demonstrated a correlation between their anti‐pruritic effect and reduced serum levels of interleukin‐31.
Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in ...decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I-III) and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method) to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1) tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2) tests of motor inhibitory control, and the self-report behavioural approach system, (3) time estimation and delay aversion, and (4) reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2) and (3). The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and that it is not a unitary phenomenon. A better understanding of the structure of impulsivity in Parkinson's disease will support more evidence-based and effective strategies to treat impulsivity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
‘Intentional binding’ describes the perceived temporal attraction between a voluntary action and its sensory consequence. Binding has been used in health and disease as an indirect measure of ...awareness of action or agency, that is, the sense that one controls one’s own actions. It has been proposed that binding results from cue integration, in which a voluntary action provides information about the timing of its consequences or vice versa. The perception of the timing of either event is then a weighted average, determined according to the reliability of each of these two cues. Here we tested the contribution of cue integration to the perception of action and its sensory effect in binding, that is, action and tone binding, by manipulating the sensory reliability of the outcome tone. As predicted, when tone reliability was reduced, action binding was diminished and tone binding was increased. However, further analyses showed that cue integration accounted for changes in action binding, but not tone binding. These findings establish a role for cue integration in action binding and support the growing evidence suggesting that action and tone binding are, at least in part, driven by distinct mechanisms.
Voluntary action control requires selection of appropriate responses and stopping of inappropriate responses. Selection and stopping are often investigated separately, but they appear to recruit ...similar brain regions, including the pre-supplementary motor area (preSMA) and inferior frontal gyrus. We therefore examined the evidence for overlap of selection and stopping using two approaches: a meta-analysis of existing studies of selection and stopping, and a novel within-subject fMRI study in which action selection and a stop signal task were combined factorially. The novel fMRI study also permitted us to investigate hypotheses regarding a common mechanism for selection and stopping. The preSMA was identified by both methods as common to selection and stopping. However, stopping a selected action did not recruit preSMA more than stopping a specified action, nor did stop signal reaction times differ significantly across the two conditions. These findings suggest that the preSMA supports both action selection and stopping, but the two processes may not require access to a common inhibition mechanism. Instead, the preSMA might represent information about potential actions that is used in both action selection and stopping in order to resolve conflict between competing available responses.
•GingerALE meta-analysis shows overlap of action selection and stopping in preSMA.•Within-subjects fMRI study confirms overlap using same stimuli and subjects.•Although selection and stopping overlap, there is no behavioural interaction.•The preSMA may support the representation of competing action options.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using 11CPK11195 positron emission
tomography (PET). Five older participants with major ...depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
11CPK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
PDF
