SciCombinator

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Concept: Neuroimaging

209

Creativity is a vast construct, seemingly intractable to scientific inquiry-perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR). Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS). We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981). We provide a perspective, involving aspects of the default mode network (DMN), which might provide a “first approximation” regarding how creative cognition might map on to the human brain.

Concepts: Brain, Medical imaging, Neuroimaging, Nuclear magnetic resonance, Magnetic resonance imaging, Thought, Diffusion MRI, In vivo magnetic resonance spectroscopy

187

Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry.

Concepts: Psychology, Neuroimaging, Neuroscience, Addiction, Mental disorder, Functional magnetic resonance imaging, Functional neuroimaging, Internet addiction disorder

178

Several observations suggest that overlearned ordinal categories (e.g., letters, numbers, weekdays, months) are processed differently than non-ordinal categories in the brain. In synesthesia, for example, anomalous perceptual experiences are most often triggered by members of ordinal categories (Rich et al., 2005; Eagleman, 2009). In semantic dementia (SD), the processing of ordinal stimuli appears to be preserved relative to non-ordinal ones (Cappelletti et al., 2001). Moreover, ordinal stimuli often map onto unconscious spatial representations, as observed in the SNARC effect (Dehaene et al., 1993; Fias, 1996). At present, little is known about the neural representation of ordinal categories. Using functional neuroimaging, we show that words in ordinal categories are processed in a fronto-temporo-parietal network biased toward the right hemisphere. This differs from words in non-ordinal categories (such as names of furniture, animals, cars, and fruit), which show an expected bias toward the left hemisphere. Further, we find that increased predictability of stimulus order correlates with smaller regions of BOLD activation, a phenomenon we term prediction suppression. Our results provide new insights into the processing of ordinal stimuli, and suggest a new anatomical framework for understanding the patterns seen in synesthesia, unconscious spatial representation, and SD.

Concepts: Scientific method, Brain, Neuroimaging, Neuroscience, Human brain, Observation, Mind, Knowledge

172

A recent study demonstrates that intersubject variability in functional connectivity is heterogeneous across the cortex, with significantly higher variability in multimodal association cortex. Rather than being ‘noise’, intersubject variability is invaluable for understanding principles of brain evolution and ontogenetic development, and for interpreting statistical maps in task-based functional neuroimaging studies.

Concepts: Brain, Developmental biology, Neuroimaging, Cerebral cortex, Evolutionary developmental biology, Functional neuroimaging

171

BACKGROUND: Although diffusion tensor imaging has been a major research focus for Alzheimer’s disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer’s disease. METHODS: The biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics), and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N = 21) and mild (N = 22) Alzheimer’s disease patients were examined as well as a longitudinal cohort (N = 16) that had been rescanned at 12 months. FINDINGS AND SIGNIFICANCE: The results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as ‘state-specific’ markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear ‘stage-specific’ and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the former two metrics correlate with dementia severity, but the latter two did not, it would appear that increased axial diffusivity represents an upstream event that precedes neuronal loss.

Concepts: Alzheimer's disease, Neuron, Medical imaging, Neuroimaging, Dementia, Diffusion MRI, Corpus callosum, Imaging

170

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, caused by progressive loss of motor neurons. Changes are widespread in the subcortical white matter in ALS. Diffusion tensor imaging (DTI) detects pathological changes in white matter fibres in vivo, based on alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. METHODS: 24 patients with ALS and 24 age-matched controls received 1.5T DTI.FA and ADC were analyzed using statistical parametric mapping. In 15 of the 24 ALS patients, a second DTI was obtained after 6 months. RESULTS: Decreased FA in the corticospinal tract (CST) and frontal areas confirm existing results. With a direct comparison of baseline and follow-up dataset, the progression of upper motor neuron degeneration, reflected in FA decrease, could be captured along the CST and in frontal areas. The involvement of cerebellum in the pathology of ALS, as suspected from functional MRI studies, could be confirmed by a reduced FA (culmen, declive). These structural changes correlated well with disease duration, ALSFRS-R, and physical and executive functions. CONCLUSION: DTI detects changes that are regarded as prominent features of ALS and thus, shows promise in its function as a biomarker. Using the technique herein, we could demonstrate DTI changes at follow-up which correlated well with clinical progression.

Concepts: Spinal cord, Neuroimaging, Magnetic resonance imaging, Amyotrophic lateral sclerosis, Neurodegenerative disorders, Cerebellum, Motor neuron, Stephen Hawking

169

BACKGROUND: Diffusion tensor imaging (DTI) is increasingly used in various diseases as a clinical tool for assessing the integrity of the brain’s white matter. Reduced fractional anisotropy (FA) and an increased apparent diffusion coefficient (ADC) are nonspecific findings in most pathological processes affecting the brain’s parenchyma. At present, there is no gold standard for validating diffusion measures, which are dependent on the scanning protocols, methods of the softwares and observers. Therefore, the normal variation and repeatability effects on commonly-derived measures should be carefully examined. METHODS: Thirty healthy volunteers (mean age 37.8 years, SD 11.4) underwent DTI of the brain with 3T MRI. Region-of-interest (ROI) -based measurements were calculated at eleven anatomical locations in the pyramidal tracts, corpus callosum and frontobasal area. Two ROI-based methods, the circular method (CM) and the freehand method (FM), were compared. Both methods were also compared by performing measurements on a DTI phantom. The intra- and inter-observer variability (coefficient of variation, or CV%) and repeatability (intra-class correlation coefficient, or ICC) were assessed for FA and ADC values obtained using both ROI methods. RESULTS: The mean FA values for all of the regions were 0.663 with the CM and 0.621 with the FM. For both methods, the FA was highest in the splenium of the corpus callosum. The mean ADC value was 0.727 x10-3 mm2/s with the CM and 0.747 x10-3 mm2/s with the FM, and both methods found the ADC to be lowest in the corona radiata. The CV percentages of the derived measures were < 13% with the CM and < 10% with the FM. In most of the regions, the ICCs were excellent or moderate for both methods. With the CM, the highest ICC for FA was in the posterior limb of the internal capsule (0.90), and with the FM, it was in the corona radiata (0.86). For ADC, the highest ICC was found in the genu of the corpus callosum (0.93) with the CM and in the uncinate fasciculus (0.92) with FM. CONCLUSIONS: With both ROI-based methods variability was low and repeatability was moderate. The circular method gave higher repeatability, but variation was slightly lower using the freehand method. The circular method can be recommended for the posterior limb of the internal capsule and splenium of the corpus callosum, and the freehand method for the corona radiata.

Concepts: Brain, Neuroimaging, Magnetic resonance imaging, Cerebrum, Diffusion, Diffusion MRI, Corpus callosum, Atomic diffusion

166

6-Fluoro-((18)F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, (123)I-metaiodobenzylguanidine (MIBG) and (111)In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for (123)I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data, could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and (68)Ga-labelled peptides.

Concepts: Cancer, Oncology, Nuclear medicine, Medical imaging, Positron emission tomography, Neuroimaging, Carcinoid, Single photon emission computed tomography

146

We often experience troubled sleep in a novel environment [1]. This is called the first-night effect (FNE) in human sleep research and has been regarded as a typical sleep disturbance [2-4]. Here, we show that the FNE is a manifestation of one hemisphere being more vigilant than the other as a night watch to monitor unfamiliar surroundings during sleep [5, 6]. Using advanced neuroimaging techniques [7, 8] as well as polysomnography, we found that the temporary sleep disturbance in the first sleep experimental session involves regional interhemispheric asymmetry of sleep depth [9]. The interhemispheric asymmetry of sleep depth associated with the FNE was found in the default-mode network (DMN) involved with spontaneous internal thoughts during wakeful rest [10, 11]. The degree of asymmetry was significantly correlated with the sleep-onset latency, which reflects the degree of difficulty of falling asleep and is a critical measure for the FNE. Furthermore, the hemisphere with reduced sleep depth showed enhanced evoked brain response to deviant external stimuli. Deviant external stimuli detected by the less-sleeping hemisphere caused more arousals and faster behavioral responses than those detected by the other hemisphere. None of these asymmetries were evident during subsequent sleep sessions. These lines of evidence are in accord with the hypothesis that troubled sleep in an unfamiliar environment is an act for survival over an unfamiliar and potentially dangerous environment by keeping one hemisphere partially more vigilant than the other hemisphere as a night watch, which wakes the sleeper up when unfamiliar external signals are detected.

Concepts: Neuroimaging, Sleep, Sleep deprivation, Sleep disorder, Sleep apnea, Polysomnography, Sleep medicine, Medial longitudinal fissure

141

Despite calls to incorporate population science into neuroimaging research, most studies recruit small, non-representative samples. Here, we examine whether sample composition influences age-related variation in global measurements of gray matter volume, thickness, and surface area. We apply sample weights to structural brain imaging data from a community-based sample of children aged 3-18 (N = 1162) to create a “weighted sample” that approximates the distribution of socioeconomic status, race/ethnicity, and sex in the U.S. Census. We compare associations between age and brain structure in this weighted sample to estimates from the original sample with no sample weights applied (i.e., unweighted). Compared to the unweighted sample, we observe earlier maturation of cortical and sub-cortical structures, and patterns of brain maturation that better reflect known developmental trajectories in the weighted sample. Our empirical demonstration of bias introduced by non-representative sampling in this neuroimaging cohort suggests that sample composition may influence understanding of fundamental neural processes.The influence of sample composition on human neuroimaging results is unknown. Here, the authors weight a large, community-based sample to better reflect the US population and describe how applying these sample weights changes conclusions about age-related variation in brain structure.

Concepts: Scientific method, Brain, Sampling, Structure, Neuroimaging, Sociology, Science, Weight