Serial assessment of iron in the motor cortex in limb-onset amyotrophic lateral sclerosis using quantitative susceptibility mapping.

BACKGROUND: Dysregulation of iron in the cerebral motor areas has been hypothesized to occur in individuals with amyotrophic lateral sclerosis (ALS). There is still limited knowledge regarding iron dysregulation in the progression of ALS pathology. Our objectives were to use magnetic resonance based quantitative susceptibility mapping (QSM) to investigate the association between iron dysregulation in the motor cortex and clinical manifestations in patients with limb-onset ALS, and to examine changes in the iron concentration in the motor cortex in these patients over a 6-month period. METHODS: Iron concentration was investigated using magnetic resonance based QSM in the primary motor cortex and the pre-motor area in 13 limb-onset ALS patients (including five lumbar onset, six cervical onset and two flail arm patients), and 11 age- and sex-matched control subjects. Nine ALS patients underwent follow-up scans at 6 months. RESULTS: Significantly increased QSM values were observed in the left posterior primary motor area (P=0.02, Cohen's d =0.9) and right anterior primary motor area (P=0.02, Cohen's d =0.92) in the group of limb-onset ALS patients compared to that of control subjects. Increased QSM was observed in the primary motor and pre-motor area at baseline in patients with lumbar onset ALS patients, but not cervical limb-onset ALS patients, compared to control subjects. No significant change in QSM was observed at the 6-month follow-up scans in the ALS patients. CONCLUSIONS: The findings suggest that iron dysregulation can be detected in the motor cortex in limb-onset ALS, which does not appreciably change over a further 6 months. Individuals with lumbar onset ALS appear to be more susceptible to motor cortex iron dysregulation compared to the individuals with cervical onset ALS. Importantly, this study highlights the potential use of QSM as a quantitative radiological indicator in early disease diagnosis in limb-onset ALS and its subtypes. Our serial scans results suggest a longer period than 6 months is needed to detect significant quantitative changes in the motor cortex.

Partial volume model for brain MRI scan using MP2RAGE.

MP2RAGE is a T1 weighted MRI sequence that estimates a composite image providing much reduction of the receiver bias, has a high intensity dynamic range, and provides an estimate of T1 mapping. It is, therefore, an appealing option for brain morphometry studies. However, previous studies have reported a difference in cortical thickness computed from MP2RAGE compared with widely used Multi-Echo MPRAGE. In this article, we demonstrated that using standard segmentation and partial volume estimation techniques on MP2RAGE introduces systematic errors, and we proposed a new model to estimate partial volume of the cortical gray matter. We also included in their model a local estimate of tissue intensity to take into account the natural variation of tissue intensity across the brain. A theoretical framework is provided and validated using synthetic and physical phantoms. A repeatability experiment comparing MPRAGE and MP2RAGE confirmed that MP2RAGE using our model could be considered for structural imaging in brain morphology study, with similar cortical thickness estimate than that computed with MPRAGE. Hum Brain Mapp 38:5115-5127, 2017. © 2017 Wiley Periodicals, Inc.

Led into temptation? Rewarding brand logos bias the neural encoding of incidental economic decisions.

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance.

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE(-/-)) and compared with wild-type littermates. Compared with wild-type littermates, ACE(-/-) mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE(-/-) mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE(-/-) mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE(-/-) mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Neuroscience data and tool sharing: a legal and policy framework for neuroinformatics.

The requirements for neuroinformatics to make a significant impact on neuroscience are not simply technical--the hardware, software, and protocols for collaborative research--they also include the legal and policy frameworks within which projects operate. This is not least because the creation of large collaborative scientific databases amplifies the complicated interactions between proprietary, for-profit R&D and public "open science." In this paper, we draw on experiences from the field of genomics to examine some of the likely consequences of these interactions in neuroscience. Facilitating the widespread sharing of data and tools for neuroscientific research will accelerate the development of neuroinformatics. We propose approaches to overcome the cultural and legal barriers that have slowed these developments to date. We also draw on legal strategies employed by the Free Software community, in suggesting frameworks neuroinformatics might adopt to reinforce the role of public-science databases, and propose a mechanism for identifying and allowing "open science" uses for data whilst still permitting flexible licensing for secondary commercial research.