Abnormal thalamocortical structural and functional connectivity in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is the most common idiopathic generalized epilepsy, characterized by frequent myoclonic jerks, generalized tonic-clonic seizures and, less commonly, absences. Neuropsychological and, less consistently, anatomical studies have indicated frontal lobe dysfunction in the disease. Given its presumed thalamo-cortical basis, we investigated thalamo-cortical structural connectivity, as measured by diffusion tensor imaging, in a cohort of 28 participants with juvenile myoclonic epilepsy and detected changes in an anterior thalamo-cortical bundle compared with healthy control subjects. We then investigated task-modulated functional connectivity from the anterior thalamic region identified using functional magnetic resonance imaging in a task consistently shown to be impaired in this group, phonemic verbal fluency. We demonstrate an alteration in task-modulated connectivity in a region of frontal cortex directly connected to the thalamus via the same anatomical bundle, and overlapping with the supplementary motor area. Further, we show that the degree of abnormal connectivity is related to disease severity in those with active seizures. By integrating methods examining structural and effective interregional connectivity, these results provide convincing evidence for abnormalities in a specific thalamo-cortical circuit, with reduced structural and task-induced functional connectivity, which may underlie the functional abnormalities in this idiopathic epilepsy.

Clustering probabilistic tractograms using independent component analysis applied to the thalamus.

The connectivity information contained in diffusion tensor imaging (DTI) has previously been used to parcellate cortical and subcortical regions based on their connectivity profiles. The aim of the current study is to investigate the utility of a novel approach to connectivity based parcellation of the thalamus using probabilistic tractography and independent component analysis (ICA). We use ICA to identify spatially coherent tractograms as well as their underlying seed regions, in a single step. We compare this to seed-based tractography results and to an established and reliable approach to parcellating the thalamus based on the dominant cortical connection from each thalamic voxel (Behrens et al., 2003a,b). The ICA approach identifies thalamo-cortical pathways that correspond to known anatomical connections, as well as parcellating the underlying thalamus in a spatially similar way to the connectivity based parcellation. We believe that the use of such a multivariate method to interpret the complex datasets created by probabilistic tractography may be better suited than other approaches to parcellating brain regions.

Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice.

Astaxanthin is an antioxidant with immunomodulatory, anti-inflammatory and anticancer properties. This study evaluated the use of dietary astaxanthin to decrease oxidative stress and improve cardiac function, thereby providing a potential cardioprotective supplement. Female BALB/c mice (8 weeks of age) were fed a semi-synthetic diet containing 0, 0.02 or 0.08% astaxanthin for 8 weeks. Cardiac function was assessed by echocardiography bi-weekly, and blood and tissue samples were collected at 8 weeks. Plasma astaxanthin concentrations increased (p<0.05) dose-dependently to 0.5 and 4 mumol/l in the astaxanthin-supplemented mice. Blood glutathione concentrations and lymphocyte mitochondrial membrane potential were not significantly affected by astaxanthin treatment. However, mice fed 0.08% astaxanthin had higher (p<0.05) heart mitochondrial membrane potential and contractility index compared to the control group. These results support the possible use of dietary astaxanthin for cardiac protection.

Effect of dietary astaxanthin at different stages of mammary tumor initiation in BALB/c mice.

The effects of astaxanthin on tumor growth, cardiac function and immune response in mice were studied. Female BALB/c mice were fed a control diet (diet C) for 8 weeks, 0.005% astaxathin for 8 weeks (diet A), or diet C for weeks 1-5 followed by diet A thereafter (diet CA). Mice were injected with a mammary tumor cell line on day 7 and tumor growth was measured daily. Mice fed diet A had extended tumor latency and lower tumor volume (p<0.05). Interestingly, those fed diet CA showed the fastest tumor growth. Astaxanthin feeding elevated plasma astaxanthin concentrations; there was no difference in plasma astaxanthin between mice fed CA and those fed A. Mice fed diet A, but not CA, had a higher (p<0.05) natural killer cell subpopulation and plasma interferon-gamma concentration compared to those fed diet C. Astaxanthin delayed tumor growth and modulated immune response, but only when astaxanthin was given before tumor initiation. This suggests that an adequate blood astaxanthin status is needed to protect against tumor initiation; conversely, astaxanthin supplementation after tumor initiation may be contraindicated.