Structural and functional connectivity changes in response to short-term neurofeedback training with motor imagery.

Recent findings have been challenging current understanding of how fast the human brain change its structural and functional connections in response to training. One powerful way to deepen the inner workings of human brain plasticity is using neurofeedback (NFB) by fMRI, a technique that allows self-induced brain plasticity by means of modulating brain activity in real time. In the present randomized, double-blind and sham-controlled study, we use NFB to train healthy individuals to reinforce brain patterns related to motor execution while performing a motor imagery task, with no overt movement. After 1 h of NFB training, participants displayed increased fractional anisotropy (FA) in the sensorimotor segment of corpus callosum and increased functional connectivity of the sensorimotor resting state network. Increased functional connectivity was also observed in the default mode network. These results were not observed in the control group, which was trained with sham feedback. To our knowledge, this is the first demonstration of white matter FA changes following a very short training schedule (<1 h). Our results suggest that NFB by fMRI can be an interesting tool to explore dynamic aspects of brain plasticity and open new venues for investigating brain plasticity in healthy individuals and in neurological conditions.

Zika virus impairs the development of blood vessels in a mouse model of congenital infection.

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.

In vivo detection of cortical plaques by MR imaging in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: In vivo detection of cortical lesions in patients with multiple sclerosis (MS) by MR imaging is hampered by several factors. Among them is the low contrast between small cortical lesions and surrounding cortical gray matter offered by present techniques. METHODS: T1-weighted 3D spoiled gradient-recalled-echo (SPGR) volumes and 2D fluid-attenuated inversion recovery (FLAIR) sequences of 22 patients with MS who had 12 monthly brain MR imaging examinations at 1.5T, using a quadrature head coil, were retrospectively analyzed. These serial studies were coregistered and averaged to generate a single high signal-to-noise ratio (SNR) mean image, which was used to identify cortical lesions. The means of 12 FLAIRs and SPGRs from 14 age- and sex-matched healthy volunteers were analyzed as well. RESULTS: No cortical lesions were found on images of healthy subjects. Eighty-six cortical lesions were identified in 13 (59.1%) patients, predominantly in the frontal lobe (73.3%); 23.3% of cortical lesions lay entirely in the cortex, whereas the remaining lesions invaded the white matter underneath. CONCLUSION: Averaging multiple SPGRs created a single high SNR volume, allowing identification of cortical lesions. Because data were obtained monthly for 1 year, the average image does not account for transient lesion activity. However, for cortical lesions that remained stable during this time, the findings are valid in demonstrating the importance of high SNR images for detecting cortical brain abnormalities in MS.

Tissue-specific imaging is a robust methodology to differentiate in vivo T1 black holes with advanced multiple sclerosis-induced damage.

BACKGROUND AND PURPOSE: Brains of patients with multiple sclerosis (MS) characteristically have "black holes" (BHs), hypointense lesions on T1-weighted (T1W) spin-echo (SE) images. Although conventional MR imaging can disclose chronic BHs (CBHs), it cannot stage the degree of their pathologic condition. Tissue-specific imaging (TSI), a recently introduced MR imaging technique, allows selective visualization of white matter (WM), gray matter (GM), and CSF on the basis of T1 values of classes of tissue. We investigated the ability of TSI-CSF to separate CBHs with longer T1 values, which likely represent lesions containing higher levels of destruction and unbound water. MATERIALS AND METHODS: Eighteen patients with MS, who had already undergone MR imaging twice (24 months apart) on a 1.5T scanner, underwent a 3T MR imaging examination. Images acquired at 1.5T included sequences of precontrast and postcontrast T1W SE, T2-weighted (T2W) SE, and magnetization transfer (MT). Sequences obtained at 3T included precontrast and postcontrast T1W SE, T2W SE, T1 inversion recovery prepared fast spoiled gradient recalled-echo (IR-FSPGR) and TSI. A BH on the 3T-IR-FSPGR was defined as a CBH if seen as a hypointense, nonenhancing lesion with a corresponding T2 abnormality for at least 24 months. CBHs were separated into 2 groups: those visible as hyperintensities on TSI-CSF (group A), and those not appearing on the TSI-CSF (group B). RESULTS: Mean MT ratios of group-A lesions (0.22 +/- 0.06, 0.13-0.35) were lower (F(1,13) = 60.39; P < .0001) than those of group-B lesions (0.32 +/- 0.03, 0.27-0.36). CONCLUSIONS: Group-A lesions had more advanced tissue damage; thus, TSI is a potentially valuable method for qualitative and objective identification.

Thalamic involvement and its impact on clinical disability in patients with multiple sclerosis: a diffusion tensor imaging study at 3T.

BACKGROUND AND PURPOSE: Several studies suggest that grey matter involvement may play a role in multiple sclerosis (MS) pathology. Diffusion tensor imaging (DTI) at 3T was used to investigate the presence of damage to the normal-appearing thalamus in MS and its relationship with disability. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting (RR, n = 13, age = 41.7 +/- 6.1, Expanded Disability Status Scale [EDSS] score = 2.2 +/- 1.2) and secondary-progressive (n = 11, age = 46.9 +/- 9.6, EDSS = 5.9 +/- 1.0) MS and 24 age- and sex-matched healthy volunteers were studied. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in regions of interest of normal-appearing thalamus. We examined group differences in MD and FA and correlations between DTI-derived metrics and clinical or imaging measures of disease. RESULTS: Patients with MS had higher thalamic FA (P < .0001) and MD (P = .035) than volunteers. MD values correlated with the Paced Auditory Serial Addition Task (r = -0.43, P = .034) and motor EDSS (r = 0.47, P = .021) scores. In patients with RRMS, MD values correlated with global EDSS (r = 0.75, P = .003) and motor EDSS (r = 0.68, P = .010). Correlations were found between MD values and T1 and T2 lesion load (r = 0.58, P < .05) and brain parenchymal fraction (r = -0.46, P < .05). CONCLUSIONS: DTI was able to detect abnormalities in normal-appearing thalamus of patients with MS. The strength of association between thalamic DTI measures and functional impairment was in the same range as those seen with standard MR imaging disease measures. The assessment of the integrity of the thalamus with DTI is a promising metric as a marker of disease for future studies.