Several neuroimaging studies have consistently shown activations of areas surrounding the temporo-parietal junction (TPJ) during tasks exploring the sense of agency. Beyond TPJ, activations in different structures, such as the dorsolateral prefrontal cortex (dLPFC), the pre-supplementary motor area (pre-SMA), the insula and the precuneus have been reported. Moreover, a possible dissociation between self- and external-agency attribution has been suggested. To test the hypothesis of distinct neural correlates for self- and external-agency attribution a quantitative meta-analysis, based on activation likelihood estimation (ALE) method, across 15 PET and fMRI studies (228 subjects) was conducted. Results show converging activations including the TPJ, pre-SMA, precuneus and dorsomedial prefrontal cortex (dMPFC) in external-agency, while insula activation was related to self-agency. We discuss these findings, highlighting the role of the insula, and calling for the use of alternative paradigms such as intentional binding and interactive imitation to study agency.

The insula is the fifth lobe of the brain and it is the least known. Hidden under the temporal, frontal and parietal opercula, as well as under dense arterial and venous vessels, its accessibility is particularly restricted. Functional data on this region in humans, therefore, are scarce and the existing evidence makes conclusions on its functional and somatotopic organization difficult. 5 patients with intractable epilepsy underwent an invasive presurgical evaluation with implantation of diagnostic invasive-depth electrodes, including insular electrodes that were inserted using a mesiocaudodorsal to laterorostroventral approach. Altogether 113 contacts were found to be in the insula and were stimulated with alternating currents during preoperative monitoring. Different viscerosensitive and somatosensory phenomena were elicited by stimulation of these electrodes. A relatively high density of electrode contacts enabled us to delineate several functionally distinct areas within the insula. We found somatosensory symptoms to be restricted to the posterior insula and a subgroup of warmth or painful sensations in the dorsal posterior insula. Viscerosensory symptoms were elicited by more anterior electrode contacts with a subgroup of gustatory symptoms occurring after stimulation of electrode contacts in the central part of the insula. The anterior insula did not show reproducible responses to stimulation. In line with previous studies, we found evidence for somato- and viscerosensory cortex in the insula. In addition, our results suggest that there is a predominantly posterior and central distribution of these functions in the insular lobe.

In this study, we used tract-based spatial statistics (TBSS) to analyze diffusion tensor MR imaging (DTI) data acquired from the rat brain, ex vivo, for the first time. The aim was to highlight potential changes in the whole brain anatomy in the kainic acid model of epilepsy, and further characterize the changes with histology. Increased FA was observed in dorsal endopiriform nucleus, external capsule, corpus callosum, dentate gyrus, thalamus, and optic tract. A decrease in FA was seen in the horizontal limb of the diagonal band, stria medullaris, habenula, entorhinal cortex, and superior colliculus. Some of the areas have been described in kainic acid model before. However, we also found regions that to our knowledge have not been previously reported to undergo structural changes, in this model, including stria medullaris, nucleus of diagonal band, habenula, superior colliculus, external capsule, corpus callosum, and optic tract. Four of the areas highlighted in TBSS (dentate gyrus, entorhinal cortex, thalamus and stria medullaris) were analyzed in more detail with Nissl, Timm, and myelin-stained histological sections, and with polarized light microscopy. TBSS together with targeted histology confirmed that DTI changes were associated with altered myelination, neurodegeneration, and/or calcification of the tissue. Our data demonstrate that DTI in combination with TBSS has a great potential to facilitate the discovery of previously undetected anatomical changes in animal models of brain diseases.

Hypobaric hypoxia, encountered at high altitude, could result in severe consequences. Ascorbic acid (AA) and α-tocopherol (αTC), the two readily available over-the-counter antioxidants, are known to protect nervous tissue against oxidative stress. Here we study whether AA or αTC supplement starting prenatally protects animals against hypobaric hypoxic challenge at adulthood. Expressions of c-fos and the NR1 subunit of the N-methyl-d-aspartate receptors in the nucleus tractus solitarius (NTS) subserving cardiorespiratory functions were investigated. AA and αTC supplement reduced the number of c-fos immunoreactive neurons and intensity of NR1 expression in young and adult animals under normoxia. The treatment, in addition, attenuated the activation of NTS neurons, in terms of c-fos and NR1 expressions, and reduced the anxiety behaviors of adult rats subjected to hypobaric hypoxic challenge. Reduction of c-fos immunoreactive neurons was found concentrated in the chemoreceptor, baroreceptor, and tracheobronchial tree NTS subnuclei that receive corresponding afferents. The protective effect was not found in normal adult animals supplemented with AA or αTC a week before hypobaric hypoxic challenge. In short, prenatal and sustained AA or αTC supplement altered NTS substrate and ameliorated animals' reactions to hypobaric hypoxic insult, suggesting that this may be considered to protect animals from hypoxic insults from young to adult.

Induction of the activity-regulated cytoskeleton-associated protein gene (Arc), one of the immediate early genes, in the brain correlates with various sensory processes, natural behaviors, and pathological conditions. Arc is also involved in synaptic plasticity during development. Thus, in vivo monitoring of Arc expression is useful for the analysis of physiological and pathological conditions in the brain. Recently, in vivo imaging of Arc expression using various green fluorescent protein-based probes has been reported; however, these probes can only be applied for the detection of fluorescence signals from superficial layers of the cortex with some autofluorescence noise. Here, we generated a novel transgenic mouse strain to monitor the neuronal-activity-dependent Arc expression using bioluminescence signals in vivo. Because of the very high sensitivity with a high signal-to-noise ratio, we detected neuronal-activity-dependent plastic changes in the bioluminescence signal intensity in the mouse visual cortex after visual deprivation, suggesting structural plasticity after peripheral lesions in adults. We also detected drastic changes in bioluminescence signals after seizure induction with kainic acid. Our novel mouse strain will be valuable for the continuous monitoring of neuronal-activity-dependent Arc expression in the brain under physiological and pathological conditions.