A: Seizure occurrence after perfusion of the <i>in</i><i>vitro</i> isolated guinea pig brain with different K⁺ salt solutions.

<p>The white columns represent the total number of experiments. The light grey, dark grey and black columns mark the effects of the perfusion of K⁺ salts at 8, 14.2m 20 mM, respectively. <b>B</b>: Time at onset (black columns) and duration (white columns) of seizure activity after perfusion with 14.2 KPF₆, 14.2 mM KClO₄ and 20 mM KBF₄. <b>C</b>: Brain parenchyma concentration of two salts (KPF₆ and KBF₄) estimated by ¹⁹F MR spectroscopy on CA1-EC specimens, collected after arterial perfusion with 14.2 mM KPF₆ (n= 4; black column) and 20 mM KBF₄ (n= 3; grey column). </p

KPF₆ 14.2 mM perfusion induced large amplitude depolarization events that propagated through the cortical mantel, from the hippocampus to the entorhinal (EC) and piriform cortex (PC).

<p>These events were interpreted as spreading depolarization phenomena (Somjen 2001). </p

Effects of 4.2 mM KPF₆ (A), 14.2 mM KClO₄ (B) and 20 mM KCl (C) on the field potentials evoked in the piriform cortex by lateral olfactory tract (LOT) stimulation.

<p>Left, middle and right traces: before, during and after washout of the K⁺ salts, respectively.</p

A. Schematic protocol of the experiments. Electrophysiological recordings are performed for the entire experimental period

<p>Each perfusion of salts lasted 15 min. and was followed by 30 min. wash-out. Brain tissue samples were than collected and processed for the ¹⁹F MR spectroscopy. <b>B:</b> Structures of KX salts (X= PF₆^-, BF₄^-, ClO₄^-, Br^-, AcO^- and Cl^-) and electrostatic potential surfaces (B3LYP/6-311+G**) of individuals ions and ion pairs. Blue regions indicate positive potentials and red regions negative ones. Maximum values of the electrostatic potential, at K atom, and minimum values, at O, F, Br and Cl atoms are indicated besides each structure. Molecular volumes are also reported (ų).</p

Effects of perfusion of K⁺ salts in the <i>in</i><i>vitro</i> isolated guinea pig brain.

<p>A scheme of the position of the recording and stimulating (S1, on the lateral olfactory tract) electrodes is shown in the upper part of the figure. The upper set of traces illustrates the effect of 14.2 mM KPF₆ perfusion (right) compared to control (left); seizure activity was induced by this salt. In the lower part of the figure the effect of perfusion with 14.2 mM KClO₄ is shown. PC: piriform cortex; EC: entorhinal cortex; HIP: CA1 region of the hippocampus.</p

Interferon-a acutely impairs whole-brain functional connectivity network architecture - a preliminary study

Interferon-alpha (IFN-a) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-a rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-a) on whole brain functional connectivity architecture and its relationship to IFN-a-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-a-based therapy were scanned at baseline and 4h after their first IFN-a dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-a was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-a. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-a rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-a

Demographic information of the sample.

<p>Demographic information and neuropsychological tests' scores. Chi square was used for gender comparison. One-way ANOVA test with Bonferroni correction for multiple comparisons was used for age, education-year, and MMSE score comparisons (significance level: : p_corr<0.05).</p>a<p>: Significant compared to aMCI and control groups;</p>b<p>: Significant compared to AD group.</p