We used optogenetic mice to investigate possible nonlinear responses of the medial prefrontal cortex (mPFC) local network to light stimuli delivered by a 473 nm laser through a fiber optics. Every 2 s, a brief 10 ms light pulse was applied and the local field potentials (LFPs) were recorded with a 10 kHz sampling rate. The experiment was repeated 100 times and we only retained and analyzed data from six animals that showed stable and repeatable response to optical stimulations. The presence of nonlinearity in our data was checked using the null hypothesis that the data were linearly correlated in the temporal domain, but were random otherwise. For each trail, 100 surrogate data sets were generated and both time reversal asymmetry and false nearest neighbor (FNN) were used as discriminating statistics for the null hypothesis. We found that nonlinearity is present in all LFP data. The first 0.5 s of each 2 s LFP recording were dominated by the transient response of the networks. For each trial, we used the last 1.5 s of steady activity to measure the phase resetting induced by the brief 10 ms light stimulus. After correcting the LFPs for the effect of phase resetting, additional preprocessing was carried out using dendrograms to identify “similar” groups among LFP trials. We found that the steady dynamics of mPFC in response to light stimuli could be reconstructed in a three-dimensional phase space with topologically similar “8”-shaped attractors across different animals. Our results also open the possibility of designing a low-dimensional model for optical stimulation of the mPFC local network.

No abstract

No abstract

Tom Fagan: I am Tom Fagan from the Alzheimer Research Forum and I will be moderating today. John Trojanowski, would you like to start the ball rolling? John Trojanowski: Okay, Tom. Briefly, we will focus here on chemical analyte biomarkers in various bodily fluids such as cerebrospinal fluid (CSF), urine, blood, etc., and while genetics may come up, too, we will save imaging biomarkers for another time. Concerning apolipoprotein E (ApoE): It does seem to be critical to consider this for cohort assignment as demonstrated in the recent NEJM paper from R. Peterson [1] on mild cognitive impairment (MCI), and we will do this as well in the Alzheimer Disease Neuroimaging Initiative (ADNI) study. Anne Fagan: John, what is your gut feeling about the potential utility of urine showing decent biomarkers? John Trojanowski: So far, urine has seemed fruitful for studies of isoprostanes, although it depends on which one is measured and the method, but I am not certain if other analytes in urine are informative [2-4]. 1 Note: The transcript has been edited for clarity and accuracy. Anne Fagan: We are already seeing some differences in levels of Aβ42 in ApoE4-positive versus ApoE4negative folks in our antecedent study, but not other CSF markers, although the data are very preliminary. It suggests that perhaps Aβ42 is the first thing to change. We must verify with follow-up, of course. Tom Fagan: Anne, do you have indications that urine analysis might prove useful? Anne Fagan: Tom, we are not collecting urine. It may be too far down the line (i.e., processed) to be meaningful, but the idea is very clinically appealing. John Trojanowski: Les, do you have information on other urine analytes? Les Shaw: John, for AD, no. John Trojanowski: Anne, what do the receiver operating curves (ROCs) look like in the studies you mention, and perhaps the group would benefit from a definition of "antecedent," as this is not on everyone's radar screen? [ROCs can provide useful information on the sensitivity and specificity of clinical measurements.] Anne Fagan: True, John. We have not done formal ROC analysis yet. I use "antecedent" to mean biomark

No abstract

No abstract