Modelling large motion events in fMRI studies of patients with epilepsy

EEG-correlated fMRI can provide localisation information on the generators of epileptiform discharges in patients with focal epilepsy. To increase the technique's clinical potential, it is important to consider ways of optimising the yield of each experiment while minimizing the risk of false-positive activation. Head motion can lead to severe image degradation and result in false-positive activation and is usually worse in patients than in healthy subjects. We performed general linear model fMRI data analysis on simultaneous EEG–fMRI data acquired in 34 cases with focal epilepsy. Signal changes associated with large inter-scan motion events (head jerks) were modelled using modified design matrices that include ‘scan nulling’ regressors. We evaluated the efficacy of this approach by mapping the proportion of the brain for which F-tests across the additional regressors were significant. In 95% of cases, there was a significant effect of motion in 50% of the brain or greater; for the scan nulling effect, the proportion was 36%; this effect was predominantly in the neocortex. We conclude that careful consideration of the motion-related effects in fMRI studies of patients with epilepsy is essential and that the proposed approach can be effective

The Peptide MS/MS-Fragmentome: A Set of Predictable Fragment Ions with Highly Redundant Sequence Information

Upon low energy collision induced dissociation (CID), multiply protonated peptides generate a set of interdependent fragment ions detectable by MS/MS, the \u27[peptide]n+-fragmentome\u27. In particular dynamic fragmentation of [peptide]n+ ions in a collision cell generates information-rich MS/MS spectra. Currently, database-supported annotations of peptide MS/MS spectra are mainly based on a combination of peptide molecular weight and y type fragment ions, leaving a considerable number of good-quality peptide MS/MS spectra in proteomics studies unannotated. This situation may be improved by a more complete use of the structural information present in the [peptide]n+-fragmentome. The presentation provides an overview on the fragment ions of multiply protonated peptides and their connectivity, comprising a ions, b ions, y ions, and neutral loss reactions from the N-, and C-terminus, and internal b ions. In the low-mass region, the unique set of 19 y1 ions and of the 190 b2 ions carries a particular message, since these ions define the N-or C-terminal amino acid(s). Further, the b1 ions of the basic residues K, H, W, and R carry a specific N-terminal information, which is redundant to that contained in the corresponding b2 ions and in the N-terminal neutral loss peaks. Redundant information is also found in b and y ion series and in complementary b/y ion pairs. The latter are particularly abundant when generated by proline- or aspartate-induced backbone cleavages. From complementary b/y ion pairs the molecular weight of the precursor ion can be reconstructed to confirm or determine its molecular weight. This procedure is helpful in case a mixture of precursor ions is isolated or in case a precursor ion of very low abundance is isolated. Information about the precursor ion charge state is also delivered by precursor ion reconstruction using MS/MS data. In the analysis of covalently modified peptides, reporter ions are of particular importance. These ions can be used for mining of MS/MS data sets for the occurrence of selected modifications. Examples are presented for selected modifications, such as acetylation and phosphorylation. In phosphorylation analysis neutral loss reactions are highly important, and may also carry redundant information, when observed both from the molecular ion and from fragment ions. Search tools, which fully incorporate the current knowledge about the [peptide]n+-fragmentome will increase the scores of peptide/protein identifications by MS/MS and thus will increase the fraction of automatically assigned MS/MS spectra in proteomics studies