Mapping reflexive shifts of attention in eye-centered and hand-centered coordinate systems.

Behavioral studies indicate that directional gaze and hand pointing are fundamental social signals that may capture spatial attention more powerfully than directional arrows. By using fMRI, we explored whether reflexive shifts of attention triggered by different distracters were influenced by the motor effector used for performing an overt response. In separate blocks, healthy participants performed a directional saccadic or a hand pointing movement. Color changes of a central black fixation point constituted the imperative instruction signal to make a leftward (red color) or a rightward (blue color) movement while ignoring distracting leftward or rightward oriented gaze, hand pointing, or arrow. Distracters that were directionally incongruent with the instruction cue impaired the saccadic and pointing-release RTs. The comparison of incongruent vs. congruent conditions showed an increase of BOLD signal in the frontal eye field (FEF), the intraparietal sulcus (IPS), and the posterior parietal cortex (PPC) bilaterally. Importantly, a specific relationship between distracter and effector used for the response was found in these frontal and parietal regions. In particular, higher activity in the FEF, for distracting gaze was found mainly during the saccadic response task. In the same vein, higher activity in the left and right IPS regions was found for the distracting hand mainly in the hand pointing task. The results suggest that reflexive shifts of attention triggered by social signals are coded in the fronto-parietal cortex according to effector-specific mapping rules

A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses

The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation

Deficient sustained attention to response task and P300 characteristics in early Huntington’s disease

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington’s disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group