| Summary: |
Event-related potential (ERP) abnormalities in patients with schizophrenia (SZ) have been reported since the seventies, with P50 gating, mismatch negativity and P3 reductions being the most recurrent findings [1].\nAn important auditory ERP component that has received little attention is the P2 (or P200). Some research groups, including ours, have found reduced P2 amplitude in patients with SZ [PP4]. Even if these results are consistent in showing P2 abnormalities, their value is still controversial given the existence of reports of augmented P2 [2] and null findings [3].\nOur previous studies of P2 in SZ converge with results from other laboratories in showing that this component may be fundamental for the electrophysiological characterization of these patients. It has been suggested that the P2 abnormalities may be specific to SZ and may be present in first degree relatives without criteria for SZ, thus constituting a putative endophenotype for this disorder [PP1,2]. Our previous and still on-going project [PP1] is testing this hypothesis.\nIn spite of these recent results, few studies have focused on this component since the mid 1980s. The relative lack of interest in the P2 may be due to the fact that it is poorly understood. Albeit being associated with SZ, little is known about its functional significance, making it difficult to integrate these findings into a neurocognitive model of information processing in SZ.\nThe study of the neural generators of P2 may elucidate not only its functional significance, but also the implications of the brain structural and functional abnormalities found in patients with SZ, which, to a significant extent, overlap with the putative generators for the P2 (e.g., [4]).\nA main difficulty in the study of the P2 is its contamination by earlier and later ERP components due to the voltage summation in the scalp, which has not been properly addressed in previous research. This may be overcome by designing an ERP paradigm that allo  |
Summary
Event-related potential (ERP) abnormalities in patients with schizophrenia (SZ) have been reported since the seventies, with P50 gating, mismatch negativity and P3 reductions being the most recurrent findings [1].\nAn important auditory ERP component that has received little attention is the P2 (or P200). Some research groups, including ours, have found reduced P2 amplitude in patients with SZ [PP4]. Even if these results are consistent in showing P2 abnormalities, their value is still controversial given the existence of reports of augmented P2 [2] and null findings [3].\nOur previous studies of P2 in SZ converge with results from other laboratories in showing that this component may be fundamental for the electrophysiological characterization of these patients. It has been suggested that the P2 abnormalities may be specific to SZ and may be present in first degree relatives without criteria for SZ, thus constituting a putative endophenotype for this disorder [PP1,2]. Our previous and still on-going project [PP1] is testing this hypothesis.\nIn spite of these recent results, few studies have focused on this component since the mid 1980s. The relative lack of interest in the P2 may be due to the fact that it is poorly understood. Albeit being associated with SZ, little is known about its functional significance, making it difficult to integrate these findings into a neurocognitive model of information processing in SZ.\nThe study of the neural generators of P2 may elucidate not only its functional significance, but also the implications of the brain structural and functional abnormalities found in patients with SZ, which, to a significant extent, overlap with the putative generators for the P2 (e.g., [4]).\nA main difficulty in the study of the P2 is its contamination by earlier and later ERP components due to the voltage summation in the scalp, which has not been properly addressed in previous research. This may be overcome by designing an ERP paradigm that allows the parametric manipulation of the P2 without affecting other components. This is the main objective of the present project.\nIn Phase 1 we propose to design an ERP paradigm, relying on what is known about N1-P2 responses to experimental manipulations, and identify which parameter will allow better discrimination of N1 and P2. High-density (128 channel) ERP data for the P2 obtained with this paradigm will be submitted to current density distribution estimation algorithms, determining which areas of the brain present activation patterns that covary with the manipulation. These foci are strong candidates to neural generators of the P2. To validate the current density solutions, covarying brain areas will serve as constraints for equivalent current dipole source modelling, by which the source solution that best fits the obtained scalp voltage will be found (overcoming the "garbage-in-garbage-out" problem of unrestricted solutions [5]).\nFor Phase 2, a paradigm that consistently differentiates P2 and N1 will be designed and used to collect ERP data from patients with SZ and healthy controls. The use of this paradigm will allow an uncontaminated comparison of the P2 in the two groups, elucidating what alterations are specific to it. Also, by following the same source estimation procedures as in Phase 1, the neural bases of the uncontaminated P2 can be studied in both groups.\nIn Phase 3, the paradigm from Phase 2 will be compared with a standard auditory oddball on the same subjects. Demonstration of correspondence of the P2 obtained with the different paradigms will warrant that our results can be compared with the existing literature, which relies mostly on oddball paradigms. These developments will support future evidence of the importance of P2 in the electrophysiological characterization of patients with SZ, as well as in determining electrophysiological endophenotypes for this disorder.\nThus, the following hypotheses are put forward, for each phase:\n- Phase 1:\n1. N1 and P2 components present different functions for the effects of the different parameters on their amplitude;\n2. N1 and P2 components present different neural sources, even if their generators are partially overlapped.\n-Phase 2:\n1. patients with SZ present reduced P2 amplitudes, independently of N1 amplitude;\n2. the reduced amplitude will further be reflected on reduced activation of the voxels corresponding to the P2-related areas of the current density distribution solution;\n3. the location of the neural generators for the P2 do not differ between-groups.\n-Phase 3:\n1. patients with SZ show smaller P2 amplitudes than controls on the oddball task;\n2. the reduced amplitude will be reflected on reduced activation of the voxels corresponding to P2-related areas of the current density distribution solution;\n3. the location of the neural generators for the standard oddball P2 do not differ between-groups;\n4. P2 components obtained with the different paradigms are correlated and their neural generators are similar. |