Neurochemical regulation of auditory information processing studied with EEG/MEG: application to schizophrenia

Cognitive impairments of attention, memory and executive functions are a fundamental feature of the pathophysiology of schizophrenia. The neurophysiological and neurochemical changes in the auditory cortex are shown to underlie cognitive impairmentsin schizophrenia patients. Functional state of the neural substrate of auditory information processing could be objectively and non-invasively probed with auditory event-related potentials (ERPs) and event- related fields (ERFs). In the current work, we explored the neurochemical effect on the neural origins of auditory information processing in relation to schizophrenia. By means of ERPs/ERFs we aimed to determine how neural substrates of auditory information processing are modulated by antipsychotic medication in schizophrenia spectrum patients (Studies I, II) and by neuropharmacological challenges in healthy human subjects (Studies III, IV). First, with auditory ERPs we investigated the effects of olanzapine (Study I) and risperidone (Study II) in a group of patients with schizophrenia spectrum disorders. After 2 and 4 weeks of treatment, olanzapine has no significant effects on mismatch negativity(MMN) and P300, which, as it has been suggested, respectively reflect preattentive and attention-dependent information processing. After 2 weeks of treatment, risperidone has no significant effect on P300, however risperidone reduces P200 amplitude. This latter effect of risperidone on neural resources responsible for P200 generation could be partly explained through the action of dopamine. Subsequently, we used simultaneous EEG/MEG to investigate the effects of memantine (Study III) and methylphenidate (Study IV) in healthy subjects. We found that memantine modulates MMN response without changing other ERP components. This could be interpreted as being due to the possible influence of memantine through the NMDA receptors on auditory change- detection mechanism, with processing of auditory stimuli remaining otherwise unchanged. Further, we found that methylphenidate does not modulate the MMN response. This finding could indicate no association between catecholaminergic activities and electrophysiological measures of preattentive auditory discrimination processes reflected in the MMN. However, methylphenidate decreases the P200 amplitudes. This could be interpreted as a modulation of auditory information processing reflected in P200 by dopaminergic and noradrenergic systems. Taken together, our set of studies indicates a complex pattern of neurochemical influences produced by the antipsychotic drugs in the neural substrate of auditory information processing in patients with schizophrenia spectrum disorders and by the pharmacological challenges in healthy subjects studied with ERPs and ERFs.

Boundaries in Action : An Activity-theoretical Study of Development, Learning, and Change in Health Care Organization for Patients with Multiple and Chronic Illnesses

This study examines boundaries in health care organizations. Boundaries are sometimes considered things to be avoided in everyday living. This study suggests that boundaries can be important temporally and spatially emerging locations of development, learning, and change in inter-organizational activity. Boundaries can act as mediators of cultural and social formations and practices. The data of the study was gathered in an intervention project during the years 2000-2002 in Helsinki in which the care of 26 patients with multiple and chronic illnesses was improved. The project used the Change Laboratory method that represents a research assisted method for developing work. The research questions of the study are: (1) What are the boundary dynamics of development, learning, and change in health care for patients with multiple and chronic illnesses? (2) How do individual patients experience boundaries in their health care? (3) How are the boundaries of health care constructed and reconstructed in social interaction? (4) What are the dynamics of boundary crossing in the experimentation with the new tools and new practice? The methodology of the study, the ethnography of the multi-organizational field of activity, draws on cultural-historical activity theory and anthropological methods. The ethnographic fieldwork involves multiple research techniques and a collaborative strategy for raising research data. The data of this study consists of observations, interviews, transcribed intervention sessions, and patients' health documents. According to the findings, the care of patients with multiple and chronic illnesses emerges as fragmented by divisions of a patient and professionals, specialties of medicine and levels of health care organization. These boundaries have a historical origin in the Finnish health care system. As an implication of these boundaries, patients frequently experience uncertainty and neglect in their care. However, the boundaries of a single patient were transformed in the Change Laboratory discussions among patients, professionals and researchers. In these discussions, the questioning of the prevailing boundaries was triggered by the observation of gaps in inter-organizational care. Transformation of the prevailing boundaries was achieved in implementation of the collaborative care agreement tool and the practice of negotiated care. However, the new tool and practice did not expand into general use during the project. The study identifies two complementary models for the development of health care organization in Finland. The 'care package model', which is based on productivity and process models adopted from engineering and the 'model of negotiated care', which is based on co-configuration and the public good.