This doctoral thesis focuses on brain activity in response to proprioceptive stimulation in schizophrenia. The works encompass methodological developments substantiated by investigations of healthy volunteers and two clinical studies of schizophrenia spectrum patients. American psychiatrist Sandor Rado (1890-1972) suggested that one of two un-reducible deficits in schizophrenia was a disorder of proprioception. Exploration of proprioceptive information processing is possible through the measurement of evoked and event related potentials. Event related EEG can be analyzed as conventional time-series averages or as oscillatory averages transformed into the frequency domain. Gamma activity evoked by electricity or by another type of somatosensory stimulus has not been reported before in schizophrenia. Gamma activity is considered to be a manifestation of perceptual integration. A new load stimulus was constructed that stimulated the proprioceptive dimension of recognition of applied force. This load stimulus was tested both in simple and several types of more complex stimulus paradigms, with and without tasks, in total in 66 healthy volunteers. The evoked potential (EP) resulting from the load stimulus was named the proprioceptive EP. The later components of the proprioceptive EP (> 150 ms) were modulated similarly to previously reported electrical somatosensory EPs by repetition and cognitive task. The earlier activity was further investigated through decomposition of the time-frequency transformed data by a new non-negative matrix analysis, and previous research and visual inspection validated these results. Several time-frequency components emerged in the proprioceptive EP. The contra-lateral parietal gamma component (60-70 ms; 30-41 Hz) had not previously been described in the somatosensory modality without electrical stimulation. The parietal beta component (87-103 ms; 19-22 Hz) was increased when the proprioceptive stimulus appeared in a predictable sequence in several runs of recording. Although the experimental paradigm had inherent confounders, it was suggested that the increase observed in the predictable situation, in healthy subjects, was due to priming of the somatosensory cortex through top-down modulation. The proprioceptive EP was investigated in two different samples of a total of 30 schizophrenia spectrum patients. The left contra-lateral parietal cortical activity 60-120 ms following the load stimulus was affected in both samples. In the first experiment a delay was observed and in the second experiment diminished amplitude and trial-to-trial phase consistency of high frequency (18-45 Hz) activity. Both effects were interpreted as a consequence of diminished precision of activation of the left somatosensory cortex and it was suggested to be in accordance with two theories of schizophrenic information processing: the theory of deficiency of corollary discharge and the theory of weakening of the influence of past regularities. No gating deficiency was observed and the imprecision and amplitude attenuation was not a general phenomenon across the entire brain response. Summing up, in support of Rado's hypothesis, schizophrenia spectrum patients demonstrated abnormalities in proprioceptive information processing. Future work needs to extend the findings in larger un-medicated, non-chronic, patient samples and investigate the connection between schizophrenic symptoms, perception and attenuation of the proprioceptive EP.
|Bidragets oversatte titel||Proprioceptiv informationsbearbejdning ved skizofreni|