Kate McClannahan

Classification of schizophrenia with spectro-temporo-spatial MEG patterns in working memory.

OBJECTIVE To investigate whether temporo-spatial patterns of brain oscillations extracted from multichannel magnetoencephalogram (MEG) recordings in a working memory task can be used successfully as a biometric marker to discriminate between healthy control subjects and patients with schizophrenia. METHODS Five letters appearing sequentially on a screen had to be memorized. The letters constituted a word in one condition and a pronounceable non-word in the other. Power changes of 248 channel MEG data were extracted in frequency sub-bands and a two-step filter and search algorithm was used to select informative features that discriminated patients and controls. RESULTS The discrimination between patients and controls was greater in the word condition than in the non-word condition. Furthermore, in the word condition, the most discriminant patterns were extracted in delta (1-4 Hz), alpha (12-16 Hz) and beta (16-24 Hz) frequency bands. These features were located in the left dorso-frontal, occipital and left fronto-temporal, respectively. CONCLUSION The analysis of the oscillatory patterns of MEG recordings in the working memory task provided a high level of correct classification of patients and controls. SIGNIFICANCE We show, using a newly developed algorithm, that the temporo-spatial patterns of brain oscillations can be used as biometric marker that discriminate schizophrenia patients and healthy controls.

Evaluation of speech misattribution bias in schizophrenia.

BACKGROUND The attribution of self-generated speech to others could explain the experience of verbal hallucinations. To test this hypothesis, we developed a task to simultaneously evaluate (A) operations of self-other distinction and (B) operations that have the same cognitive demands as in A apart from self-other distinction. By adjusting A to B, operations of self-other distinction were specifically evaluated. METHOD Thirty-nine schizophrenia patients and 26 matched healthy controls were required to distinguish between self-generated, other-generated and non-generated (self or other) sentences. The sentences were in the first, second or third person and were read in a male or female voice in equal proportions. Mixed multi-level logistic regression models were used to investigate the effect of group, sentence source, pronoun and gender of the heard sentences on response accuracy. RESULTS Patients differed from controls in the recognition of self-generated and other-generated sentences but not in general recognition ability. Pronoun was a significant predictor of response accuracy but without any significant interaction with group. Differences in the gender of heard sentences were not significant. Misattribution bias differentiated groups only in the self-other direction. CONCLUSIONS These data support the theory that misattribution of self-generated speech to others could result in verbal hallucinations. The syntactic (pronoun) factor could impact self-other distinction in subtypes of verbal hallucinations that are phenomenologically defined whereas the acoustic factor (gender of heard speech) is unlikely to affect self-other distinction.

Temporospatial Characterization of Brain Oscillations (TSCBO) Associated with Subprocesses of Verbal Working Memory in Schizophrenia

The studies of the neural correlates of verbal working memory in schizophrenia are somewhat inconsistent. This could be related to experimental paradigms that engage differentially working memory components or methodological limitations in terms of characterization of brain activity. Magnetoencephalographic recordings were obtained on 10 schizophrenia patients and 11 healthy controls while performing a modified Sternberg paradigm to investigate subprocesses of verbal working memory. A new method for temporospatial characterization of brain oscillations was applied to whole head recordings and a 1–48 Hz frequency range. Patients differed from controls in event-related synchronization/desynchronization (ERS/ERD) patterns during the encode phase, the mid-maintain phase, and the end of the maintain phase. During the encode phase, patients did not show 1–4 Hz ERS in the left anterior frontal and left parietal lobes. In the mid-maintain phase, the left anterior frontal and left parietal lobes 1–4 Hz ERS, and the bilateral occipital lobes 8–32 Hz ERS were not observed in patients. At the end of the maintain phase, patients did not exhibit 12–48 Hz ERD in the left frontal and parietal lobes. The behavioral data showed reduced primacy effect In schizophrenia, the encode and maintain subprocesses were associated with less ERS and less ERD, respectively. These ERS/ERD abnormalities had specificity in terms of frequency and spatial location. Less ERD reflects reduced complexity of the neural activity, while reduced ERS reflects failure of the neural systems to resume idle state. The impaired primacy effect appears related to specific ERS/ERD patterns in the encode and maintain phases.

The temporal, spatial, and frequency dimensions of neural oscillations associated with verbal working memory

Cognitive operations engage neural generators oscillating at different frequencies distributed in time and space. Accordingly, oscillatory activity detected by magnetoencephalography (MEG)/electroencephalography (EEG) should be analyzed along frequency, time, and spatial dimensions. MEG data were obtained from 19 healthy individuals while performing a modified Sternberg paradigm. The stimuli were letters, which constituted words or pronounceable nonwords. We applied tridimensional analysis of oscillations and also computed event-related fields (ERFs) in areas where significant changes in oscillatory activity were observed. Verbal working memory for visual verbal stimuli was associated with oscillatory interplay between the bilateral occipital lobes and the left frontoparietotemporal areas. Spatially stable occipital desynchrony was noted during information encoding, while a left hemisphere desynchronization, increasing in amplitude and spatial extent over time, was observed during information encoding and maintenance. No ERF changes were detected during information maintenance. Oscillatory activity associated with verbal working memory is consistent with the above hypothesis. These findings underscore the importance of multidimensional evaluation of oscillations. The findings also indicate that combining electrophysiological methods increase the chance of signal detection.

Neural oscillations associated with the primacy and recency effects of verbal working memory

For sequential information, the first (primacy) and last (recency) items are better remembered than items in the middle of the sequence. The cognitive operations and neural correlates for the primacy and recency effects are unclear. In this paper, we investigate brain oscillations associated with these effects. MEG recordings were obtained on 19 subjects performing a modified Sternberg paradigm. Correlation analyses were performed between brain oscillatory activity and primacy and recency indices. Oscillatory activity during information maintenance, not encoding, was correlated with the primacy and recency effects. The primacy effect was associated with occipital post-desynchrony, and temporal post-synchrony. The recency effect was associated with parietal and temporal desynchrony. Differences were also observed according to the maintenance strategy. These data indicate that the primacy and recency effects are related to different neural, and likely cognitive, operations that are dependant on the strategy for information maintenance.

Schizophrenia Classification using Working Memory MEG ERD/ERS Patterns

In this paper we investigate the use of event related desynchronization (ERD) and synchronization (ERS) patterns extracted from magnetoencephalogram (MEG) in a working memory task to discriminate between controls and patients with schizophrenia. In the experimental paradigm, sequential letters appearing on a screen are memorized by subjects. In one of two conditions the letters constituted a word. The ERD and ERS patterns are extracted in the theta, alpha, beta and gamma bands from 248 electrode locations covering the whole head. We noticed that most of the ERD patterns are localized on the left frontotemporal area in both word and nonword conditions in the late memorization stage. The beta band showed the most significant difference in this cortical area between controls and schizophrenia patients. By using a decision tree, 94.7% and 87.5% classification accuracy was obtained for controls and patients individually in both word and nonword conditions. Furthermore, we report that on the left frontotemporal lobe, the discrimination within the beta band between patients and controls in the word condition was higher than in the nonword condition. The higher discrimination within the word condition can be linked to the abnormalities in language processing in schizophrenia patients. Our results show that the ERD/ERS patterns extracted from MEG can be successfully used in patient-control discrimination with appropriate adjustment of spatial, spectral, temporal and functional process parameters

S12-4 Oscillatory activity associated with information encoding and maintenance in schizophrenia

not available at time of printing. S12-4 Oscillatory activity associated with information encoding and maintenance in schizophrenia M. Stephane1,2, M. Kuskowski1,2, K. McClannahan1 1Psychiatry Service line, VA Medical Center, Minneapolis, MN, 2Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA Objective: To the extent that EEG/MEG signals represent the sum of activity of neural generators oscillating at different frequencies and distributed in time and space, brain oscillations should be investigated along the frequency, time, and spatial dimensions concomitantly. In this paper, we apply methodology for temporo-spatial investigation of oscillatory activity associated with the encoding and maintenance processes of verbal working memory in schizophrenia. Methods: Magnetoencephalographic recordings were obtained while schizophrenia patients and matched healthy controls performed a Sternberg paradigm. Subjects viewed sets of five letters appearing sequentially on the screen. After a delay, they had to decide whether a probe letter was included in the set or not. Brain oscillatory activity was evaluated along the space, time and frequency dimensions combined. Results: Patients differed from controls in event related synchronization/desynchronization (ERD/ERS) patterns during the encode phase, the mid-maintain phase, and the end of the maintain phase. During the encode phase, ERS in 1 4 Hz band in the left anterior frontal and left parietal lobes was not observed in patients. In the mid-maintain phase, ERS in 1 4 Hz band in the left anterior frontal and left parietal lobes, and ERS in 8 32 Hz band in the bilateral occipital lobes were not observed in patients. At the end of the maintain phase, patients did not exhibit 12 48 Hz ERD in the left frontal and parietal lobes. Conclusion: In schizophrenia, the encode and maintain processes of working memory were associated with reduced ERS and reduced ERD, respectively. These ERD/ERS abnormalities had specificity in terms of frequency and spatial location. The reduced ERS could reflect abnormal encoding and failure of the neural systems to resume idle state after the encoding operations. The reduced ERD could be related to less complex neural activity during online information maintenance. S12-5 Mismatch negativity: a physiological index of functional and structural brain abnormalities in schizophrenia P.T. Michie1 1Centre for Brain and Mental Health Research, School of Psycholoyg, University of Newcastle, Callaghan, Australia MMN is an ERP generated when the auditory system detects a deviant sound in a regular sequence of sounds. It is a frontal negative deflection with a peak latency around 50 to 100 ms after deviance is detectable. MMN results from an automatic memory based comparison process that detects a discrepancy between the neural representation of the

S2-3 Online information maintenance and impaired primacy effedct in schizophrenia

Results: In EMG, 10/11 OSAS patients had typical findings indicating motor neuropathy. Mild-moderate pathological findings were present in 12/22 snorers. EMG was normal in 10/10 non-snoring subjects. At the tonsillar pillars, there were significant differences in both vibration and cold thresholds between normals and OSAS-patients. Vibration thresholds were not significantly different between snorers and normals, but they differed concerning cold detection. CDT was easier to test with low variability in normal subjects. Vibration thresholds exhibited considerable variability; two normal subjects could not detect vibrations. Thresholds at other locations showed no group differences. Conclusions: In snorers, 35% had signs of sensory nervous lesions and 54% of motor nervous lesions. In OSAS-patients, 78% had signs of sensory nervous lesions and 91% of motor nervous lesions. This supports the hypothesis of a progressive oropharyngeal nervous lesion in OSAS. CDT gave more discriminative results than vibration, and is non-invasive and painless in contrast to needle-EMG. It is therefore recommended as a useful clinical method to evaluate the degree of sensory damage. It might also predict whether a snoring patient will develop OSAS, and should therefore receive active treatment.