Factors in sensory processing of prosody in schizotypal personality disorder: an fMRI experiment.

INTRODUCTION: Persons diagnosed with schizophrenia demonstrate deficits in prosody recognition. To examine prosody along the schizophrenia spectrum, antipsychotic-naïve schizotypal personality disorder (SPD) subjects and healthy control subjects were compared. It was hypothesized that SPD subjects would perform more poorly; with cognitive and demographic factors contributing to the poor performance. The superior temporal gyrus (STG) was selected as the region-of-interest (ROI) given its known abnormalities in SPD and its important role in the processing of prosody. METHODS: SPD and healthy comparison (HC) subjects were matched on age, IQ, and parental social-economic status (PSES). Cognitive measures included the Speech Sound Perception Test (SSPT) to examine phonological processing (SPD=68, HC=74) and the Verbal Fluency task to examine executive functioning (SPD=129, HC=138). The main experiment was a novel fMRI task of prosody identification using semantically neutral sentences spoken with emotional prosody (SPD=16, HC=13). Finally, volumetric measurement of the superior temporal sulcus (STS), a key region for processing prosody, and partially overlapping with the STG, was performed (SPD=30, HC=30). RESULTS: Phonological processing and executive functioning were both impaired in SPD subjects compared with HC subjects. Contrary to the prediction, SPD subjects, as a group, were similar to HC subjects in terms of correctly indentifying the emotion conveyed and reaction time. Within the SPD group, prosody identification accuracy was influenced by executive functioning, IQ and perhaps PSES, relationships not found with HC subjects. Phonological perception aided prosody identification in both diagnostic groups. As expected, both groups activated the STG while performing the prosody identification task. However, SPD subjects may have been less "efficient" in their recruitment of STG neurons. Finally, SPD subjects demonstrated a trend toward smaller STS volumes on the left, particularly the lower bank. CONCLUSIONS: These data suggest that subtle differences between SPD and controls in phonological processing, executive functioning, IQ, and possibly PSES, contributed to difficulty in processing prosody for some SPD subjects.

Dichotic listening in schizotypal personality disorder: evidence for gender and laterality effects.

Verbal dichotic listening performance was examined in 42 right-handed men and women with DSM-IV-defined schizotypal personality disorder (SPD) and 68 right-handed controls. As expected, both male and female control groups showed a right ear advantage on a verbal dichotic listening task. Although SPD subjects in general had lower accuracy scores than comparison subjects, only male SPD subjects showed an abnormal left ear advantage that was specifically due to deficient right ear performance. The results suggest that left hemisphere temporal lobe structures may be particularly involved in male, but not female, SPD.

Abnormal pitch mismatch negativity in individuals with schizotypal personality disorder.

BACKGROUND: The goal of the study was to examine mismatch negativity (MMN) in schizotypal personality disorder (SPD) individuals. Abnormal MMN has been a consistent finding in chronic schizophrenia and there also have been reports of reduced duration MMN in first episode schizophrenia patients [Umbricht, D., Krljes, S., Mismatch negativity in schizophrenia: a meta-analysis. Schizophrenia Research (2005); 76(1):1-23], with some studies finding no pitch MMN amplitude differences [Salisbury, D.F., Shenton, M.E., Griggs, C.B., Bonner-Jackson, A., McCarley, R.W., Mismatch negativity n chronic schizophrenia and first-episode schizophrenia. Archives of General Psychiatry (2002); 59(8):686-694.], while others reporting a modest reduction [Umbricht, D.S., Bates, J.A., Lieberman, J.A., Kane, J.M., Javitt, D.C., Electrophysiological indices of automatic and controlled auditory information processing in first-episode, recent-onset and chronic schizophrenia. Biological Psychiatry (2006); 59(8):762-772], in recent onset schizophrenia patients. To our knowledge no reports exist of MMN in SPD individuals. METHODS: Twenty six normal (14 females) control and 23 SPD (12 females) individuals were tested using the pitch MMN paradigm. Normal control (NC) and SPD individuals were recruited from the general population and assessed using DSM-IV. SPD individuals were included if they met 5 or more criteria for SPD disorder. The subjects listened to 2000 frequent 1 kHz pure tones and 100 rare 1.2 kHz pure tones while reading a magazine article. MMN was measured from a difference waveform within the latency window of 175-276 ms. RESULTS: Reduced MMN amplitude was found in SPD relative to NC subjects (p<0.045). CONCLUSIONS: These results point to potential differences between SPD and schizophrenia, where no reduction in MMN was found in most studies of first episode patients.

Functional asymmetry in human primary auditory cortex: identified from longitudinal fMRI study.

The leftward hemispheric dominance in language processing may be associated with fundamental functional asymmetry in the primary auditory cortex (PAC). Based on repeated functional MRI (fMRI) measurements, we investigated the presence of functional asymmetry in the human PAC using binaural presentation of linguistic sounds (two-syllable nouns) and simple tonal stimulation. Eight right-handed volunteers underwent nine fMRI sessions, approximately eight weeks apart, spanning the duration of more than a year. The PAC from each hemisphere was manually segmented and the volume of activation, detected within the segmented region-of-interest, was measured across the subjects and sessions to generate functional laterality indices. Although variations existed in activation volume between sessions and subjects, we found predominant and consistent leftward functional asymmetry in PAC during both linguistic and non-linguistic sound stimulations.

Long-term reproducibility analysis of fMRI using hand motor task.

This article reports test-retest reproducibility of functional MRI (fMRI) measurement on brain activation elicited by auditory-cued sequential finger tapping. Eight right-handed volunteers participated in nine fMRI sessions, approximately eight weeks apart, for the duration of more than a year. The first scan session was repeated within a day to examine the intra-session reproducibility. The frequency of activation for neural substrates relevant to the task was constructed across the subjects and sessions. The spatial reproducibility was measured as the ratio of the size of the volume as well as its overlaps with respect to the first scan session from regions-of-interest in the selected motor circuitry. Consistent activation patterns between sessions and across subjects were observed in the sensorimotor areas such as the left primary, supplementary, and premotor areas, as well as in the right cerebellar areas without evidence of session-dependent trends. Quantitative analysis showed that the reproducibility measures varied within the range obtained from studies on fMRI reproducibility covering much shorter terms. Intra-session fMRI scans yielded slightly better reproducibility measures compared to the results obtained from other scan sessions. The findings suggest that the reproducible fMRI measurement can be obtained for long-term monitoring of brain function.

Functional MRI of auditory verbal working memory: long-term reproducibility analysis.

Although functional MRI (fMRI) has shown to be a tool with great potential to study the normal and diseased human brain, the large variability in the detected hemodynamic responses across sessions and across subjects hinders a wider application. To investigate the long-term reproducibility of fMRI activation of verbal working memory (WM), eight normal subjects performed an auditory version of the 2-back verbal WM task while fMRI images were acquired. The experiment was repeated nine times with the same settings for image acquisition and fMRI task. Data were analyzed using SPM99 program. Single-session activation maps and multi-subject session-specific activation maps were generated. Regions of interest (ROIs) associated to specific components of verbal WM were defined based on the voxels' coordinates in Talairach space. Visual observation of the multi-subject activation maps showed similar activation patterns, and quantitative analysis showed small coefficients of variance of activation within ROIs over time, suggesting small longitudinal variability of activation. Visual observation of the activation maps of individual sessions demonstrated striking variation of activation across sessions and across subjects, and quantitative analysis demonstrated larger contribution from between-subject variation to overall variation than that from within-subject variation. We concluded that by multi-subject analysis of data from a relatively small number of subjects, reasonably reproducible activation for the 2-back verbal WM paradigm can be achieved. The level of reproducibility encourages the application of this fMRI paradigm to the evaluation of cognitive changes in future investigations. The quantitative estimation of the proportions of within-subject and between-subject variabilities in the overall variability may be helpful for the design of future studies.

A MRI study of fusiform gyrus in schizotypal personality disorder.

The fusiform gyrus is important for face and object recognition, is abnormal in schizophrenia, but has not been studied in schizotypal personality disorder (SPD). Thin-slice MR images showed no differences, either in right, left or total fusiform gyri volumes, between subjects with SPD (N=21) and normal controls (N=19). However, there was a correlation between severity of illusions and magical thinking suffered by the SPD subjects and smaller right fusiform gyrus volumes. This suggests that future studies may be useful in determining the functional competence of this gyrus in SPD.