Sara Weinstein

Constrained Principal Component Analysis Reveals Functionally Connected Load-Dependent Networks Involved in Multiple Stages of Working Memory

Constrained principal component analysis (CPCA) with a finite impulse response (FIR) basis set was used to reveal functionally connected networks and their temporal progression over a multistage verbal working memory trial in which memory load was varied. Four components were extracted, and all showed statistically significant sensitivity to the memory load manipulation. Additionally, two of the four components sustained this peak activity, both for approximately 3 s (Components 1 and 4). The functional networks that showed sustained activity were characterized by increased activations in the dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, and left supramarginal gyrus, and decreased activations in the primary auditory cortex and “default network” regions. The functional networks that did not show sustained activity were instead dominated by increased activation in occipital cortex, dorsal anterior cingulate cortex, sensori‐motor cortical regions, and superior parietal cortex. The response shapes suggest that although all four components appear to be invoked at encoding, the two sustained‐peak components are likely to be additionally involved in the delay period. Our investigation provides a unique view of the contributions made by a network of brain regions over the course of a multiple‐stage working memory trial. Hum Brain Mapp, 2011.

Do you hear what I hear? Neural correlates of thought disorder during listening to speech in schizophrenia

Thought disorder is a fundamental symptom of schizophrenia, observable as irregularities in speech. It has been associated with functional and structural abnormalities in brain regions involved in language processing, including left temporal regions, during language production tasks. We were interested in the neural correlates of thought disorder during receptive language processing, as this function is relatively preserved despite relying on the same brain regions as expressive language. Twelve patients with schizophrenia and 11 controls listened to 30-s speech samples while undergoing fMRI scanning. Thought disorder and global symptom ratings were obtained for each patient. Thought disorder but not global symptomatology correlated positively with the BOLD response in the left posterior superior temporal lobe while listening to comprehensible speech (cluster-level corrected p=.023). The pattern of brain activity associated with thought disorder during listening to comprehensible speech differs from that seen during language generation tasks, where a reduction of the leftward laterality of language has often been observed. As receptive language is spared in thought disorder, we propose that the increase in activation reflects compensatory processing allowing for normal performance.

Does ketamine mimic aspects of schizophrenic speech

Speech disturbances are well-known symptoms contributing to the diagnosis of schizophrenia. Subanesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been reported to produce positive and negative symptoms and cognitive impairments consistent with those seen in schizophrenia. Insofar as this is true, it constitutes evidence that the NMDA system is involved in schizophrenia. It is therefore of interest to know whether ketamine produces speech disturbances like those of schizophrenia. Quantitative computer-aided analysis of apparently normal speech can detect clinically relevant changes and differences that are not noticeable to the human observer. Accordingly, in this study, speech samples were analysed for repetitiousness, idea density, and verb density using software developed by the authors. The samples came from two experiments, a within-subjects study of healthy volunteers given intravenous ketamine versus placebo, and a between-groups study of patients diagnosed with schizophrenia and comparable healthy controls. Our primary hypothesis was that in both schizophrenia and ketamine, repetitiousness wouLd increase, since perserverative speech is a well-known symptom of schizophrenia. Our secondary hypotheses were that in both schizophrenia and ketamine, idea density and verb density would decrease as indicators of cognitive impairment. The primary hypothesis was confirmed in the schizophrenia experiment (between groups) and the ketamine experiment (within subjects). The secondary hypotheses were disconfirmed except that in the ketamine experiment, verb density was significantly lowered. Reduced use of verbs apparently reflects a cognitive impairment of a different type than repetitiousness, and further investigation is needed to determine whether this impairment occurs in psychosis.

Brain activation mediates the association between structural abnormality and symptom severity in schizophrenia

Thought disorder is a symptom of schizophrenia expressed as disorganized or incoherent speech. Severity of thought disorder correlates with decreased left superior temporal gyrus grey matter volume and cortical activation in posterior temporal regions during the performance of language tasks. The goal of this study was to determine whether language-related activation mediates the association between thought disorder and left superior temporal lobe grey matter volume. 12 patients with schizophrenia were assessed for thought disorder. FMRI images were acquired for each subject while they listened to English speech, along with a high resolution structural image. Thought disorder was used as a covariate in the functional analysis to identify brain regions within which activation correlated with symptom severity. Voxel based morphometry was used to calculate grey matter volume of the planum temporale. A mediation model waste-tested using a four-step multiple regression approach incorporating cortical volume, functional activation and symptom severity. Thought disorder correlated with activation in a single cluster within the left posterior middle temporal gyrus during listening to speech. Grey matter volume within the planum temporale correlated significantly with severity of thought disorder and activation within the functional cluster. Regressing thought disorder on grey matter volume and BOLD response simultaneously led to a significant reduction in the correlation between grey matter volume and thought disorder. These results support the hypothesis that the association between decreased grey matter volume in the left planum temporale and severity of thought disorder is mediated by activation in the posterior temporal lobe during language processing.

Ketamine and schizophrenic speech: more difference than originally reported.

MA Covington CASPR, Artificial Intelligence Center, University of Georgia, Athens, GA, USA. WJ Riedel Department of Neuropsychology and Psychopharmacology, Faculty of Psychology, University of Maastricht, The Netherlands. C Brown CASPR, Artificial Intelligence Center, University of Georgia, Athens, GA, USA; H5, San Francisco, CA, USA. C He CASPR, Artificial Intelligence Center, University of Georgia, Athens, GA, USA. E Morris CASPR, Artificial Intelligence Center, University of Georgia, Athens, GA, USA. S Weinstein Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. J Semple CASPR, Artificial Intelligence Center, University of Georgia, Athens, GA, USA; GlaxoSmithKline Research & Development Ltd., Addenbrooke’s Hospital, Cambridge, UK. J Brown GlaxoSmithKline Research & Development Ltd., Addenbrooke’s Hospital, Cambridge, UK.

Positive schizotypy is not associated with speech abnormality

Aim: This study examined whether speech abnormalities typical of formal thought disorder in schizophrenia vary with the degree of positive schizotypy in the healthy population. We hypothesized that participants with high levels of positive schizotypy would show greater abnormality in speech relative to those with low levels of positive schizotypy.

Formal thought disorder in people at ultra-high risk of psychosis

Background Formal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear. Aims Examine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis. Method The Thought and Language Index (TLI) was used to assess 24 ultra-high-risk participants, 16 people with first-episode psychosis and 13 healthy controls. Ultra-high-risk individuals were followed up for a mean duration of 7 years (s.d.=1.5) to determine the relationship between formal thought disorder at baseline and transition to psychosis. Results TLI scores were significantly greater in the ultra-high-risk group compared with the healthy control group (effect size (ES)=1.2), but lower than in people with first-episode psychosis (ES=0.8). Total and negative TLI scores were higher in ultra-high-risk individuals who developed psychosis, but this was not significant. Combining negative TLI scores with attenuated psychotic symptoms and basic symptoms predicted transition to psychosis (P=0.04; ES=1.04). Conclusions TLI is beneficial in evaluating formal thought disorder in ultra-high-risk participants, and complements existing instruments for the evaluation of psychopathology in this group. Declaration of interests None. Copyright and usage

Street slang and schizophrenia

Young people often use language in an unconventional way. This may create communication difficulties for older doctors, particularly in the identification of disorganised speech, say Oliver D Howes and colleagues