From semantics to feelings: how do individuals with schizophrenia rate the emotional valence of words?

Schizophrenia is characterized by both emotional and language abnormalities. However, in spite of reports of preserved evaluation of valence of affective stimuli, such as pictures, it is less clear how individuals with schizophrenia assess verbal material with emotional valence, for example, the overall unpleasantness/displeasure relative to pleasantness/attraction of a word. This study aimed to investigate how schizophrenic individuals rate the emotional valence of adjectives, when compared with a group of healthy controls. One hundred and eighty-four adjectives differing in valence were presented. These adjectives were previously categorized as “neutral,” “positive” (pleasant), or “negative” (unpleasant) by five judges not participating in the current experiment. Adjectives from the three categories were matched on word length, frequency, and familiarity. Sixteen individuals with schizophrenia diagnosis and seventeen healthy controls were asked to rate the valence of each word, by using a computerized version of the Self-Assessment Manikin (Bradley and Lang, 1994). Results demonstrated similar ratings of emotional valence of words, suggesting a similar representation of affective knowledge in schizophrenia, at least in terms of the valence dimension.This work was supported by a postdoctoral Grant (SFRH/ BPD/68967/2010) and by the PTDC/PSI-PCL/116626/2010 Grant from Fundação para a Ciência e a Tecnologia-FCT (Portugal) both awarded to A. P. Pinheiro., and by the National Institute of Mental Health-NIMH (RO1 MH 040799 grant awarded to R. W. McCarley.; RO3 MH 078036 grant awarded to M. Niznikiewicz)

Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Oscillatory electroencephalogram (EEG) abnormalities may reflect neural circuit dysfunction in neuropsychiatric disorders. Previously we have found positive correlations between the phase synchronization of beta and gamma oscillations and hallucination symptoms in schizophrenia patients. These findings suggest that the propensity for hallucinations is associated with an increased tendency for neural circuits in sensory cortex to enter states of oscillatory synchrony. Here we tested this hypothesis by examining whether the 40 Hz auditory steady-state response (ASSR) generated in the left primary auditory cortex is positively correlated with auditory hallucination symptoms in schizophrenia. We also examined whether the 40 Hz ASSR deficit in schizophrenia was associated with cross-frequency interactions.</p> <p>Sixteen healthy control subjects (HC) and 18 chronic schizophrenia patients (SZ) listened to 40 Hz binaural click trains. The EEG was recorded from 60 electrodes and average-referenced offline. A 5-dipole model was fit from the HC grand average ASSR, with 2 pairs of superior temporal dipoles and a deep midline dipole. Time-frequency decomposition was performed on the scalp EEG and source data.</p> <p>Results</p> <p>Phase locking factor (PLF) and evoked power were reduced in SZ at fronto-central electrodes, replicating prior findings. PLF was reduced in SZ for non-homologous right and left hemisphere sources. Left hemisphere source PLF in SZ was positively correlated with auditory hallucination symptoms, and was modulated by delta phase. Furthermore, the correlations between source evoked power and PLF found in HC was reduced in SZ for the LH sources.</p> <p>Conclusion</p> <p>These findings suggest that differential neural circuit abnormalities may be present in the left and right auditory cortices in schizophrenia. In addition, they provide further support for the hypothesis that hallucinations are related to cortical hyperexcitability, which is manifested by an increased propensity for high-frequency synchronization in modality-specific cortical areas.</p

Button-pressing affects P300 amplitude and scalp topography

Abstract Background: Scant and equivocal research exists examining the effects of button-pressing on P300. Button-pressing may decrease P300 latency and amplitude. The melding of motor potentials and P300 may also confound studies of P300 topography, such as studies of temporal scalp-area asymmetries in schizophrenia. Method: P300 was measured on button-press and silent-count tasks in control subjects. An estimate of motor activity was constructed from a simple reaction time task, with reaction times matched to the button-press task. The motor estimate was subtracted from the buttonpress P300 to assess Results: P300 was smaller and its topography different in the button-pressing task relative to silent-counting. The motor-correction procedure generated a P300 with normal topography. Comparison of the button-press P300 in controls to the silent-count P300 in schizophrenia patients reduced a signi®cant lateral asymmetry to trend level. This asymmetry was signi®cant after the correction procedure. Conclusions: Button-pressing generates smaller P300 than silent-counting. Also, P300 topography in button-pressing tasks is confounded by motor potentials. The distortion can be corrected with a motor potential estimate. Motor potentials can occlude differences in P300 topography between groups.

Amygdala–hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data

Evidence suggests that some structural brain abnormalities in schizophrenia are neurodevelopmental in origin. There is also growing evidence to suggest that shape deformations in brain structure may reflect abnormalities in neurodevelopment. While many magnetic resonance (MR) imaging studies have investigated brain area and volume measures in schizophrenia, fewer have focused on shape deformations. In this MR study we used a 3D shape representation technique, based on spherical harmonic functions, to analyze left and right amygdala-hippocampus shapes in each of 15 patients with schizophrenia and 15 healthy controls matched for age, gender, handedness and parental socioeconomic status. Left/right asymmetry was also measured for both shape and volume differences. Additionally, shape and volume measurements were combined in a composite analysis. There were no differences between groups in overall volume or shape. Left/right amygdala–hippocampal asymmetry, however, was significantly larger in patients than controls for both relative volume and shape. The local brain regions responsible for the left/right asymmetry differences in patients with schizophrenia were in the tail of the hippocampus (including both the inferior aspect adjacent to parahippocampal gyrus and the superior aspect adjacent to the lateral geniculate nucleus and more anteriorly to the cerebral peduncles) and in portions of the amygdala body (including the anterior–superior aspect adjacent to the basal nucleus). Also, in patients, increased volumetric asymmetry tended to be correlated with increased left/right shape asymmetry. Furthermore, a combined analysis of volume and shape asymmetry resulted in improved differentiation between groups. Classification function analyses correctly classified 70% of cases using volume, 73.3% using shape, and 87% using combined volume and shape measures. These findings suggest that shape provides important new information toward characterizing the pathophysiology of schizophrenia, and that combining volume and shape measures provides improved group discrimination in studies investigating brain abnormalities in schizophrenia. An evaluation of shape deformations also suggests local abnormalities in the amygdala–hippocampal complex in schizophrenia

Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated

Localized abnormalities in the cingulum bundle in patients with schizophrenia: A Diffusion Tensor tractography study

The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers connecting the isthmus of the cingulate with the parahippocampal cortex (I4). Furthermore, while FA in the I1 sub-connection was correlated with the severity of patients' positive symptoms (specifically hallucinations and delusions), FA in the I4 sub-connection was correlated with the severity of patients' negative symptoms (specifically affective flattening and anhedonia/asociality). These results support the notion that the CB is a conglomeration of structurally interconnected yet functionally distinct sub-connections, of which only a subset are abnormal in patients with schizophrenia. Furthermore, while acknowledging the fact that the present study only investigated the CB, these results suggest that the positive and negative symptoms of schizophrenia may have distinct neurobiological underpinnings

Shape abnormalities of caudate nucleus in schizotypal personality disorder

Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures

Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers

The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Speed of Processing, Attention/Vigilance, and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions

Interactions between mood and the structure of semantic memory: event-related potentials evidence

Recent evidence suggests that affect acts as modulator of cognitive processes and in particular that induced mood has an effect on the way semantic memory is used on-line. We used event-related potentials (ERPs) to examine affective modulation of semantic information processing under three different moods: neutral, positive and negative. Fifteen subjects read 324 pairs of sentences, after mood induction procedure with 30 pictures of neutral, 30 pictures of positive and 30 pictures of neutral valence: 108 sentences were read in each mood induction condition. Sentences ended with three word types: expected words, within-category violations, and between-category violations. N400 amplitude was measured to the three word types under each mood induction condition. Under neutral mood, a congruency (more negative N400 amplitude for unexpected relative to expected endings) and a category effect (more negative N400 amplitude for between- than to within-category violations) were observed. Also, results showed differences in N400 amplitude for both within- and between-category violations as a function of mood: while positive mood tended to facilitate the integration of unexpected but related items, negative mood made their integration as difficult as unexpected and unrelated items. These findings suggest the differential impact of mood on access to long-term semantic memory during sentence comprehension.The authors would like to thank to all the participants of the study, as well as to Jenna Mezin and Elizabeth Thompson for their help with data collection. This work was supported by a Doctoral Grant from Fundacao para a Ciencia e a Tecnologia - Portugal (SFRH/BD/35882/2007 to A. P. P.) and by the National Institute of Mental Health (RO1 MH 040799 to R. W. M.; RO3 MH 078036 to M.A.N.)