Person:

McCarley, Robert William

Both facial expression and tone of voice represent key signals of emotional communication but their brain processing correlates remain unclear. Accordingly, we constructed a novel implicit emotion recognition task consisting of simultaneously presented human faces and voices with neutral, happy, and angry valence, within the context of recognizing monkey faces and voices task. To investigate the temporal unfolding of the processing of affective information from human face-voice pairings, we recorded event-related potentials (ERPs) to these audiovisual test stimuli in 18 normal healthy subjects; N100, P200, N250, P300 components were observed at electrodes in the frontal-central region, while P100, N170, P270 were observed at electrodes in the parietal-occipital region. Results: indicated a significant audiovisual stimulus effect on the amplitudes and latencies of components in frontal-central (P200, P300, and N250) but not the parietal occipital region (P100, N170 and P270). Specifically, P200 and P300 amplitudes were more positive for emotional relative to neutral audiovisual stimuli, irrespective of valence, whereas N250 amplitude was more negative for neutral relative to emotional stimuli. No differentiation was observed between angry and happy conditions. The results suggest that the general effect of emotion on audiovisual processing can emerge as early as 200 msec (P200 peak latency) post stimulus onset, in spite of implicit affective processing task demands, and that such effect is mainly distributed in the frontal-central region.

As cigarette smoking prevalence rates approach 90% in schizophrenia, an important emerging question is the role of nicotine in the disease-related disturbance in cognition. We therefore tested a total of 38 male cigarette smokers (22 schizophrenia, 16 normal control), matched on nicotine dependence, on the Attention Network Test (ANT) at three nicotine conditions (baseline, 8hr overnight withdrawal, 3hr 21mg nicotine patch). The results indicated that the groups did not differ in performance on either of three ANT measures (alertness, orienting, and executive) across baseline, patch, and withdrawal conditions. However, in comparison to the controls, the participants with schizophrenia showed faster ANT reaction time (RT) for the nicotine patch in relation to the baseline condition. In comparison to controls, the participants with schizophrenia also showed reduced ANT accuracy at withdrawal but not at patch condition. These results suggest that overall processing speed and accuracy are affected differently by nicotine levels in participants with schizophrenia, with evidence supporting greater impairment from withdrawal and greater improvement from nicotine administration.

Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card SortingTest, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F1,47=17.4, P= 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F1,47=19.2, P<0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (χ2=12.49, P= 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse `positive formal thought disorder' (r=−0.638, P= 0.001), and a smaller right MiOG with a longer duration of the illness (r=−0.618, P= 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r=0.541, P= 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r=−0.608, P= 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.

We sought to identify the functional correlates of reduced magnetic resonance imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative symptoms, and neuropsychological tests of facial memory and executive functioning were examined within the same subjects. The results indicated two distinct, dissociable brain structure-function relationships: (1) reduced left STG volume-positive symptoms-executive deficits; (2) reduced left FG-negative symptoms-facial memory deficits. STG and FG volume reductions may each make distinct contributions to symptoms and cognitive deficits of schizophrenia.

Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. We used measures of phase locking and phase coherence in the scalp-recorded electroencephalogram to examine the synchronization of neural circuits in schizophrenia. Compared with matched control subjects, schizophrenia patients demonstrated: (1) absence of the posterior component of the early visual gamma band response to Gestalt stimuli; (2) abnormalities in the topography, latency, and frequency of the anterior component of this response; (3) delayed onset of phase coherence changes; and (4) the pattern of anterior–posterior coherence increases in response to Gestalt stimuli found in controls was replaced by a pattern of interhemispheric coherence decreases in patients. These findings support the hypothesis that schizophrenia is associated with impaired neural circuitry demonstrated as a failure of gamma band synchronization, especially in the 40 Hz range.

Objective: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. Method: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. Results: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. Conclusions: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

We view schizophrenia as producing a failure of attentional modulation that leads to a breakdown in the selective enhancement or inhibition of semantic/lexical representations whose biological substrata are widely distributed across left (dominant) temporal and frontal lobes. Supporting behavioral evidence includes word recall studies that have pointed to a disturbance in connectivity (associative strength) but not network size (number of associates) in patients with schizophrenia. Paralleling these findings are recent neural network simulation studies of the abnormal connectivity effect in schizophrenia through ‘lesioning’ network connection weights while holding constant network size. Supporting evidence at the level of biology are in vitro studies examining N-methyl-d-aspartate (NMDA) receptor antagonists on recurrent inhibition; simulations in neural populations with realistically modeled biophysical properties show NMDA antagonists produce a schizophrenia-like disturbance in pattern association. We propose a similar failure of NMDA-mediated recurrent inhibition as a candidate biological substrate for attention and semantic anomalies of schizophrenia.

Objective: Few studies have evaluated the parietal lobe in schizophrenia despite the fact that it has an important role in attention, memory, and language—all functions that have been reported to be abnormal in schizophrenia. The inferior parietal lobule, in particular, is of interest because it is not only part of the heteromodal association cortex but also is part of the semantic-lexical network, which also includes the planum temporale. Both the inferior parietal lobule, particularly the angular gyrus of the inferior parietal lobule, and the planum temporale are brain regions that play a critical role as biological substrates of language and thought. The authors compared volume and asymmetry measures of the individual gyri of the parietal lobe by means of magnetic resonance imaging (MRI) scans. Method: MRI scans with a 1.5-Tesla magnet were obtained from 15 male chronic schizophrenic and 15 comparison subjects matched for age, gender, and parental socioeconomic status. Results: Inferior parietal lobule volumes showed a leftward asymmetry (left 7.0% larger than right) in comparison subjects and a reversed asymmetry (left 6.3% smaller than right) in schizophrenic subjects. The angular gyrus accounted for this difference in asymmetry, with the left angular gyrus being significantly larger (18.7%) than the right in comparison subjects, a finding that was not observed in schizophrenic patients. A further test of angular gyrus asymmetry showed a reversal of the normal left-greater-than-right asymmetry in the schizophrenic patients. Conclusions: Patients with schizophrenia showed a reversed asymmetry in the inferior parietal lobule that was localized to the angular gyrus, a structure belonging to the heteromodal association cortex as well as being part of the semantic-lexical network. This finding contributes to a more comprehensive understanding of the neural substrates of language and thought disorder in schizophrenia.

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.

Background—Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. Aims—To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named ShapeNormalized Dispersion (SHD). Methods—DTIs (3T, 51 gradient directions, 1.7 mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. Results—The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. Conclusions—The results suggest that the transcallosal misconnectivity believed to be associated with schizophrenia could arise from abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by irregularities in the normative processes of neurodevelopment.