L. Decker

Subjective rating of emotionally salient stimuli modulates neural activity.

Studies using emotionally salient stimuli have demonstrated neural activation in limbic and paralimbic brain regions. In some studies, subjects passively perceive evocative stimuli, while in other studies, they perform specific cognitive tasks. Evidence is emerging that even a simple cognitive task performed on emotionally salient stimuli can affect neural activation in emotion-associated brain regions. We tested the hypothesis that rating the subjective experience of an aversive visual stimulus would decrease limbic/paralimbic activation and increase activity in medial frontal regions. Ten healthy subjects underwent (15)O PET scans while they viewed pictures of aversive (AV) and nonaversive (NA) content, taken from the International Affective Picture System. Subjects appraised pictures on a scale of pleasantness/unpleasantness during one set of scans (RTNG), and they passively viewed pictures during another set (PSVW). After each scan, emotional responses were assessed. RTNG was associated with significantly less intensity of sadness and significantly less activation (AV - NA) of the right insula/amygdala and left insula, relative to PSVW. RTNG also activated the dorsal medial prefrontal cortex and the anterior cingulate sulcus, which were not differentially activated during PSVW. For both RTNG and PSVW, subjects activated the left fusiform gyrus. The results support the proposition that task instructions about how subjects should process evocative stimuli can affect neural activity.

Activation of the medial prefrontal cortex and extended amygdala by individual ratings of emotional arousal: a fMRI study

BACKGROUND Significant differences between individual responses to emotional stimuli can be important for the study of emotion. We investigated whether incorporating individual ratings of emotional arousal in the analysis of functional magnetic resonance imaging (fMRI) data improves the detection of activation in the medial prefrontal cortex (MPFC) and sublenticular extended amygdala (SLEA), areas implicated in the processing of emotional salience. METHODS Healthy subjects viewed counterbalanced blocks of aversive, nonaversive, and blank images. Outside the scanner, they rated the intensity of emotional arousal (salience) of each presented picture. RESULTS Incorporating the subjects response to each stimulus by using individualized regressors produced more robust activations within MPFC and SLEA compared with a simple boxcar regressor, identical for all subjects. CONCLUSIONS Our findings demonstrate that individual behavioral data are useful in improving detection of activation in block-design functional imaging studies.

The Effect of Emotional Content on Visual Recognition Memory: A PET Activation Study

The emotional content of stimuli can enhance memory for those stimuli. This process may occur via an interaction with systems responsible for perception and memory or via the addition of distinct brain regions specialized for emotion which augment mnemonic processing. We performed an 15O PET study to identify neuroanatomical systems which encode visual stimuli with strong negative emotional valence compared to stimuli with neutral valence. Subjects also performed a recognition memory task for these same images, mixed with distracters of similar emotional valence. The experimental design permitted us to independently test effects of emotional content and recognition memory on regional activity. We found activity in the left amygdaloid complex associated with the encoding of emotional stimuli, although this activation appeared early in the scanning session and was not detectable during recognition memory. Visual recognition memory recruited the right middle frontal gyrus and the superior anterior cingulate cortex for both negative and neutral stimuli. An interaction occurred between emotional content and recognition in the lingual gyrus, where greater activation occurred during recognition of negative images compared to recognition of neutral images. Instead of distinct neuroanatomical systems for emotion augmenting memory, we found that emotionally salient stimuli appeared to enhance processing of early sensory input during visual recognition.

A functional anatomic study of emotion in schizophrenia.

Using salient pictures with aversive (AV) and non-aversive (NA) content, we probed limbic-emotional function in schizophrenia, testing specific hypotheses that the amygdala would exhibit abnormal activity and a relationship with positive symptoms. Fourteen schizophrenic patients and 13 healthy comparison subjects viewed pictures during [15O] water positron emission tomography (PET). Both groups reported identical subjective experience of the aversive stimuli and both activated right insula (AV-NA). The schizophrenic group showed greater activation of the medial prefrontal cortex (MPFC) for the AV-NA comparison. Control subjects activated bilateral amygdaloid and orbitofrontal regions for NA relative to a blank condition (simple visual fixation, BL), whereas schizophrenic subjects only activated left orbitofrontal cortex. Activity in the left amygdala correlated with positive symptoms in the patients. Both groups activated visual cortex, and the schizophrenic subjects exhibited less modulation throughout visual cortex for NA-BL, as well as more focused deficits in the left fusiform and left mid-occipital gyrus for AV-NA, possibly related to decreased eye movements in the schizophrenic patients. Overall, the data are consistent with a general failure to process salient stimuli in schizophrenia, and the findings support the involvement of the amygdala in the positive symptoms of schizophrenia.

Extended Amygdala and Emotional Salience: A PET Activation Study of Positive and Negative Affect

Functional neuroimaging studies have implicated amygdaloid and basal forebrain regions, including sublenticular extended amygdala (SLEA), in the mediation of aversive emotional responses. However, it is not clear whether SLEA responds to ‘aversiveness’ or to general stimulus salience. We predicted that both pleasant and aversive stimuli would activate this region. Using [15O] water PET, we studied 10 healthy subjects while viewing pleasant, aversive, neutral, and blank images. Each subject underwent eight scans, which were processed and averaged with standard statistical methods. Both positive and negative stimuli activated regions in SLEA. Both positive and negative content activated the visual cortex, relative to neutral content. Aversive stimuli deactivated the left frontal pole, relative to positive and neutral stimuli. These findings demonstrate that both positive and negative emotional content evokes processing in the sublenticular/extended amygdala region, suggesting that this region is involved in general emotional processing, such as detection or attribution of salience.

Limbic Activation and Psychophysiologic Responses to Aversive Visual Stimuli: Interaction with Cognitive Task

We mapped regional brain activity and peripheral psychophysiologic responses, occurring in response to evocative emotional stimuli, and examined whether task instructions could modulate limbic activation. Ten subjects viewed pictures with neutral or aversive emotional content during simultaneous measurement of peripheral psychophysiology and brain activity with [15O]water positron emission tomography (PET). Cognitive task was manipulated by having the subjects rate the pictures or perform a recognition memory task. Aversive pictures, relative to neutral pictures, increased cerebral activity in bilateral amygdala, thalamic/hypothalamic area, midbrain, and left lateral prefrontal cortex, along with greater skin conductance responses (SCR). Voxel-by-voxel correlation coefficients between regional brain activity and SCR showed significant positive correlation peaks in the thalamus and right amygdala. Limbic activation was significantly greater during the rating condition compared to the recognition condition, suggesting that when task demands modify emotional responses, this modulation can occur at the level of limbic activity.

Biological predictors of suicidality in schizophrenia

The objective of this study was to determine whether polysomnographic rapid eye movement (REM) sleep abnormalities and cortisol response to the dexamethasone suppression test (DST) differentiate between schizophrenic patients with and without a history of suicidal behaviour. We assessed a sample of 96 schizophrenic in-patients at the end of a 2-week medication-free period with the DST, polysomnography, and an extensive clinical assessment battery. Patients exhibiting suicidal behaviour were significantly more likely to have increased total REM time and increased total REM activity. We found no significant relationship between suicidal behaviour and DST non-suppression. This study confirms a previous finding suggesting an association between REM sleep abnormalities and suicidal behaviour in schizophrenia. It is postulated that this observed association may be related to serotonergic dysfunction in schizophrenia.

Familial/sporadic schizophrenia: Differences in neuropsychological function

There is now substantial evidence that both genetic and environmental factors play a role in the etiology of schizophrenia; however, little is known about the relationships between these factors and known markers for schizophrenia. In this paper we apply the familial/sporadic subtyping method as a first step towards examining the contribution of familial (approximated to genetic in this study) and environmental factors to relevant neurobiological markers in schizophrenia. Specifically, we compare cerebral ventricular size and neuropsycho[ogical function in schizophrenic patients with and without a first-degree relative with schizophrenia. Family history was ascertained by interview with the patient and a family member and a review of the medical record in 48 schizophrenic inpatients diagnosed by SADS/RDC and DSM-III-R criteria. Seven patients had a first-degree relative with schizophrenia. Neuropsychological functions were measured on the Wechsler Adult Intelligence Scale-Revised (full scale IQ, verbal IQ, and performance IQ); Trail Making Test Part B; Reaction Time (choice); Wisconsin Card Sorting Test (WCST); and the Controlled Oral Word Association Test. IQ, Trails B, and WCST scores were standardized to acoount for differences in age, sex, and education levels. Ventricle-brain ratios (VBRs) were calculated from CT scans. Patients with positive (FHpos) and negative (FHneg) family histories did not differ on the severity of either positive or negative symptomatology. Our results showed that a negative family history was associated with increased VBR (means -FHpos: 0.06; FHneg: 0.09; p = 0.06); these findings are consistent with several other reports. Of the neuropsychological indicators, only scores on Trails B differed significantly in the FHpos and FHneg groups; positive family history was associated with worse functioning (FHpos: 62.7; FHneg: 84.1; Mann-Whitney U: p = 0.01). These data suggest that nonfamilial factors contribute to ventricular enlargement while familial factors contribute to frontal lobe deficits in schizophrenia. This might reflect the presence of ventricular enlargement and frontal lobe neuropsychological dysfunction on separate pathogenetic pathways in schizophrenia. The results support the utility of the familial/sporadic approach in studying the pathogenetic heterogeneity of schizophrenia.

Cognitive effects of typical and atypical antipsychotics in schizophrenia

The aim of the present study was to investigate the relationship between differential pharmacotherapy and cognitive functioning across an acute schizophrenic episode. We used a repeated measures design to assess neuropsychological functioning (attention, memory, executive function, motor speed) and clinical symptoms (positive symptoms, negative symptoms, general psychopathology from the SANS and BPRS) in a sample of 27 inpatients who met DSM-1II-R and SADS/RDC criteria for schizophrenia. Patients were assessed upon admission and were reassessed shortly before discharge (mean time between assessments = 17.7 days). The total sample was comprised of four subgroups based on pharmacotherapy status at the time of the two a s s e s s m e n t s ~ r o u p 1 : neuroleptic free to atypical neuroleptic (clozapine or risperidone); Group 2: neuroleptic free to typical neuroleptics; Group 3: typical neuroleptics to atypical neuroleptics; and Group 4: atypical neuroleptics to atypical neuroleptics. Significant improvement was observed across assessments for measures of verbal fluency (p = 0.004) and sustained attention (p = 0.005), which were related to time, but not to differences in pharmacotherapy status. Correlational analysis revealed that improvement in measures of memory storage and retrieval (Wechsler Memory Scale), as well as attentional flexibility (Trailmaking, Paced Auditory Serial Addition Test) were associated with clinical reduction in positive symptoms (range of r: 0.51-0.72). Improvement in general cognitive status (Mini Mental Status Examination) was associated with negative symptom reduction (r = 0.52). These findings imply that reduction in clinical symptoms, rather than type of pharmacotherapy, may predict neuropsychological improvement across an acute episode.