Christian Stephan-Otto

Abnormal functioning of the semantic network in schizophrenia patients with thought disorganization. An exemplar production task.

Numerous studies have indicated that thought disorganization in schizophrenia is associated with an enhanced semantic priming effect. This suggests abnormal functioning of the semantic network in these patients, with disinhibited spreading of semantic activation. We investigated whether thought disorganization is also associated with atypical responses in the production of semantic category exemplars. An exemplar production task was administered to 43 patients with schizophrenia and 24 healthy controls. The names of 16 semantic categories were provided, and the participants were requested to produce an exemplar for each category. The typicality of the response was rated according to norms. Higher ratings of thought disorganization were associated with the production of more atypical exemplars. In addition, the patients with high thought disorganization scores were significantly more atypical in their responses than were the healthy controls. In contrast, the patients with low thought disorganization scores were equivalent to the healthy controls. Higher ratings of affective flattening were associated with the production of less atypical exemplars. The results corroborate, within a different paradigm than semantic priming, the theory that thought disorganization is associated with faster and more distant connections within the semantic network. This effect is counteracted by affective flattening.

Decreased processing speed might account for working memory span deficit in schizophrenia, and might mediate the associations between working memory span and clinical symptoms.

OBJECTIVE Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms. METHOD Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed. RESULTS The working memory span was significantly impaired in patients (F(1,90)=4.6, P<0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89)=0.03, P=0.86, and F(1,89)=0.03, P=0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r=-0.52, P<0.0001) and thought disorganisation (r=-0.34, P<0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β=-0.12, P=0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β=-0.10, P=0.26). CONCLUSIONS Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.

Functional similarity of facial emotion processing between people with a first episode of psychosis and healthy subjects

BACKGROUND Neurofunctional and behavioral abnormalities in facial emotion processing (FEmoP) have been consistently found in schizophrenia patients, but studies assessing brain functioning in early phases are scarce and the variety of experimental paradigms in current literature make comparisons difficult. The present work focuses on assessing FEmoP in people experiencing a psychotic episode for the first time with different experimental paradigm approaches. METHODS Twenty-two patients with a first psychotic episode (FPe) (13 males) took part in a functional magnetic resonance imaging study (1.5T) examining neural responses to explicit and implicit processing of fearful and happy facial expressions presented at two different intensities: 50% and 100%. Their brain activation was compared to that of 31 healthy subjects (15 males). RESULTS Control subjects show differential patterns of brain activation regarding the task demands (implicit or explicit processing), the emotional content (happy or fear) and the intensities of the emotion (50% or 100%); such differences are not found in participants with a first psychotic episode (FPe). No interaction or group effects are seen between control and FPe participants with any of the emotional tasks assessed, although FPe subjects show worse behavioral performance. CONCLUSIONS No brain areas recruited for FEmoP emerge as significantly different between people with a FPe and healthy subjects, independently on the demands of the task, the emotion processed, or the intensity of the emotion; but FPe participants show a limited recruitment of differential brain regions that could be associated with poor emotional processing in the short term. Our results outline the need of investigating the underlying processes that lead FPe participants to worse FEmoP performance.

Visual Imagery and False Memory for Pictures: A Functional Magnetic Resonance Imaging Study in Healthy Participants.

Background Visual mental imagery might be critical in the ability to discriminate imagined from perceived pictures. Our aim was to investigate the neural bases of this specific type of reality-monitoring process in individuals with high visual imagery abilities. Methods A reality-monitoring task was administered to twenty-six healthy participants using functional magnetic resonance imaging. During the encoding phase, 45 words designating common items, and 45 pictures of other common items, were presented in random order. During the recall phase, participants were required to remember whether a picture of the item had been presented, or only a word. Two subgroups of participants with a propensity for high vs. low visual imagery were contrasted. Results Activation of the amygdala, left inferior occipital gyrus, insula, and precuneus were observed when high visual imagers encoded words later remembered as pictures. At the recall phase, these same participants activated the middle frontal gyrus and inferior and superior parietal lobes when erroneously remembering pictures. Conclusions The formation of visual mental images might activate visual brain areas as well as structures involved in emotional processing. High visual imagers demonstrate increased activation of a fronto-parietal source-monitoring network that enables distinction between imagined and perceived pictures.

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms

BACKGROUND Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. METHODS We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age=36.9; 11 females) and 20 schizophrenia patients (age=39.9; 8 females) in an fMRI study. RESULTS In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster)<0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster)<0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster)<0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. CONCLUSIONS Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas.

Effects of caffeine intake and smoking on neurocognition in schizophrenia.

Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.

Global brain asymmetry is increased in schizophrenia and related to avolition

Schizophrenia may be the result of a failure of the normal lateralization process of the brain. However, whole‐brain asymmetry has not been assessed up to date. Here, we propose a novel measure of global brain asymmetry based on the Dice coefficient to quantify similarity between brain hemispheres.

Impaired Self-Monitoring of Inner Speech in Schizophrenia Patients with Verbal Hallucinations and in Non-clinical Individuals Prone to Hallucinations

Background: Previous research has shown that various memory errors reflecting failure in the self-monitoring of speech were associated with auditory/verbal hallucinations in schizophrenia patients and with proneness to hallucinations in non-clinical individuals. Method: We administered to 57 schizophrenia patients and 60 healthy participants a verbal memory task involving free recall and recognition of lists of words with different structures (high-frequency, low-frequency, and semantically organisable words). Extra-list intrusions in free recall were tallied, and the response bias reflecting tendency to make false recognitions of non-presented words was computed for each list. Results: In the male patient subsample, extra-list intrusions were positively associated with verbal hallucinations and inversely associated with negative symptoms. In the healthy participants the extra-list intrusions were positively associated with proneness to hallucinations. A liberal response bias in the recognition of the high-frequency words was associated with verbal hallucinations in male patients and with proneness to hallucinations in healthy men. Meanwhile, a conservative response bias for these high-frequency words was associated with negative symptoms in male patients and with social anhedonia in healthy men. Conclusion: Misattribution of inner speech to an external source, reflected by false recollection of familiar material, seems to underlie both clinical and non-clinical hallucinations. Further, both clinical and non-clinical negative symptoms may exert on verbal memory errors an effect opposite to that of hallucinations.

Three-Dimensional Map of Neonatal Arterial Ischemic Stroke Distribution From Early Multimodal Brain Imaging

Background and Purpose— Although neonatal arterial ischemic stroke (NAIS) location has considerable impact on long-term outcome, a map showing spatial distribution of NAIS is lacking. Our aim was to generate this distribution map, based on early magnetic resonance imaging data. Methods— Lesions from 34 consecutive neonates with NAIS from a single center were segmented using multimodal magnetic resonance imaging (median age at acquisition =5 days). Lesion masks for all subjects were registered onto a standard neonatal brain and then overlaid to generate a 3D map of NAIS distribution. Results— The region posterior to the central sulcus is the most frequently affected in neonates, with 24 of the 34 neonates (71%) showing lesions in this region in at least one hemisphere. Moreover, NAIS frequency is markedly higher in the left hemisphere. Conclusions— This is the first report of an NAIS distribution map. Regions posterior to the central sulcus present increased vulnerability. Our findings suggest that motor areas are not as frequently affected as has been previously reported. By contrast, we find high NAIS vulnerability in functional areas related to language. The distribution of ischemic strokes in neonates seems to be different from that seen in adults.

Association of auditory-verbal and visual hallucinations with impaired and improved recognition of colored pictures.

OBJECTIVE A number of cognitive underpinnings of auditory hallucinations have been established in schizophrenia patients, but few have, as yet, been uncovered for visual hallucinations. In previous research, we unexpectedly observed that auditory hallucinations were associated with poor recognition of color, but not black-and-white (b/w), pictures. In this study, we attempted to replicate and explain this finding. Potential associations with visual hallucinations were explored. METHOD B/w and color pictures were presented to 50 schizophrenia patients and 45 healthy individuals under 2 conditions of visual context presentation corresponding to 2 levels of visual encoding complexity. Then, participants had to recognize the target pictures among distractors. RESULTS Auditory-verbal hallucinations were inversely associated with the recognition of the color pictures presented under the most effortful encoding condition. This association was fully mediated by working-memory span. Visual hallucinations were associated with improved recognition of the color pictures presented under the less effortful condition. Patients suffering from visual hallucinations were not impaired, relative to the healthy participants, in the recognition of these pictures. CONCLUSION Decreased working-memory span in patients with auditory-verbal hallucinations might impede the effortful encoding of stimuli. Visual hallucinations might be associated with facilitation in the visual encoding of natural scenes, or with enhanced color perception abilities.