Alexander Rapp

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Laterality in metaphor processing: Lack of evidence from functional magnetic resonance imaging for the right hemisphere theory

We investigated processing of metaphoric sentences using event-related functional magnetic resonance imaging (fMRI). Seventeen healthy subjects (6 female, 11 male) read 60 novel short German sentence pairs with either metaphoric or literal meaning and performed two different tasks: judging the metaphoric content and judging whether the sentence has a positive or negative connotation. Laterality indices for 8 regions of interest were calculated: Inferior frontal gyrus (opercular part and triangular part), superior, middle, and inferior temporal gyrus, precuneus, temporal pole, and hippocampus. A left lateralised network was activated with no significant differences in laterality between the two tasks. The lowest degree of laterality was found in the temporal pole. Other factors than metaphoricity per se might trigger right hemisphere recruitment. Results are discussed in the context of lesion and hemifield studies.

Neural correlates of metaphor processing in schizophrenia

OBJECTIVE A main feature of schizophrenic thought and language disturbance is concretism, the inability to understand the figurative meaning of proverbs and metaphors. Although this is routinely tested during clinical interview, its neural basis is unknown. METHOD We investigated processing of metaphoric sentences with functional magnetic resonance imaging (fMRI) in 12 patients with schizophrenia and 12 control subjects. Stimuli consisted of 60 novel short sentences with either metaphoric or literal meaning presented visually, intersparsed by a low level baseline (grey background). Subjects read these sentences silently and judged by button press whether they had a positive or negative connotation. RESULTS Reading metaphors in contrast to literal sentences revealed signal changes in the left inferior frontal gyrus in the control subjects (BA 45/47) and an area 3 cm dorsal to that in the patients (BA 45). Only activation in this area was negatively correlated with the severity of concretism rated with the PANSS. Comparison between groups for the contrast metaphors vs. low level baseline revealed stronger signal changes in the control group in the right superior/middle temporal gyrus (BA 39) and the left inferior frontal gyrus (BA 45) in the patients. CONCLUSIONS The results in the control subjects are in line with studies showing an involvement of the left inferior frontal and right lateral temporal cortex during context processing. Failure to recruit these areas in the patients may underlie schizophrenic concretism.

Where in the brain is nonliteral language? A coordinate-based meta-analysis of functional magnetic resonance imaging studies.

An increasing number of studies have investigated non-literal language, including metaphors, idioms, metonymy, or irony, with functional magnetic resonance imaging (fMRI). However, key questions regarding its neuroanatomy remain controversial. In this work, we used coordinate-based activation-likelihood estimations to merge available fMRI data on non-literal language. A literature search identified 38 fMRI studies on non-literal language (24 metaphor studies, 14 non-salient stimuli studies, 7 idiom studies, 8 irony studies, and 1 metonymy study). Twenty-eight studies with direct comparisons of non-literal and literal studies were included in the main meta-analysis. Sub-analyses for metaphors, idioms, irony, salient metaphors, and non-salient metaphors as well as studies on sentence level were conducted. Studies reported 409 activation foci, of which 129 (32%) were in the right hemisphere. These meta-analyses indicate that a predominantly left lateralised network, including the left and right inferior frontal gyrus; the left, middle, and superior temporal gyrus; and medial prefrontal, superior frontal, cerebellar, parahippocampal, precentral, and inferior parietal regions, is important for non-literal expressions.

Mismatch responses to randomized gradient switching noise as reflected by fMRI and whole-head magnetoencephalography

The central auditory system of the human brain uses a variety of mechanisms to analyze auditory scenes, among others, preattentive detection of sudden changes in the sound environment. Electroencephalography (EEG) and magnetoencephalography (MEG) provide a measure to monitor neuronal cortical currents. The mismatch negativity (MMN) or field (MMNm) reflect preattentive activation in response to deviants within a sequence of homogenous auditory stimuli. Functional magnetic resonance imaging (fMRI) allows for a higher spatial resolution as compared to the extracranial electrophysiological techniques. The image encoding gradients of echo planar imaging (EPI) sequences, however, elicit an interfering background noise. To circumvent this shortcoming, the present study applied multi‐echo EPI mimicking an auditory oddball design. The gradient trains (SOA = 800 msec, 94.5 dB SPL, stimulus duration = 152 msec) comprised amplitude (−9 dB) and duration (76 msec) deviants in a randomized sequence. Moreover, the scanner noise was recorded and applied in a whole‐head MEG device to validate the properties of this specific material. Robust fMRI activation patterns emerged in response to the deviant gradient switching. Changes in amplitude activated the entire auditory cortex, whereas the duration deviants elicited right‐lateralized signal increase in secondary areas. The recorded scanner noise evoked reliably right‐lateralized mismatch MEG responses. Source localization was in accordance with activation of secondary auditory cortex. The presented paradigm provides a robust and feasible tool to study the functional anatomy of early cognitive auditory processing in clinical populations such as schizophrenia. Hum. Brain Mapping 16:190–195, 2002.

Cognition and Brain Function in Schizotypy: A Selective Review

Schizotypy refers to a set of personality traits thought to reflect the subclinical expression of the signs and symptoms of schizophrenia. Here, we review the cognitive and brain functional profile associated with high questionnaire scores in schizotypy. We discuss empirical evidence from the domains of perception, attention, memory, imagery and representation, language, and motor control. Perceptual deficits occur early and across various modalities. While the neural mechanisms underlying visual impairments may be linked to magnocellular dysfunction, further effects may be seen downstream in higher cognitive functions. Cognitive deficits are observed in inhibitory control, selective and sustained attention, incidental learning, and memory. In concordance with the cognitive nature of many of the aberrations of schizotypy, higher levels of schizotypy are associated with enhanced vividness and better performance on tasks of mental rotation. Language deficits seem most pronounced in higher-level processes. Finally, higher levels of schizotypy are associated with reduced performance on oculomotor tasks, resembling the impairments seen in schizophrenia. Some of these deficits are accompanied by reduced brain activation, akin to the pattern of hypoactivations in schizophrenia spectrum individuals. We conclude that schizotypy is a construct with apparent phenomenological overlap with schizophrenia and stable interindividual differences that covary with performance on a wide range of perceptual, cognitive, and motor tasks known to be impaired in schizophrenia. The importance of these findings lies not only in providing a fine-grained neurocognitive characterization of a personality constellation known to be associated with real-life impairments, but also in generating hypotheses concerning the aetiology of schizophrenia.

Humor and smiling Cortical regions selective for cognitive, affective, and volitional components

Background: The interrelationships among humor, smiling, and grinning have fascinated philosophers for millennia and neurologists for over a century. A functional dissociation between emotional facial expressions and those under voluntary control was suggested decades ago. Recent functional imaging studies, however, have been somewhat at odds with older studies with respect to the role of the right frontal cortex in the perception of humor. Methods: Blood oxygen level–dependent (BOLD) activity was measured in 13 subjects during the presentation of “funny” vs “nonfunny” versions of essentially the same cartoons and compared with BOLD activity associated with “merely grinning” at similar nonfunny cartoons via fMRI. Results: Humor perception was correlated with BOLD activity in the left temporo-occipitoparietal junction and left prefrontal cortex and humor-associated smiling (recorded with an MR-compatible video camera) with bilateral activity in the basal temporal lobes. Unexpectedly, both conditions were also accompanied by a decrease in BOLD activity in the right orbitofrontal cortex. Voluntary “grinning” in the absence of humorous stimuli was accompanied by bilateral activity in the facial motor regions. Conclusions: These results confirm the clinically derived hypothesis of separate cortical regions responsible for the production of emotionally driven vs voluntary facial expressions. The right orbitofrontal decrease reconciles inconsistencies between clinical and functional imaging findings and may reflect a disinhibition of facial emotional expression.

Neural Correlates of Irony Comprehension: The Role of Schizotypal Personality Traits.

To detect that a conversational turn is intended to be ironic is a difficult challenge in everyday language comprehension. Most authors suggested a theory of mind deficit is crucial for irony comprehension deficits in psychiatric disorders like schizophrenia; however, the underlying pathophysiology and neurobiology are unknown and recent research highlights the possible role of language comprehension abnormalities. Fifteen female right-handed subjects completed personality testing as well as functional magnetic resonance imaging (fMRI) and neuropsychology. Subjects were recruited from the general population. No subject had a lifetime history of relevant psychiatric disorder; however, subjects differed in their score on the German version of the schizotypal personality questionnaire (SPQ). During fMRI scans, the subjects silently read 44 short text vignettes that ended in either an ironic or a literal statement. Imaging was performed using a 3 T Siemens scanner. The influence of schizotypy on brain activation was investigated by using an SPM5 regression analysis with the SPQ total score and the SPQ cognitive-perceptual score as regressors. Reading ironic in contrast to literal sentences activated a bilateral network including left medial prefrontal and left inferior parietal gyri. During reading of ironic sentences, brain activation in the middle temporal gyrus of both hemispheres showed a significant negative association with the SPQ total score and the SPQ cognitive-perceptual score. Significant positive correlation with the SPQ total score was present in the left inferior frontal gyrus. We conclude schizotypal personality traits are associated with a dysfunctional lateral temporal language rather than a theory of mind network.

The precuneus and the insula in self-attributional processes

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people’s tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

Is impaired set-shifting a feature of ''pure'' anorexia nervosa? Investigating the role of depression in set-shifting ability in anorexia nervosa and unipolar depression

Impaired set-shifting has been reported in patients with anorexia nervosa (AN) and in patients with affective disorders, including major depression. Due to the prevalent comorbidity of major depression in AN, this study aimed to examine the role of depression in set-shifting ability. Fifteen patients with AN without a current comorbid depression, 20 patients with unipolar depression (UD) and 35 healthy control participants were assessed using the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and a Parametric Go/No-Go Test (PGNG). Set-shifting ability was intact in patients with AN without a comorbid depression. However, patients with UD performed significantly poorer in all three tasks compared to AN patients and in the TMT compared to healthy control participants. In both patient groups, set-shifting ability was moderately negatively correlated with severity of depressive symptoms, but was unrelated to BMI and severity of eating disorder symptoms in AN patients. Our results suggest a pivotal role of comorbidity for neuropsychological functioning in AN. Impairments of set-shifting ability in AN patients may have been overrated and may partly be due to comorbid depressive disorders in investigated patients.