Patrizia Thoma

Response inhibition and cognitive flexibility in schizophrenia with and without comorbid substance use disorder.

Addiction is a frequent comorbid disorder in schizophrenia related to dopaminergic dysfunction in fronto-subcortical circuits. These brain networks are relevant for both (executive) cognition and the neuropathology of schizophrenia. The aim of the present study was to elucidate whether response inhibition and cognitive flexibility - executive abilities relevant for achieving and maintaining abstinence - are differentially impaired in schizophrenia patients with or without comorbid substance use disorder. Patients suffering from major depression or alcoholism as well as healthy controls served as comparison groups. The ability to inhibit predominant response tendencies during response conflict and to efficiently shift the focus of attention between different task requirements was assessed by verbal and non-verbal cognitive tasks. Contrary to expectation, non-addicted schizophrenia patients showed the most pronounced executive function impairments relative to the control groups, affecting both response suppression and cognitive flexibility. Dual diagnosis patients did not differ significantly from non-addicted schizophrenia patients or from the alcoholic group, but were impaired at cognitive flexibility relative to the depression subgroup and healthy controls. Whether the relative preservation of response inhibition and cognitive flexibility in the dual disorder patients is due to high premorbid functioning, beneficial self-medication effects or compensatory brain activation remains to be elucidated. The relatively intact executive abilities in young, addicted schizophrenia patients might represent a beneficial resource for treatment strategies.

Neurocognitive mechanisms of figurative language processing : Evidence from clinical dysfunctions

The interpretation of proverbs has a long tradition in the assessment of abstract thinking, particularly in schizophrenia. Although the usefulness of proverb interpretation as a diagnostic tool has been questioned over the years, the comprehension of non-literal language nevertheless plays an important role in social interactions. Thus, researchers remain interested in the neurocognitive mechanisms mediating comprehension and use of figurative language. The present paper summarizes and evaluates the evidence from behavioral, lesion and imaging studies including data for compromised figurative language processing derived from clinical populations. One main focus is on studies of figurative language comprehension in schizophrenia. Several theoretical explanations proposed to account for the difficulties schizophrenia patients experience when confronted with figurative language will be addressed. An integration of the evidence from different areas of research is attempted and directions for future investigation are outlined.

Empathy and social problem solving in alcohol dependence, mood disorders and selected personality disorders

Altered empathic responding in social interactions in concert with a reduced capacity to come up with effective solutions for interpersonal problems have been discussed as relevant factors contributing to the development and maintenance of psychiatric disorders. The aim of the current work was to review and evaluate 30 years of empirical evidence of impaired empathy and social problem solving skills in alcohol dependence, mood disorders and selected personality disorders (borderline, narcissistic, antisocial personality disorders/psychopathy), which have until now received considerably less attention than schizophrenia or autism in this realm. Overall, there is tentative evidence for dissociations of cognitive (e.g. borderline personality disorder) vs. emotional (e.g. depression, narcissism, psychopathy) empathy dysfunction in some of these disorders. However, inconsistencies in the definition of relevant concepts and their measurement, scarce neuroimaging data and rare consideration of comorbidities limit the interpretation of findings. Similarly, although impaired social problem solving appears to accompany all of these disorders, the concept has not been well integrated with empathy or other cognitive dysfunctions as yet.

Cognitive and affective empathy in depression linked to executive control

Depression has been linked to executive dysfunction and emotion recognition impairments, associated with abnormalities in fronto-temporal and subcortical brain regions. Little is known about changes of different empathy subcomponents during depression, with potential impairments being related to the interpersonal difficulties of depressed patients. Twenty patients treated for an episode of unipolar depression and 20 matched healthy controls were assessed. Measures of dispositional and behavioural empathy components were administered along with tests of cognitive flexibility, response inhibition and working memory. Relative to controls, depressed patients showed higher self-reported dispositional empathy scores, mainly driven by increased personal distress scores. Patients and controls did not differ significantly in terms of behavioural cognitive empathy, empathic concern and personal affective involvement or in their executive function performance. In the patients, cognitive flexibility and response inhibition accuracy were associated with behavioural empathy. While an increased disposition towards feeling personal distress in response to other peoples suffering seems to be in generally related to depressive symptoms, behavioural empathy might depend on the functional integrity of executive control during an episode of clinical depression. Impairments in this regard could contribute to the interpersonal difficulties depressed patients are frequently faced with which might have important implications for treatment.

The Cerebellum Is Involved in Reward-based Reversal Learning

The cerebellum has recently been discussed in terms of a possible involvement in reward-based associative learning. To clarify the cerebellar contribution, eight patients with focal vascular lesions of the cerebellum and a group of 24 healthy subjects matched for age and IQ were compared on a range of different probabilistic outcome-based associative learning tasks, assessing acquisition, reversal, cognitive transfer, and generalization as well as the effect of reward magnitude. Cerebellar patients showed intact acquisition of stimulus contingencies, while reward-based reversal learning was significantly impaired. In addition, the patients showed slower acquisition of new stimulus contingencies in a second reward-based learning task, which might reflect reduced carry-over effects. Reward magnitude affected learning only during initial acquisition, with better learning on trials with high rewards in patients and control subjects. Overall, the findings suggest that the cerebellum is implicated in reversal learning as a dissociable component of reward-based learning.

Comorbid substance use disorder in schizophrenia: A selective overview of neurobiological and cognitive underpinnings

Although individuals with schizophrenia show a lifetime prevalence of 50% for suffering from a comorbid substance use disorder, substance abuse usually represents an exclusion criterion for studies on schizophrenia. This implies that surprisingly little is known about a large group of patients who are particularly difficult to treat. The aim of the present work is to provide a brief and non‐exhaustive overview of the current knowledgebase about neurobiological and cognitive underpinnings for dual diagnosis schizophrenia patients. Studies published within the last 20 years were considered using computerized search engines. The focus was on nicotine, caffeine, alcohol, cannabis and cocaine being among the most common substances of abuse. All drugs of abuse target dopaminergic, glutamatergic and GABAergic transmission which are also involved in the pathophysiology of schizophrenia. Current literature suggests that neurocognitive function might beless disrupted in substance‐abusing compared to non‐abusing schizophrenia patients, but in particular the neuroimaging database on this topic is sparse. Detrimental effects on brain structure and function were shown for patients for whom alcohol is the main substance of abuse. It is as yet unclear whether this finding might be an artifact of age differences of patient subgroups with different substance abuse patterns. More research is warranted on the specific neurocognitive underpinnings of schizophrenia patients abusing distinct psychoactive substances. Treatment programs might either benefit from preserved cognitive function as a resource or specifically target cognitive impairment in different subgroups of addicted schizophrenia patients.

Proverb Interpretation Changes in Aging.

Recent investigations have emphasized the involvement of fronto-subcortical networks to proverb comprehension. Although the prefrontal cortex is thought to be affected by normal aging, relatively little work has been carried out to investigate potential effects of aging on proverb comprehension. In the present investigation participants in three age groups were assessed on a proverb comprehension task and a range of executive function tasks. The older group showed impairment in selecting correct interpretations from alternatives. They also showed executive function deficits, as reflected by reduced working memory and deficient set shifting and inhibition abilities. The findings of the present investigation showed proverb comprehension deficits in normal aging which appeared to be related to reduced executive skills.

Mental state decoding and mental state reasoning in recently detoxified alcohol-dependent individuals

Impaired social cognition has been associated with interpersonal problems and with the development of and relapse into alcohol abuse. In the present study, self-reported trait empathy, decoding of complex mental states and cognitive and affective mental state reasoning were assessed in alcohol-dependent participants, and the association with executive function and psychopathological characteristics was investigated. Twenty recently detoxified alcohol-dependent patients and 20 matched healthy controls were assessed with an abbreviated German version of the interpersonal reactivity index, the revised reading the mind in the eyes test, the faux pas story test, the trail making test and the letter-number-sequencing test. Patients were impaired relative to controls with regard to mental state decoding on the eyes test and showed reduced faux pas detection and impaired mental state reasoning reflected by lower faux pas understanding and faux pas empathy scores. There were no group differences regarding self-reported trait empathy. Performance on the sociocognitive measures was related to executive functioning and the severity of depressive symptoms. Although self-report measures might not always reliably detect impairments of social cognition, behavioural measures suggest pronounced impairments of mental state decoding and mental state reasoning in association with alcohol dependence. Findings ought to be incorporated into current treatment strategies.

Subcortical contributions to multitasking and response inhibition.

The involvement of the prefrontal cortex in executive control has been well established. It is, however, as yet unclear whether the basal ganglia and the cerebellum as components of frontostriatal/frontocerebellar networks also contribute to the executive domains multitasking and response inhibition. To investigate this issue, groups of patients with selective vascular lesions of the basal ganglia (n=13) or the cerebellum (n=14) were compared with matched healthy control groups. Several paradigms assessing the ability to process concurrent visual and auditory input and to simultaneously perform verbal and manual responses as well as the inhibition of habitual or newly acquired response tendencies were administered. Basal ganglia patients showed marked response slowing during coordination of sensory input from different modalities and high error rates during the inhibition of overlearned responses. There was no clear evidence of a cerebellar involvement in multitasking or response suppression. Taken together, the findings provided evidence for a striatal involvement in both multitasking and response inhibition, emphasizing the functional implication of subcortical components in frontostriatal circuits.

Face and body perception in schizophrenia: a configural processing deficit?

Face and body perception rely on common processing mechanisms and activate similar but not identical brain networks. Patients with schizophrenia show impaired face perception, and the present study addressed for the first time body perception in this group. Seventeen patients diagnosed with schizophrenia or schizoaffective disorder were compared to 17 healthy controls on standardized tests assessing basic face perception skills (identity discrimination, memory for faces, recognition of facial affect). A matching-to-sample task including emotional and neutral faces, bodies and cars either in an upright or in an inverted position was administered to assess potential category-specific performance deficits and impairments of configural processing. Relative to healthy controls, schizophrenia patients showed poorer performance on the tasks assessing face perception skills. In the matching-to-sample task, they also responded more slowly and less accurately than controls, regardless of the stimulus category. Accuracy analysis showed significant inversion effects for faces and bodies across groups, reflecting configural processing mechanisms; however reaction time analysis indicated evidence of reduced inversion effects regardless of category in schizophrenia patients. The magnitude of the inversion effects was not related to clinical symptoms. Overall, the data point towards reduced configural processing, not only for faces but also for bodies and cars in individuals with schizophrenia.