Christian Kärgel

Attenuated prefrontal activation during decision-making under uncertainty in schizophrenia: A multi-center fMRI study

Decisions are called decisions under uncertainty when either prior information is incomplete or the outcomes of the decision are unclear. Alterations in these processes related to decisions under uncertainty have been linked to delusions. In patients with schizophrenia, the underlying neural networks have only rarely been studied. We aimed to disentangle the neural correlates of decision-making and relate them to neuropsychological and psychopathological parameters in a large sample of patients with schizophrenia and healthy subjects. Fifty-seven patients and fifty-seven healthy volunteers from six centers had to either indicate via button-press from which of two bottles red or blue balls were drawn (decision-making under uncertainty condition), or indicate whether eight red balls had been presented (baseline condition) while BOLD signal was measured with fMRI. Patients based their decisions on less conclusive evidence and had decreased activations in the underlying neural network, comprising of medial and lateral frontal as well as parietal areas, as compared to healthy subjects. While current psychopathology was not correlated with brain activation, positive symptoms led to longer decision latencies in patients. These results suggest that decision-making under uncertainty in schizophrenia is affected by a complex interplay of aberrant neural activation. Furthermore, reduced neuropsychological functioning in patients was related to impaired decision-making and task performance was modulated by distinct positive symptoms.

Mismatch Negativity Latency and Cognitive Function in Schizophrenia

Background The Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to neuropsychological (working memory and verbal domains) and psychosocial measures. While MMN amplitude is thought to be correlated with deficits of early sensory processing, the functional significance of MMN latency remains unclear so far. The present study focused on the investigation of MMN in relation to neuropsychological function in schizophrenia. Method Forty schizophrenia patients and 16 healthy controls underwent a passive oddball paradigm (2400 binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2 kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery. Patients were assessed with regard to clinical symptoms. Results Compared to healthy controls schizophrenia patients showed diminished MMN amplitude and shorter MMN latency to both deviants as well as an impaired neuropsychological test performance. Severity of positive symptoms was related to decreased MMN amplitude to duration deviants. Furthermore, enhanced verbal memory performance was associated with prolonged MMN latency to frequency deviants in patients. Conclusion The present study corroborates previous results of a diminished MMN amplitude and its association with positive symptoms in schizophrenia patients. Both, the findings of a shorter latency to duration and frequency deviants and the relationship of the latter with verbal memory in patients, emphasize the relevance of the temporal aspect of early auditory discrimination processing in schizophrenia.

Diminished functional connectivity on the road to child sexual abuse in pedophilia.

BACKGROUND Pedophilia is a disorder recognized for its impairment to the individual and for the harm it may cause to others. However, the neurobiology of pedophilia and a possible propensity to sexually abuse children are not well understood. In this study, we thus aimed at providing new insights in how functional integration of brain regions may relate to pedophilia or child sexual abuse (CSA). METHOD By using functional magnetic resonance imaging (fMRI) technique, we compared functional connectivity at rest (RSFC) between pedophiles who engaged (P+CSA; N = 12) or did not engage (P-CSA; N = 14) in CSA and healthy controls (HCs; N = 14) within two networks: (i) the default mode network and (ii) the limbic network that has been linked to pedophilia before. RESULTS Pedophiles who engaged in CSA show diminished RSFC in both networks compared with HC and P-CSA. Most importantly, they showed diminished RSFC between the left amygdala and orbitofrontal as well as anterior prefrontal regions. Though significant age differences between groups could not be avoided, correlation control analysis did not provide evidence for the assumption that the RSFC effects were related to age differences. CONCLUSION We found significantly diminished RSFC in brain networks critically involved in widespread motivational and socio-emotional processes. These results extend existing models of the functional neuroanatomy of pedophilia and CSA as altered RSFC between these regions were related to CSA rather than pedophilia and thus may account for an increased propensity to engage in CSA in people suffering from pedophilia.

Evidence for superior neurobiological and behavioral inhibitory control abilities in non‐offending as compared to offending pedophiles

Neurobehavioral models of pedophilia and child sexual offending suggest a pattern of temporal and in particular prefrontal disturbances leading to inappropriate behavioral control and subsequently an increased propensity to sexually offend against children. However, clear empirical evidence for such mechanisms is still missing. Using a go/nogo paradigm in combination with functional magnetic resonance imaging (fMRI) we compared behavioral performance and neural response patterns among three groups of men matched for age and IQ: pedophiles with (N = 40) and without (N = 37) a history of hands‐on sexual offences against children as well as healthy non‐offending controls (N = 40). As compared to offending pedophiles, non‐offending pedophiles exhibited superior inhibitory control as reflected by significantly lower rate of commission errors. Group‐by‐condition interaction analysis also revealed inhibition‐related activation in the left posterior cingulate and the left superior frontal cortex that distinguished between offending and non‐offending pedophiles, while no significant differences were found between pedophiles and healthy controls. Both areas showing distinct activation pattern among pedophiles play a critical role in linking neural networks that relate to effective cognitive functioning. Data therefore suggest that heightened inhibition‐related recruitment of these areas as well as decreased amount of commission errors is related to better inhibitory control in pedophiles who successfully avoid committing hands‐on sexual offences against children. Hum Brain Mapp 38:1092–1104, 2017.

Electrophysiological mismatch response recorded in awake pigeons from the avian functional equivalent of the primary auditory cortex.

The neural response to occasional variations in acoustic stimuli in a regular sequence of sounds generates an N-methyl-D-aspartate receptor-modulated event-related potential in primates and rodents in the primary auditory cortex known as mismatch negativity (MMN). The current study investigated MMN in pigeons (Columba livia L) through intracranial recordings from Field L of the caudomedial nidopallium, the avian functional equivalent of the mammalian primary auditory cortex. Auditory evoked field potentials were recorded from awake birds using a low-frequency (800 Hz) and high-frequency (1400 Hz) deviant auditory oddball procedure with deviant-as-standard (flip-flop design) and multiple-standard control conditions. An MMN-like field potential was recorded and blocked with systemic 5 mg/kg ketamine administration. Our results are similar to human and rodent findings of an MMN-like event-related potential in birds suggestive of similar auditory sensory memory mechanisms in birds and mammals that are homologue from a common ancestor 300 million years ago or resulted from convergent evolution.

Neural correlates of moral judgment in pedophilia

Abstract Pedophilia is a sexual preference that is often associated with child sex offending (CSO). Sexual urges towards prepubescent children and specifically acting upon those urges are universally regarded as immoral. However, up until now, it is completely unknown whether moral processing of sexual offenses is altered in pedophiles. A total of 31 pedophilic men and 19 healthy controls were assessed by using functional magnetic resonance imaging (fMRI) in combination with a moral judgment paradigm consisting of 36 scenarios describing different types of offenses. Scenarios depicting sexual offenses against children compared to those depicting adults were associated with higher pattern of activation in the left temporo-parietal-junction (TPJ) and left posterior insular cortex, the posterior cingulate gyrus as well as the precuneus in controls relative to pedophiles, and vice versa. Moreover, brain activation in these areas were positively associated with ratings of moral reprehensibility and negatively associated with decision durations, but only in controls. Brain activation, found in key areas related to the broad network of moral judgment, theory of mind and (socio-)moral disgust - point to different moral processing of sexual offenses in pedophilia in general. The lack of associations between brain activation and behavioral responses in pedophiles further suggest a biased response pattern or dissected implicit valuation processes.

Executive Functioning in Pedophilia and Child Sexual Offending

OBJECTIVES Pedophilia (P) is a psychiatric disease associated with sexual attraction toward children and often accompanied by child sexual offending (CSO). Consequently, it is important to address the understanding of executive dysfunctions that may increase the probability of CSO. Moreover, this research field has been lacking to disentangle executive deficits associated with pedophilia (as a deviant sexual preference) from those associated with CSO (as a deviant sexual behavior). METHODS The German multi-sided research network NeMUP offers the opportunity to overcome these limitations. By applying the Cambridge Automated Neuropsychological Test Battery in four carefully matched groups of men: (1) pedophiles with (N=45) and (2) without (N=45) a history of sexual offending against children; (3) child molesters without pedophilia (N=19), and (4) non-offending controls (N=49), we were able to analyze executive functioning in pedophilia and CSO independently. RESULTS Both CSO groups as compared to both non-CSO groups exhibited worsened response inhibition ability. However, only non-pedophilic offenders showed additionally disabled strategy use ability. Regarding set-shifting abilities, the P+CSO group showed the best performance. We also found that performances were affected by age: only in pedophiles, response inhibition worsened with age, while age-related deficits in set-shifting abilities were restricted to non-pedophilic participants. The latter also differentiated between both sexual preference groups. CONCLUSIONS Our results are the first to demonstrate that executive dysfunctions are related to offense status rather than pedophilic preference. Furthermore, there was evidence for differentiating age and performance correlations between pedophiles and non-pedophiles, which warrants further investigation. (JINS, 2017, 23, 460-470).

The effect of deviance predictability on mismatch negativity in schizophrenia patients

Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients.

The effect of cognitive training on evoked potentials in schizophrenia

Electrophysiological indices are sensitive to cognitive dysfunction in schizophrenia but have rarely been used to assess benefits of cognitive remediation. Our aim was to evaluate the effect of specific cognitive training approaches on event-related potentials. Forty-six patients with schizophrenia underwent either auditory (AUD) or visuo-spatial (VIS) cognitive training or treatment-as-usual (TAU). Cognitive training was computer-assisted and administered for 10 sessions within two weeks. Event-related potentials during an active odd-ball paradigm together with clinical and neuropsychological variables were assessed before and after training and again at a two-month follow-up. Compared to the TAU group both the AUD and VIS training groups showed decreased P2 latency following training. At follow-up, the P2-latency reduction was stable in the VIS group but the AUD group experienced a relapse. Training resulted in improved digit-span backward among neuropsychological variables. Increased P2 amplitude was related to more positive symptoms and lower social-occupational functioning and longer P2 latency was associated with greater severity of stereotyped thinking. The more general visuo-spatial training appears to have a longer-lasting effect on P2 latency than the specific auditory training. Alternatively, there may be specific auditory discrimination deficits in schizophrenia requiring more extensive training for a stable change.

Approach and Avoidance Tendencies Toward Picture Stimuli of (Pre-)Pubescent Children and Adults: An Investigation in Pedophilic and Nonpedophilic Samples:

The presence of pedophilic sexual interests is considered of high importance for predicting recidivism among individuals who have committed sexual offenses. However, objective and valid assessment methods that are robust against confounding issues such as cognitive capacity and manipulation are sparse. We applied the Approach–Avoidance Task (AAT) for detecting sexual interests in 38 pedophilic men (18 primarily attracted to boys) and 27 male nonpedophilic (11 gay) participants. The AAT relies on automatic approach and avoidance tendencies, independent of cognitive abilities such as memory capacity and intelligence. Approach–avoidance tendencies toward stimuli depicting seminude prepubescent boys and girls as well as men and women are reported. The results were consistent with previous research on the utility of the AAT: Except for pedophiles attracted to girls, the mean AAT scores (approach minus avoidance reaction time for each stimulus category) were positive only for stimuli of the preferred category. A multivariate binary logistic regression approach revealed 80% overall accuracy in differentiating pedophilic from nonpedophilic participants.