Experimental Design

To investigate if severe criminal psychopaths are able to gain control of their frontal brain activity and if psychopathic traits such as impulsivity, aggression and excessive behavioral approach will improve after the learned regulation of frontal brain excitation thresholds, we conducted a pre/post-multilevel-cross-validated intensive brain regulation intervention study with a clinically referred sample (Proof-of-Principle). Only an experimental group of criminal participants was trained, aiming to investigate the possibility of brain changes in highly psychopathic offenders after learned SCP-self-control (Justifications of the design in Supplement “(B) Design of clinical-effect studies in psychopathic offenders”-section). SCP-differentiation neurofeedback data of comparable, healthy controls and various patient groups exist for comparison purposes30,40,45,46,47,48,49 (Supplement “(A) SCP-Neurofeedback Research”-section).

Participants

We recruited patients with a long history of criminal records related to serious violent and/or sexual offences (like murder, repeated sexual assault and violent robbery), serving long term sentences in two forensic psychiatric institutions with high security regulations in Germany. Based on the Psychopathy-Checklist-Revised (PCL-R1) and on the current clinical status, the final sample consisted of 14 male, adult (mean age: 43.14 ± 11.52 years, all right handed) psychopathic patients with a mean PCL-R score of 30.14 (range: 26–34) (Supplement “(C) Study Subject Recruiting”-section). Patients with an IQ below 80 (on CFT20-R58), neurological and medical illnesses or head injuries, as well as patients with major Axis I diagnosis of psychosis, obsessive-compulsive disorder, tics or Tourette- syndrome were excluded. None of the patients received antipsychotic or sedative medication. In agreement with the forensic institutions, offenders received financial compensation for the extensive SCP-training intervention, independent of their performance. Written informed consent was obtained of all participants before being involved in the study. This study was approved by the Ethics Committee of the Medical Faculty of the University of Tübingen according to the Declaration of Helsinki.

Experimental Procedure and Material

a) Slow Cortical Potential Neurofeedback Training

Slow Cortical Potentials were recorded at FCz (Figure 4b) and fed back to the patients' monitor using graphical objects matched to preferences of the participants (e.g. fish, moon etc.). Each trial started with a triangle, pointing upwards for a required negative SCP-shift and downwards for a required positive SCP-shift. Participants were instructed to move the object, developing their individual strategy. The instruction emphasized, that muscular (i.e. tension-relaxation) or respiratory strategies disturb self-regulation performance. Successful changes in cortical activity were rewarded with the symbol of a sun after each trial, as the only performance-dependent reinforcement.

Figure 4 Study Design. (a). Upper row : Procedure and Timing with Pre-Assessment, SCP-Training Phase 1 (12 days), Training break (13 days; Patients were instructed to exercise regulation skills on their own, using a small card showing their preferred training object), SCP-Training Phase 2 (13 days) and Post-Assessment. Middle row : Example of one training session (~60 minutes per day) consisting of three blocks with different conditions: 1.Feedback-> 2. Transfer-> 3. Feedback. Lower row: Example of the time course of an SCP training trial with a 2 sec baseline and the following 8 sec regulation phase is depicted. The upper curve indicates a negative SCP shift, lower curve a positive SCP shift.(b). Location of the EEG feedback site: FCz is depicted (gray). Full size image

All participants underwent 25 SCP-training sessions (each about 60 minutes/day) during a three-month intervention period. The SCP-training consisted of two phases of 13 and 12 training days with a 13 days break. During the break, participants were asked to exercise regulation skills with their individual training strategies using a small reminder card, showing their preferred training object (e.g. fish, moon etc.) to consolidate and transfer successful self-regulation performance.

Each training session consisted of 120 trials, divided into 3 training blocks with different conditions: the first and the last training block were feedback blocks in which the object (e.g. a fish) moved from left to right over the screen to provide feedback according to the SCP activity. The middle training block was designed as a transfer block in which the object (e.g. the fish) did not appear on the subjects' monitor - only a blue screen was presented during the SCP regulation task without any feedback of brain activity to the person (except the symbol of the sun after successful regulation trials). One single training trial comprised a 2 second baseline followed by an 8 second active regulation phase. During the Inter-Trial-Interval (ITI; varying between 1 and 2 sec, randomized) an empty blue screen or -after successful regulation trials, a reinforcement screen (with a symbol of a sun)- was presented. Required negativity (50% in the first; 80% in the second training phase) and required positivity (50% in the first; 20% in the second training phase) were presented in random order in accordance with established neurofeedback training protocols in ADHD. Every SCP-training session started with an eye movement calibration task, which was used for an online eye movement artefact correction during the training to control und minimize influences caused by eye movements59. An overview of the study design, an example of one session (including feedback and transfer blocks) and one trial are given in Figure 4a, Figure 4b depicts the location of the EEG feedback site: FCz.

b) Self-Report Measures

All questionnaires were handed to the participants before and after the SCP-training (Figure 4). Aggression was assessed using the German questionnaire for the assessment of aggressiveness factors (FAF54) and the Buss-Perry-Aggression Questionnaire (BPAQ52). The Behavior-Inhibition/Behavior-Activation System Questionnaire (BIS/BAS53) served as an index for behavioral approach (BAS), sensitive to reward and associated with aggression, anger and impulsivity3,4,53 and behavioral inhibition (BIS), sensitive to punishment and related to anxiety53.

c) Flanker Task

To investigate impulsivity, attention, error processing as well as behavioral inhibition, a modified letter version of the Eriksen Flanker Task60 was applied before and after SCP-training (Figure 4). In the letter flanker task, participants had to respond to the center letter of a 5-letter string with a right hand button press for the target ‘S’ and a left hand button press for the target ‘H’ (button-letter arrangement was counterbalanced), while they should not press any button if ‘X’ was the center letter (‘non-target trials’). The letter strings of the ‘target trials’ were either congruent (HHHHH or SSSSS) or incongruent (SSHSS or HHSHH), as well as the ‘non-target trials’ (congruent: XXXXX, incongruent: SSXSS or HHXHH), with the incongruent condition characterized by a higher degree of difficulty (stimulus congruency effect). After a red fixation cross on white background, the black letter strings appeared on the screen for 150 ms followed by an inter-trial interval of 1000 ms. In total 400 trials including 20% non-target trials (both with the same amount of congruent and incongruent trials) were presented.

To investigate cortical activity related to error-processing, two Event-Related Potentials (ERPs) were analyzed: the Error Related Negativity (ERN), reflecting early stages in error monitoring without conscious awareness of the errors and the following Error Positivity (Pe), associated with later stages of error processing with conscious awareness of the errors61. On the behavioral level, the number of correct and incorrect responses, omissions and commissions, as well as reaction times were recorded. Written instructions were given and test comprehension was evaluated with exercise trials before starting the computerized task.

EEG-Recording and Data Processing

EEG measurements were collected using a 22-channel Theraprax Q-EEG-System (NeuroConn GmbH, Illmenau, Germany). During SCP-training recordings the electrode FCz was used, while Fz, FCz, Cz and Pz were recorded during the Eriksen Flanker Task. The left mastoid was used as reference and the right mastoid as ground. Electrooculography was measured by placing electrodes above and below the left eye for blinks and vertical eye movements and at the outer canthi for horizontal eye movements. Electrode impedances were kept below 3kOhm throughout the study. The signals were recorded with a sampling rate of 128 Hz and with a 40 Hz low pass filter. EEG artifacts were detected automatically during the SCP-training recordings by the Theraprax System with a movement artifact correction or the trial was cancelled and repeated. Data from the eye movement calibration task before each training session was used for online artefact correction during the training to control und minimize influences caused by eye movements43. All EEG data were further processed using Brain Vision Analyzer Professional 2.01 (BrainProducts GmbH, Gilching, Germany). The signal was 50 Hz notch filtered and EOG artifacts were additionally corrected offline, based on Gratton et al.62.

From artifact-free SCP-training recordings, data between 0.1–2 Hz was used and baseline corrected, relative to -2000 ms pre-regulation phase. For each participant, the SCP-recordings were separately averaged for the two conditions (feedback and transfer) and tasks (required positivity and negativity) for each session. Only the last four seconds of each regulation trial were used for SCP-amplitudes to exclude influences of early ERPs on the SCP data.

Regarding the physiological Flanker-Task analysis, a 1–30 Hz filter was used for all midline positions. Artifact-free EEG recordings for non-target- and target-trials were time-locked to response onset and averaged separately for correct and incorrect responses for each participant relative to a -500 ms pre-response baseline. ERN was defined as the most negative peak in the 20–150 ms period following response onset at fronto-central sites. Pe was split into two components: the early Pe was defined as the most positive peak between 150-260 ms, while the late Pe was calculated for 261–350 ms post-response at Cz. ERN and Pe peak amplitudes were considered based on the correct-, the incorrect- (error) and the difference-waveform (errorwave minus correctwave) of each participant pre and post SCP-training.

Statistical Analysis

At first, the mean SCP-differentiation (mean µV-amplitude difference between required positivity and negativity) was calculated for each participant and for each of the 25 sessions, separately for feedback- and for transfer-condition. In order to examine the group performance of the SCP-training, paired sample t-tests were used to compare the average SCP-amplitude of the first six and the last six training sessions, reflecting the total regulation performance (across all trials) and separately for feedback- and transfer-condition. For a detailed examination of the learning course of regulation skills over time, linear regression analyses were performed using the average SCP-differentiation as independent and time (25 sessions) as the dependent variable. For analyses regarding relationships between individual training performance and changes in self-report measures (post-pre), an individual learning-indicator, the regression coefficient (non-standardized ß-value of the linear regression for each participant, separately for both conditions) was used.

Pre-post training comparisons regarding changes in questionnaire scores were performed using paired sample t-tests. In order to test for an association between these changes in time (post-pre) and the training performance, Pearson correlations were performed.

For the analysis of the Flanker Task, paired sample t-tests were used to detect changes in behavioral responses (number of correct/erroneous responses for both conditions and reaction times) as well as to detect changes in peak values for ERN and Pe (amplitude and latency based on the correct-, erroneous- and difference wave).

Although no violation of the normal distribution was found in the data, non-parametric analysis were additionally performed, but yielded the same results and were therefore omitted in the present text. Bonferroni correction was applied for multiple comparisons (which resulted in a corrected α of 0.025 for BIS/BAS- and a corrected α of 0.01 for FAF-questionnaire pre/post analyses). Since there were a priori directed hypotheses, one tailed p-values were used for all statistical analyses.