Projects

Background: Cross-sectional studies indicate that a substantial proportion of refugees have psychiatric disorders. However, longitudinal studies on the course of psychiatric symptoms and on influencing factors are scarce. The current study investigates the development of symptoms in an untreated refugee sample in Germany and seeks to identify potential predictors.
Methods: Over the course of one year, 57 refugees participated in monthly assisted self-reports on the phone assessing emotional distress. At the same time, semi-annual, semi-structured clinical interviews focusing on posttraumatic stress disorder (PTSD) and depression were conducted. The overall dropout rate for the year was 23% for the assisted self-reports and 33% for the clinical interviews.
Results: Symptoms did not systematically change over the course of the year. On the individual level, a reliable change in PTSD symptoms was observed in 13% who showed improvement and 24% who showed worsening symptoms. Figures for depression symptoms were 24% and 16% respectively. A higher number of traumatic experiences was related to a greater intensity of PTSD symptoms. In addition, postmigrational stressors were associated with a worsening of PTSD symptoms over the course of the year. Emotional distress was associated with current negative life events, unemployment, and frequent visits to physicians.
Conclusions: There is on average no improvement or worsening of symptoms over the period of one year. However, individual courses vary, and thus show the importance of risk factors. Accordingly, the identification of risk factors such as trauma load and postmigrational stressors can be useful to determine the need of further monitoring and to provide appropriate interventions when necessary.

Appetitive aggression is a sub-category of instrumental aggression, characterised by the primary intrinsic enjoyment of aggressive activity. Aggression is heritable, and serotonergic and monoaminergic neurotransmitter systems have been found to contribute to the underlying molecular mechanisms. The aim of this study was to investigate the role that genetic variants in the serotonin transporter (SLC6A4) and monoamine oxidase A (MAOA) genes play in the aetiology of appetitive aggression in South African Xhosa males (n = 290). SLC6A4 5-HTTLPR, rs25531, and STin2 variants, as well as MAOA-uVNTR were investigated for their association with levels of appetitive aggression using Poisson regression analysis. The STin2 VNTR12 allele was found to be associated with increased levels of appetitive aggression (p = 0.003), but with decreased levels of reactive aggression (p = 7 × 10^-5). This study is the first to investigate genetic underpinnings of appetitive aggression in a South African population, with preliminary evidence suggesting that SCL6A4 STin2 variants play a role in its aetiology, and may also be important in differentiating between appetitive and reactive aggression. Although the results require replication, they shed some preliminary light on the molecular dichotomy that may underlie the two forms of aggression.

The Good: when you fight to counter threat, your aggression is a reactive defense, and often morally justifiable. The Bad: when you loot and rob, hurt and kill, to obtain social status or material goods, that is an extrinsic reward. This is instrumental aggression. And The Ugly: The intrinsic enjoyment of violence. This ‘appetitive aggression’ describes a lust for violence, underlying first-person shooter gamers, hunting, and extreme acts of violence, such as murder and massacres. Although violence often results from a combination of these forms of aggression, the differentiation is necessary to understand their interplay, as they drive two interconnected cycles of violence: the reactive cycle, fueled by the motivation to overcome negative feelings, and the hedonically driven appetitive cycle.

Objective:
Past research revealed war trauma and posttraumatic stress disorder (PTSD) symptoms as potential predictors for domestic and community violence in crisis regions and among soldiers in different armed conflicts. The impact of family violence and other adversities experienced in childhood as well as of a combat-enhanced appeal for aggressive behavior (appetitive aggression) remains to be specified.
Method:
In the present study, the authors separately predicted violence against children, intimate partner violence and community violence in 381 Burundian soldiers returning from foreign deployment and living in a post- conflict region. Using path analysis, they aimed to disentangle the independent contributions and pathways of the following variables: Exposure to war trauma and childhood familial violence, PTSD and depression symptom severity, and appetitive aggression.
Results:
Childhood familial violence had an independent effect on all contexts of violence and was the only significant predictor for violence against the soldiers’ own children. Intimate partner violence was additionally predicted by depression symptom severity, while community violence was additionally predicted by PTSD symptom severity and appetitive aggression.
Conclusions:
Besides war-related mental ill-health and appetitive aggression, violent experiences during childhood development must not be overlooked as a factor fueling the cycle of violence in conflict regions.

Post-Traumatic Stress Disorder (PTSD) has been linked to deviations in lateralized frontal functional oscillatory activity. This is possibly because left and right DLPFC have differential roles in regulating both memory and stress response, which are both dysfunctional in PTSD. However, previous results are heterogeneous, and could be attributable to individual symptom clusters, traumatic or aggressive life events, early life stress, or the interaction of these factors. In a large sample of active combatants (N=401), we regressed these factors on frontal electroencephalography (EEG) asymmetry across 5 frequency bands (delta: 2-4Hz; theta: 4-8Hz; alpha: 8-12Hz; beta: 12-24Hz; gamma: 24-48Hz). Negative cognition and mood was associated with stronger relative left delta and theta band power. Traumatic life events showed stronger right alpha and beta band power. Traumatic life events in interaction with hyperarousal predicted stronger relative right left-right imbalance (theta, alpha, and beta bands), whereas childhood adversity, in interaction with negative cognition and mood, predicted stronger relative left left-right imbalance (delta, theta, alpha and beta bands). The contribution of lateralized DLPFC dysfunction to PTSD is thus dependent on the individual complexities of subsymptom clusters and life history, and future studies need to take these factors into account.

Stress during pregnancy may impact subsequent generations, which is demonstrated by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although the importance of the prenatal environment is well reported with regards to future physical and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR<0.05) associated with the grandmother's report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDR<0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.

Exposure to traumatic stressors and subsequent trauma-related mental changes may alter a person's risk-taking behavior. It is unclear whether this relationship depends on the specific types of traumatic experiences. Moreover, the association has never been tested in displaced individuals with substantial levels of traumatic experiences. The present study assessed risk-taking behavior in 56 displaced individuals by means of the balloon analogue risk task (BART). Exposure to traumatic events, symptoms of posttraumatic stress disorder and depression were assessed by means of semi-structured interviews. Using a novel statistical approach (stochastic gradient boosting machines), we analyzed predictors of risk-taking behavior. Exposure to organized violence was associated with less risk-taking, as indicated by fewer adjusted pumps in the BART, as was the reported experience of physical abuse and neglect, emotional abuse, and peer violence in childhood. However, civil traumatic stressors, as well as other events during childhood were associated with lower risk taking. This suggests that the association between global risk-taking behavior and exposure to traumatic stress depends on the particular type of the stressors that have been experienced.

Appetitive aggression is the attraction to violent behavior, which can peak in the experience of a combat high. In various war and conflict scenarios, members of armed groups have reported developing a desire to hunt and even kill humans. More recently, we reported that the phenomenon has also been observed in female ex-combatants with varying participation in warfare. Despite recent investigations on risk factors for appetitive aggression, sex-specific pathways in the development of appetitive aggression have not yet been delineated. This study investigated moderation effects of sex on previously identified risk factors for appetitive aggression by means of regression analyses in a sample of individuals with varying degrees of warfare participation (overall sample, n = 602). First examining a sample characterized by backgrounds heterogeneous in both sociodemographic data and war experiences, the analysis was then replicated in a subsample of fighters active during the civil war (combatant sample, n = 109). In both samples, regression analyses revealed significant moderation effects of sex. Childhood maltreatment and traumatic events had positive associations on the development of appetitive aggression for males but a negative (childhood maltreatment) or no (traumatic events) association for females. Perpetrated events were more strongly correlated with appetitive aggression for females than for males. This pattern was pronounced for the combatant sample. These results are in favor of sex-linked pathways. In both sexes, appetitive aggression may have evolved as a biologically prepared response to cruel environments but might develop along different trajectories. The current study highlights the need for addressing appetitive aggression in order to support peace-building processes and emphasizes sex specific starting-points.

Objective: In an observer-blinded intervention trial, we tested the reduction of posttraumatic stress symptoms, aggressive attitude, and behavior in young males living in a context of ongoing community and gang violence by means of (a) forensic offender rehabilitation narrative exposure therapy (FORNET), and (b) the cognitive-behavioral intervention "Thinking for a Change" (TFAC). A waiting list served as the control condition. Method: A total of 39 young men were included in the data analysis: 15 completed FORNET, 11 underwent cognitive-behavioral therapy (CBT), and 13 were on a waiting list for later treatment. The primary efficacy endpoints were the PTSD Symptom Scale-Interview (PSS-I) severity score, the Appetitive Aggression Scale (AAS) score, and the number of perpetrated violent event types 8 months (on average) after treatment. Results: Only in the sample receiving FORNET were posttraumatic stress disorder (PTSD) scores significantly reduced at the first follow-up (Cohen's d = -0.97) and significantly different from those of the control group (Cohen's d = -1.03). The changes in scores for appetitive aggression and perpetrated events were not significant for any of the treatment conditions. Conclusions: The study shows that trauma-focused treatment can reduce the psychological symptoms of posttraumatic stress even for individuals living under unsafe conditions in low-income urban communities. However, achieving changes in violent behavior within a context of ongoing violence may require more than the treatment of trauma-related suffering, confrontation with one's offenses, or cognitive-behavioral interventions.

Violence exposure poses a risk for posttraumatic stress disorder (PTSD) and appetitive aggression. Does acknowledgment of violent experiences by one’s social environment also affect these adverse consequences of violence? We investigated relations between number of traumatic event types, number of violent offenses, PTSD symptoms, appetitive aggression, and social acknowledgment. A total of 290 participants were recruited through a Cape Town rehabilitation center for offenders. Using path analysis, we demonstrate higher societal disapproval to be associated with more intense PTSD symptoms and greater appetitive aggression. However, past experiences of recognition were also related to more intense PTSD symptoms. Violence exposure was positively associated with PTSD symptoms and appetitive aggression, and a higher number of violent offenses was related to greater appetitive aggression. Results indicate that besides violence exposure, social acknowledgment may play a significant role in the severity of PTSD and appetitive aggression. Intervention programs should not neglect targeting social structures.

Background: In violent communities, social rejection as a person with victim–offender attributes is associated with more intense symptoms of posttraumatic stress disorder (PTSD) and a higher propensity towards violence, i.e. appetitive aggression. Successful community reintegration encompassing adequate social acknowledgment of individuals with both a history of violence exposure and perpetration may be necessary to enhance the treatment effects of interventions addressing PTSD and aggression.
Objective: In this study, the effects of treatment and post-treatment traumatic events, violent offenses, and social acknowledgment (with sub-dimensions of general disapproval, family disapproval, and recognition as a person with both a history of violence exposure and commission) on changes in PTSD symptom severity and appetitive aggression from baseline to 8-month follow-up were investigated.
Method: Data were collected from 54 males recruited through a Cape Town offender reintegration programme for an intervention study targeting trauma and aggression (n = 28 treatment; n = 26 wait-list). Changes in PTSD symptom severity after treatment were assessed with the PTSD Symptom Scale-Interview, changes in appetitive aggression with the Appetitive Aggression Scale (AAS), post-treatment traumatic events with an adapted version of the Child’s Exposure to Violence Checklist, offenses with an adapted checklist from the AAS, and social acknowledgment with an adapted form of the Social Acknowledgment Questionnaire. Results: Path analyses revealed negative relationships between ongoing societal disapproval and changes in PTSD symptom severity and appetitive aggression at 8-months, controlling for age. All other variables were non-significant, except for treatment, which was associated with PTSD symptom reduction. Conclusions: As a complementary strategy to effective psychotherapeutic treatment, increased social acknowledgment may contribute significantly to the alleviation of PTSD symptoms and appetitive aggression. Psychological interventions should, therefore, not neglect the impact of societal factors on treatment effects.

Background

In persistently unsafe environments, the cumulative exposure to violence predicts not only the development of posttraumatic stress disorder (PTSD), but also of increased aggression and violent outbursts. Substance use disorders interact with these developments, as drug consumption may blunt symptoms and also reduce the threshold for violent acts. Investigating the interplay between these variables and the possible cumulative effect of drug abuse on the attraction to cruelty is a crucial step in understanding the cycle of violence and developing intervention programs that address this cycle in violence-troubled communities such as low-income urban areas in South Africa.

Methods

Young males at risk (N = 290) were recruited through a reintegration center for offenders in Cape Town. We assessed types of traumatic events experienced, PTSD symptom severity, appetitive aggression, committed offenses and patterns of drug abuse prior to the perpetration of violence.

Results

Path-analyses confirmed a positive relationship between exposure to traumatic events and PTSD symptom severity, appetitive aggression, the number of committed offenses and drug abuse prior to violence. PTSD symptoms were positively associated with the propensity toward aggression. Furthermore, more severe drug abuse was related to higher attraction to violence and more committed offenses.

Conclusions

We conclude that like exposure to violence, drug abuse may play a key role in the attraction to aggression and criminal acts. Measures of violence prevention and psychotherapeutic interventions for trauma-related suffering may not be effective without enduring drug abuse rehabilitation.

Belastende Kindheitserfahrungen erhöhen die Wahrscheinlichkeit für psychopathologische Entwicklungen. Misshandelte Kinder weisen ein mehrfaches Risiko auf an Depressionen zu erkranken. Der Krankheitsverlauf beginnt früher, ist schwerer und die Behandlungserfolge sind verringert. Personen, die besonders zurückweisungsempfindlich sind, berichten außerdem mehr belastende Kindheitserfahrungen. In der vorliegenden Studie wird in einer allgemeinpsychiatrischen Klinik mit stationärer und tagesklinischer Behandlung der Zusammenhang zwischen belastender Kindheit und Verlauf der Depression sowie Zurückweisungsempfindlichkeit quantifiziert. Bei 48 Patienten mit einer Diagnose der Depression (F31, F32, F33) wurde zu Behandlungsbeginn und -ende mit einem Selbsteinschätzungs- (BDI) und einem Fremdeinschätzungsmaß (HAM-D) die Schwere depressiver Symptomatik beurteilt. Während des Aufenthalts wurden die Patienten mit der «Skala belastende Kindheitserfahrungen» (KERF-I, Kurzversion) zu belastenden Kindheitserlebnissen interviewt und füllten einen Fragebogen zu Zurückweisungsempfindlichkeit (RSQ) aus. Die Hypothesen wurden mit Korrelationsanalysen getestet. Belastende Kindheitserfahrungen waren mit der BDI-basierten Selbsteinschätzung der Depressivität positiv assoziiert, aber nicht mit dem HAM-D Rating. Patienten mit rezidivierender Depression berichteten doppelt so viele belastende Erfahrungen in ihrer Kindheit als Patienten mit einer einzelnen depressiven Episode. Dreifach höhere Belastungswerte zeigten sich bei Patienten in stationärer Behandlung gegenüber solchen in tagesklinischer Behandlung. Belastende Kindheitserfahrungen waren mit einer erhöhten Zurückweisungsempfindlichkeit assoziiert und diese mit einem geringeren Therapieerfolg. Die Zusammenhänge von belastenden Kindheitserfahrungen mit depressiver Symptomatik und Zurückweisungsempfindlichkeit geben Hinweise auf die Bildung negativer kognitiver Schemata. Die negative Korrelation von Therapieerfolg und Zurückweisungsempfindlichkeit bietet eine Erklärung für den ungünstigeren Verlauf einer depressiven Erkrankung bei Patienten mit vielen belastenden Kindheitserfahrungen.

Former combatants have experienced many traumatic events and violence in their past. Symptoms of posttraumatic stress disorder (PTSD) are prevalent among them, but at the same time, many combatants do not suffer from PTSD. Appetitive aggression—the perception of violent acts as appealing and exciting—was found to reduce the risk of developing PTSD symptoms in several studies with combatants of different countries. However, this protective influence waned when traumatization of combatants got too severe. The aim of the present study was to replicate previous findings in a sample of Burundian ex-combatants. The relationship between appetitive aggression and PTSD symptom severity was investigated, and a negative correlation between these variables was expected. On the basis of previous studies, we expected to find this relationship only after excluding the most traumatized participants. Semistructured interviews were conducted with 392 Burundian ex-combatants to assess traumatic event types, self-committed violent acts, PTSD symptom severity (PTSD Symptom Scale Interview) and appetitive aggression (Appetitive Aggression Scale). Appetitive aggression was not correlated with PTSD symptoms severity in the total sample. After the most severely traumatized participants were excluded, appetitive aggression was negatively related to PTSD symptom severity. The findings of the present study confirmed previous findings on the relationship between appetitive aggression and PTSD. Appetitive aggression was shown to lower PTSD symptom severity but is no ultimate protection against PTSD.

Appetitive aggression refers to positive feelings being associated with the perpetration of violent behavior and has been shown to provide resilience against the development of PTSD in combatants returning from the battlefield. Until this point, appetitive aggression has been primarily researched in males. This study investigates appetitive aggression in females. Female and male combatants and civilians from Burundi were assessed for levels of appetitive aggression. In contrast to non-combatants, no sex difference in appetitive aggression could be detected for combatants. Furthermore, each of the female and male combatant groups displayed substantially higher levels of appetitive aggression than each of the male and female civilian control groups. This study demonstrates that in violent contexts, such as armed conflict, in which individuals perpetrate numerous aggressive acts against others, the likelihood for an experience of appetitive aggression increases- regardless of whether the individuals are male or female.

Background: Experiencing abuse during childhood affects the psychological well-being of individuals throughout their lives and may even influence their offspring by enhancing the likelihood of an intergenerational transmission of violence. Understanding the effects of childhood maltreatment on child-rearing practices and intimate partner violence might be of particular importance to overcome the consequences of violent conflicts in African societies.

Objective: Using Burundi as an example, we aimed to explore the associations between childhood maltreatment, intimate partner violence, perceived partner intimidation, gender and the probability of violently acting out against one's own children or romantic partner.

Methods: Amongst a sample of 141 men and 141 women in the capital of Burundi, we identified those who had biological children and those who lived or had lived in relationships. Using culturally appropriate instruments, we enquired about their exposure to childhood maltreatment and partner violence as well as their inclinations to act out violently.

Results: We found that childhood maltreatment and perceived partner intimidation were strong predictors for the perpetration of violence against children. Moreover, we found that women were more likely to use violence against children if they experienced partner violence and less likely to resort to violence if they felt intimidated. Men were more likely to perpetrate violence against their partner. Childhood maltreatment was again a strong predictor. The more women experienced partner violence, the more they fought back.

Conclusions: Childhood maltreatment is a strong predictor for domestic violence and has to be addressed to interrupt the cycle of violence in post-conflict countries.

Research has identified appetitive aggression, i.e., the perception of committed, violent acts as appealing, exciting and fascinating, as a common phenomenon within populations living in precarious and violent circumstances. Investigating demobilized soldiers in the Democratic Republic of Congo (DRC) demonstrated that violent offending is associated with appetitive aggression and not necessarily with symptoms of posttraumatic stress. In the present study, we sought to replicate these results in an independent and larger sample of demobilized soldiers from Burundi. As with the Congolese ex-combatants, random forest regression revealed that the number of lifetime perpetrated violent acts is the most important predictor of appetitive aggression and the number of lifetime experienced traumatic events is the main predictor for posttraumatic stress. Perpetrated violent acts with salient cues of hunting (pursuing the victim, the sight of blood, etc.) were most predictive for perceiving violent cues appealingly after demobilization. Moreover, the association of violent acts and appetitive aggression as well as traumatic events and posttraumatic stress remains strong even years after demobilization. Patterns of traumatic events and perpetrated acts as predictors for posttraumatic stress and appetitive aggression seem to be robust among different samples of ex-combatants who fought in civil wars. Psychotherapeutic interventions that address these complementary facets of combat-related disorders-namely, posttraumatic stress and appetitive aggression-are indispensable for a successful reintegration of those who fought in armed conflicts and to achieve a successful transition to peace.

Former members of armed groups in eastern DR Congo had typically witnessed, experienced, and perpetrated extreme forms of violence. Enhanced trauma-related symptoms had been shown in prior research. But also lashing out in self-defense is a familiar response to threat defined as reactive aggression. Another potential response is appetitive aggression, in which the perpetration of excessive violence is perceived as pleasurable (combat high). What roles do these forms of aggressive behavior play in modern warfare and how are they related to posttraumatic stress symptoms? To answer the question, we sought to determine predictors for appetitive aggressive and trauma-related mental illness, and investigated the frequency of psychopathological symptoms for high- and low-intensity conflict demobilization settings. To this end, we interviewed 213 former members of (para)military groups in the eastern Democratic Republic of Congo in regard to their combat exposure, posttraumatic stress, appetitive aggression, depression, suicidality, and drug dependence. Random forest regression embedded in a conditional inference framework revealed that perpetrated violent acts are not necessarily stressful. In fact, the experience of violent acts that typically implicated salient cues of hunting (e.g., blood, suffering of the victim, etc.) had the strongest association with an appetite for aggression. Furthermore, the number of lifetime perpetrated violent acts was the most important predictor of appetitive aggression. However, the number of perpetrated violent acts did not significantly affect the posttraumatic stress. Greater intensity of conflict was associated with more severe posttraumatic stress symptoms and depression. Psychotherapeutic interventions that address appetitive aggression in addition to trauma-related mental illness, including drug dependence, therefore seem indispensible for a successful reintegration of those who fought in the current civil wars.

This study investigated the impact of violent experiences during childhood, posttraumatic stress disorder (PTSD) and appetitive aggression on everyday violent behavior in Burundian females with varying participation in war. Moreover, group differences in trauma-related and aggression variables were expected. Appetitive aggression describes the perception of violence perpetration as fascinating and appealing and is a common phenomenon in former combatants. Semi-structured interviews were conducted with 158 females, either former combatants, supporters of armed forces or civilians during the civil war in Burundi. The PTSD Symptom Scale Interview was used to assess PTSD symptom severity, the Appetitive Aggression Scale to measure appetitive aggression and the Domestic and Community Violence Checklist to assess both childhood maltreatment and recent aggressive behavior. Former combatants had experienced more traumatic events, perpetrated more violence and reported higher levels of appetitive aggression than supporters and civilians. They also suffered more severely from PTSD symptoms than civilians but not than supporters. The groups did not differ regarding childhood maltreatment. Both appetitive aggression and childhood violence predicted ongoing aggressive behavior, whereas the latter outperformed PTSD symptom severity. These findings support current research showing that adverse childhood experiences and a positive attitude toward aggression serve as the basis for aggressive behavior and promote an ongoing cycle of violence in post-conflict regions. Female members of armed groups are in need of demobilization procedures including trauma-related care and interventions addressing appetitive aggression.

The objectives of this study were to investigate rates of posttraumatic stress disorder (PTSD) and levels of appetitive aggression and potential risk factors for appetitive aggression in a sample of 200 Rwandan genocide perpetrators. Five percent of the perpetrators presented with PTSD, and high levels of appetitive aggression were common. High levels of appetitive aggression were associated with male gender, a high number of past committed offenses, and low levels of positive and elevated levels of negative religious coping. Considering the substantial extent of appetitive aggression, the reintegration of these individuals into the community should consider the inclusion of programs that restrain appetitive aggression and restore psychological functioning to facilitate a peaceful coexistence.

Aggressive behavior is thought to divide into two motivational elements: The first being a self defensively motivated aggression against threat and a second, hedonically motivated ‘appetitive’ aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N=50) presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG). Results show differences in left frontal regions in delta (2-5 Hz) and alpha band (8-12 Hz) for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry.