A cerebellar approach to aggression

Abstract

The aim of this thesis was to examine the contribution of the cerebellum to motivational processes and reward- and punishment-based learning processes associated with aggression. Chapter 2 reviewed evidence from lesion, structural and functional neuroimaging and brain stimulation studies in support of a role of the cerebellum in aggression. The evidence points towards a differential contribution of the medial and lateral cerebellum to aggression. In particular, the medial cerebellum is involved in emotion-driven, fast responding during imminent threat and provocation and mediates impulsive aggression. In contrast, the posterolateral cerebellum is involved in slower, top-down cognitive control processes which support premeditated and instrumental forms of aggression. Chapters 3 and 4 tested the cerebellar lateralization hypothesis of motivational direction in approach-related aggressive (chapter 3) and avoidance-related (chapter 4) behavior. In chapter 3, a baseline and during-task state anger-dependent increase in aggressive behavior was found during left cathodal-right anodal cerebellar as compared to sham tDCS. Furthermore, aggression was positively correlated with heart rate during active tDCS, while an inverse association was observed during sham tDCS. Subsequently, the reversed bipolar cerebellar tDCS montage (i.e., left anodal-right cathodal) was applied in chapter 4 to study its effect on reversal learning during threat of shock. Higher levels of shock anxiety were associated with increased reversal learning rate after the first reversal in the active compared to sham tDCS condition. Additionally, higher scores on trait impulsivity were associated with reduced reversal learning rate after the second reversal in the active compared to sham tDCS condition. The results from chapters 3 and 4 support the cerebellar lateralization model of motivational direction, which states that left-to-right dominant cerebellar activity is associated with avoidance (flight) motivation, whereas right-to-left dominant cerebellar activity is associated with approach (fight) motivation. Moreover, the results demonstrate affective context-relevant state- and trait-dependent effects of cerebellar tDCS. In addition, this thesis examined the contributions of the cerebellum to reward- and punishment-based learning processes to get insights into the role of motivated learning and mental flexibility in aggressive behavior. The activation likelihood estimation meta-analysis of functional MRI studies in chapter 5 revealed distinct patterns of cerebellar activity associated with reward anticipation and reward outcome processing in healthy adults. More specifically, reward anticipation was associated with activity in the bilateral anterior lobe, bilateral lobule VI, left Crus I and the posterior vermis, while reward outcome was associated with activity in the declive and left lobule VI. In chapter 6, cTBS was applied to the cerebellum of healthy adult volunteers to investigate the direct contribution of the cerebellum to reward- and punishment-based reversal learning. Medial posterior cerebellar cTBS reduced learning rate after the first reversal and diminished the implementation of the optimal strategy after learning the second reversal as compared to right posterolateral cerebellar and right occipital lobe cTBS. Taken together, the findings of this thesis support the involvement of the cerebellum in motivational and reward- and punishment-based learning processes associated with aggression. In the remainder of this chapter, these findings as well as potential clinical implications will be discussed.