Bilateral Amygdala Radio-Frequency Ablation for Refractory Aggressive Behavior Alters Local Cortical Thickness to a Pattern Found in Non-refractory Patients.

Flavia Venetucci Gouveia,Rosa M C B Morais,Jürgen Germann,M Mallar Chakravarty,Erich T Fonoff,Helena Brentani,Raquel C R Martinez,Gabriel A Devenyi

doi:10.3389/fnhum.2021.653631

Abstract

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

Highlights

MATERIALS AND METHODSAggressive behavior is a multifactorial behavioral syndrome that includes physical aggression and/or verbal aggression and can be directed at oneself, to others, and to objects (Corrigan et al, 1993; Yudofsky et al, 2012)
After surgery the refractory group showed a marked reduction in aggressive behavior, showing reduction in total Overt Aggression Scale (OAS) score (88% average) and in all subscales: verbal aggression (66% average), physical aggression against objects (91% average), physical aggression against oneself or himself (91% average), and physical aggression against other people (91% average; see Table 1 for individual improvement rate)
This study has investigated changes of cortical thickness and a number of different aggressive behaviors following treatment in patients with refractory aggressive behavior compared to non-refractory patients

Summary

MATERIALS AND METHODS

Aggressive behavior is a multifactorial behavioral syndrome that includes physical aggression and/or verbal aggression and can be directed at oneself (self-injury behavior), to others, and to objects (Corrigan et al, 1993; Yudofsky et al, 2012). Previous studies have shown that the bilateral ablation of the amygdala in patients with a wide range of psychiatric disorders associated with severe and/or refractory aggressive behavior can successfully reduce the frequency and/or severity of aggressive behavior and improve patients’ quality of life (Kiloh et al, 1974; Balasubramaniam and Kanaka, 1975; Gouveia et al, 2019, 2021). The marked reduction in aggressive behavior observed in these severe cases following the ablation of the amygdala will affect the neurocircuitry of aggressive behavior, and this circuit-wide restoration of functional equilibrium should be associated with measurable plastic changes (Siever, 2008) To address this hypothesis, in this study we investigated changes in cortical thickness in patients presenting refractory aggressive behavior who were treated with bilateral amygdala radio-frequency ablation for symptom alleviation as compared to patients presenting non-refractory aggressive behavior. All analyses were corrected for multiple comparisons using False Discovery Rate (FDR) at the pFDRcor < 0.05 threshold

RESULTS

DISCUSSION

ETHICS STATEMENT