Flavia Venetucci Gouveia1,2, Jürgen Germann3, Rosa de Morais4, Erich Talamoni Fonoff5, Clement Hamani2,5,6, Eduardo Joaquim Alho5, Helena Brentani7,8, Ana Paula Martins4, Gabriel Devenyi3, Raihaan Patel3, Christopher Steele3, Robert Gramer9, Mallar Chakravarty3, Raquel Chacon Ruiz Martinez1. 1. Laboratory of Neuromodulation, Teaching and Research Institute, Hospital Sirio-Libanes, Sao Paulo, Brazil. 2. Sunnybrook Research Institute, Toronto, Canada. 3. CIC, Douglas Mental Health University Institute, McGill University, Montreal, Canada. 4. PROTEA, Department of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil. 5. Department of Neurology, Division of Functional Neurosurgery, Institute of Psychiatry, Medical School, University of Sao Paulo, Sao Paulo, Brazil. 6. Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. 7. Department of Psychiatry, Medical School, University of Sao Paulo, Sao Paulo, Brazil. 8. National Institute of Developmental Psychiatry for Children and Adolescents, CNPq, Sao Paulo, Brazil. 9. Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina.
Abstract
BACKGROUND: Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE: To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS: This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS: Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION: These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.
BACKGROUND: Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatricpatients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation. OBJECTIVE: To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation. METHODS: This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI). RESULTS: Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas. CONCLUSION: These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.
Authors: Flavia Venetucci Gouveia; Jürgen Germann; Gabriel A Devenyi; Erich T Fonoff; Rosa M C B Morais; Helena Brentani; M Mallar Chakravarty; Raquel C R Martinez Journal: Front Hum Neurosci Date: 2021-06-09 Impact factor: 3.169