Case Series: Unilateral Amygdala Ablation Ameliorates Post-Traumatic Stress Disorder Symptoms and Biomarkers

Abstract

Background: Post-traumatic stress disorder is a severe psychobiological disorder associated with hyperactivity of the amygdala, particularly on the right side. Highly selective laser ablation of the amygdalohippocampal complex is an effective neurosurgical treatment for medically refractory medial temporal lobe epilepsy that minimizes neurocognitive deficits relative to traditional open surgery.

Objective: To examine the impact of amygdalohippocampotomy upon symptoms and biomarkers of post-traumatic stress disorder.

Methods: Two patients with well-documented chronic post-traumatic stress disorder who subsequently developed late-onset epilepsy underwent unilateral laser amygdalohippocampotomy. Prospective clinical and neuropsychological measurements were collected in patient 1. Additional prospective measurements of symptoms and biomarkers were collected pre- and post-surgery in patient 2.

Results: After laser ablation targeting the nondominant (right) amygdala, both patients experienced not only reduced seizures, but also profoundly abated post-traumatic stress symptoms. Prospective evaluation of biomarkers in patient 2 showed robust improvements in hyperarousal symptoms, fear potentiation of the startle reflex, brain functional magnetic resonance imaging responses to fear-inducing stimuli, and emotional declarative memory.

Conclusion: These observations support the emerging hypothesis that the right amygdala particularly perpetuates the signs and symptoms of post-traumatic stress disorder and suggests that focal unilateral amydalohippocampotomy can provide therapeutic benefit.

Keywords: Ablation; Amygdala; Anxiety; Epilepsy; Hippocampus; Lesion; Post-traumatic stress disorder; Resection.

FIGURE 1.

Stereotactic laser amygdalohippocampotomy in patient 1. A, Probe placement panels show initial laser probe location in approximately axial and sagittal trajectory views of T1-weighted sequence MRI. The probe is shown to pass from a right posterior approach through the anterior hippocampus to terminate in the amygdala. B, Thermography views show screenshots of real-time MR thermographic heat maps coregistered to anatomic images during ablation. Sequential steps of interstitial thermal ablation of the right amygdala, and anterior hippocampus, along a length of the laser probe are shown. C, Damage estimates demonstrate cumulative calculated irreversible damage zones (orange areas) in each trajectory plane. D, Ablation confirmation (T2-weighted inversion-recovery-sequence MRI) confirms the extent of final ablation in a standard coronal view. Arrows demarcate the rim of hyperintense edema surrounding the ablation zone.

FIGURE 2.

Stereotactic laser amygdalohippocampotomy in patient 2. A, Thermography views demonstrate probe location in approximately axial and sagittal trajectory views of T2-weighted inversion-recovery-sequence MRI. Coregistered thermographic heat maps display sequential real-time ablation of right amygdala and anterior hippocampus along a length of the laser probe. B, Damage estimates demonstrate cumulative calculated irreversible damage zones (orange areas) for individual ablation locations in each trajectory plane. C, Ablation confirmation (T2-weighted inversion-recovery) shows the extent of final ablation in trajectory and standard coronal views. Arrows demarcate the rim of hyperintense edema surrounding the ablation zone.

FIGURE 3.

Clinical PTSD outcome following ablation. A, Total PTSD symptoms as measured by the Clinician-Administered PTSD Scale (CAPS-5) in patient 2. B, PTSD symptom clusters breaks down the total PTSD scores at each time point to symptom domains measured by the CAPS-5, referred to as criteria B, C, D, and E. C, D, and E are postablation changes in PTSD-related markers.

FIGURE 4.

Postablation changes in PTSD-related neural activations. Changes in activation at 4 regions of interest (left amygdala, right amygdala, ventromedial prefrontal cortex, and dorsal anterior cingulate cortex) from presurgery to 6 mo postsurgery in patient 2. Region of interest boundaries are demonstrated on coronal and sagittal slices, as well as the ablation extent overlaid on the right amygdala region of interest.

FIGURE 5.

Change in fear-potentiated startle responses following amygdala ablation. Change is demonstrated from presurgery to 6 mo postsurgery in response to the conditioned stimulus paired with noxious stimulus (CS+) and to the conditioned stimulus not paired with noxious stimulus (CS-).

FIGURE 6.

Postablation change in emotional memory. Change in emotional memory from presurgery to 6 mo postsurgery in terms of the ratings subjective arousal and proportion of images recalled for negative, neutral, and positive images presented from the International Affective Picture System (IAPS).