We have conducted the largest prospective comparative study of laser amygdalohippocampotomy (SLAH), a minimally invasive procedure ablating the amygdalo-hippocampal complex (AHC) versus selective and standard open resection (OR) epilepsy surgery (N=425+). We demonstrated that SLAH is superior to OR in 1-year cognitive outcomes in adults (including episodic verbal memory & perceptual (semantic) recognition or name retrieval of objects/faces), while achieving comparable seizure control. We will extend our analysis longitudinally in an unprecedented manner (5-10 year outcome) leveraging this unique cohort of well-studied patients including neuropsychological (NP), structural and functional neuroimaging and seizure outcomes. We have also amassed a large sample of cases involving stereotactic laser ablation [SLA] of non-AHC structures. The heterogeneity of these SLA cases and the focal nature of the laser ablation surgical zones create an amazing opportunity for lesion-behavioral analyses. We will expand our neuroimaging analyses to include rigorous voxel lesion symptom mapping (VLSM) and novel methods of connectivity modeling with diffusion tensor imaging and resting state fMRI. We will focus on the neural circuitry responsible for declarative memory and language, while determining the optimal surgical zones to produce the best long-term cognitive and seizure outcomes. VLSM allows us to determine which temporal lobe regions are critical for specific cognitive functions, while connectivity analyses will reveal the interconnectedness of these regions in the individual patient (allowing us to determine the relative risk of decline at the patient level). Our preliminary findings indicate that: 1) SLAH patients exhibit unexpected improvement in multiple cognitive functions, which is unparalleled in their OR counterparts, and 2) SLA procedures sparing the AHC and broader medial TL regions frequently lead to severe decline in verbal memory/naming, particularly in cases of focal ablations of the language dominant temporal pole or fusiform gyrus. This suggests that verbal declarative memory depends upon a broad network extending beyond the AHC, which is a paradigm shift for surgical planning (i.e., regions thought to be expendable during surgical approach are actually critical to function). This knowledge is fundamentally important from mechanistic and clinical translational points of view, and our data and planned analyses provide a unique and feasible way to draw robust conclusions on these long-standing knowledge gaps. Our data raise pivotal questions about existing declarative memory models and the mechanism of recovery underlying the superior cognitive outcomes in many SLAH/SLA cases (e.g., functional sparing vs. reorganization), which we will address in this renewal by following our patients over time. Finally, while more epilepsy centers are employing SLA due to its improved cognitive outcomes, ultimate clinical adoption rests on seizure control, making it critical to determine SLAH efficacy over a longer time span.

Public Health Relevance

We carried out the largest prospective study of laser ablation and traditional open resection (OR) epilepsy surgery techniques using neuropsychological testing and neuroimaging completed at pre- and 1-year post- surgical time points (N=425+), and will now assess moderate term (5-10 year) outcome for all subjects with regards to seizure freedom, and cognitive and functional recovery (i.e., changes in ability to work, live independently). Preliminary data lead us to predict far better longitudinal cognitive and functional recovery for laser ablation patients, and has led us to question the validity of existing models of the brain regions involved in verbal memory and language. We will use advanced neuroimaging techniques to guide surgical practice (i.e., extent and location of ablation/resection) and outcome prediction at the level of the individual patient, while improving our knowledge of the neural circuits underlying cognition.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Acute Neural Injury and Epilepsy Study Section (ANIE)
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Whittemore, Vicky R
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Emory University
Schools of Medicine
United States
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Gross, Robert E; Stern, Matthew A; Willie, Jon T et al. (2018) Stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy. Ann Neurol 83:575-587
Inman, Cory S; Manns, Joseph R; Bijanki, Kelly R et al. (2018) Direct electrical stimulation of the amygdala enhances declarative memory in humans. Proc Natl Acad Sci U S A 115:98-103
Drane, Daniel L (2018) MRI-Guided stereotactic laser ablation for epilepsy surgery: Promising preliminary results for cognitive outcome. Epilepsy Res 142:170-175
Wen, Xuerong; Hartzema, Abraham; Delaney, Joseph A et al. (2017) Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model. BMC Pregnancy Childbirth 17:10
Meador, Kimford J; Loring, David W (2016) Developmental effects of antiepileptic drugs and the need for improved regulations. Neurology 86:297-306
Drane, Daniel L; Ojemann, Jeffrey G; Kim, Michelle S et al. (2016) Interictal epileptiform discharge effects on neuropsychological assessment and epilepsy surgical planning. Epilepsy Behav 56:131-8
Gross, Robert E; Willie, Jon T; Drane, Daniel L (2016) The Role of Stereotactic Laser Amygdalohippocampotomy in Mesial Temporal Lobe Epilepsy. Neurosurg Clin N Am 27:37-50
Drane, Daniel L; Loring, David W; Voets, Natalie L et al. (2015) In response: Naming and recognition after laser amygdalohippocampotomy: Is the hippocampus involved? Epilepsia 56:1318-9
Meador, Kimford J (2015) Decline of clinical research in academic medical centers. Neurology 85:1171-6
Drane, Daniel L; Loring, David W; Voets, Natalie L et al. (2015) Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy. Epilepsia 56:101-13

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