Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases

Abstract

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory.

Auras localized to the temporal lobe disrupt verbal memory and learning — Causal evidence from direct electrical stimulation of the hippocampus

“…Improvement in verbal memory was demonstrated with chronic hippocampal stimulation delivered in response to seizures and epileptiform activities using a responsive neurostimulation device (RNS) [7]. Studies with acute hippocampal stimulation have shown positive and negative effects on memory depending on stimulation frequencies (1–50 Hz versus > 100 Hz) and site of stimulation (hippocampal versus fornix stimulation) [8], [9], [10], [11]. Note that the stimulation in these studies did not induce a seizure, unlike our study.…”

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory

“…We discuss six aDES studies on memory modulation which provide a useful framework for considering the varying effects of hippocampal stimulation on memory performance (Coleshill et al, 2004;Fell et al, 2013;Koubeissi, Kahriman, Syed, Miller, & Durand, 2013;Lacruz et al, 2010;Miller et al, 2015;Suthana et al, 2012). These studies all used depth electrodes targeting the hippocampus, parahippocampal cortex, or fornix.…”

Brain Stimulation in Alzheimer’s Disease

“…One approach is to use other patient populations—where electrodes are already implanted for established clinical reasons—to test effect of stimulation on cognitive parameters impaired in AD, specifically episodic memory or spatial navigation. Indeed, such an approach has been employed in neurosurgical epilepsy patients by Suthana et al [9] where stimulation was applied in the entorhinal area during encoding and by Miller et al [10] with stimulation applied at the posterior fornix. Another approach is to conduct smaller adaptive trials where several therapeutic variables can be systematically altered.…”

“…These include stimulation protocols, as considerable variability can be seen even in the few memory trials conducted to date. For instance, Suthana et al [9] have used 50 HZ stimulation for 5 s on-off periods applied unilaterally, Miller et al [10] have used unilateral theta burst stimulation over longer period of times (20 min and more), and Laxton et al [2] have used continuous bilateral 130 Hz stimulation. At the same time, further animal experiments enabling more precise well-defined manipulation of neuronal circuits in disease models should be employed.…”