ReviewDeep brain stimulation for enhancement of learning and memory
Introduction
Episodic memory, or the ability to remember personal experienced events, is severely compromised in various neurological disorders affecting the medial temporal lobe (MTL) including Alzheimer's disease, temporal lobe epilepsy, traumatic brain injury and other MTL injuries such as those occurring during stroke, cardiac arrest, or encephalitis. While deep brain stimulation (DBS) has been used to successfully treat movement disorders such as Parkinson's disease and dystonia, an exciting new frontier of DBS is the enhancement of cognitive function, and memory in particular. The implications of such enhancement to patients affected with disorders of memory may be of great significance. In the current review, we summarize several studies illustrating the potential for DBS or cortical surface stimulation to enhance episodic learning and memory. We also discuss and propose several future directions that would provide necessary insight as to whether DBS could be useful for treating memory disorders.
Section snippets
DBS of the MTL circuit enhances memory
In achieving potential enhancement of memory function by stimulation, understanding MTL circuitry is of critical importance since the ability to form episodic memories critically depends on this structure (Eichenbaum, 2000; for review see Squire et al., 2004). The human MTL consists of several functionally and structurally distinct areas including the hippocampus, amygdala, and adjacent parahippocampal, entorhinal, and perirhinal cortices. The hippocampus is comprised of even smaller
Temporal specificity of effects
Overall, an important aspect of memory enhancing DBS would be its application at a specific phase of information processing, namely during the learning, recall, or consolidation phase. Evidence from neurorehabilitation studies (Murphy and Corbett, 2009) suggests that therapeutic intervention would be ideal if used in an as-needed basis such as during learning or recall. Perhaps similarly, DBS may have larger effects depending on whether it is applied during learning (encoding), recall
Underlying neurophysiological mechanism of action
How does memory enhancing DBS affect neuronal activity at the site of delivery? Most clinical DBS studies, such as those for Parkinson's disease, stimulate nuclei or areas of gray matter. While some studies suggest that DBS of gray matter suppresses the activity of nearby neurons, others suggest that it excites afferent and/or efferent axonal projections (for review see McIntyre et al., 2004). Studies using simultaneous electrical stimulation, electrophysiology and fMRI have shown that
Generalization of effects
Thus far, studies showing DBS-related enhancement of human memory have mostly been carried out in epilepsy patients who need implantation of intracranial depth electrodes for clinical reasons. Therefore, the question remains as to whether DBS effects on memory can in fact be generalizable and extend to other patient populations (e.g. traumatic brain injury and Alzheimer's disease). Theta-frequency DBS administered to the medial septal nucleus increased hippocampal theta and improved spatial
Future directions in neuroenhancement of memory
DBS technology has the potential for significant improvement in the future. For example, a DBS system that incorporates feedback from simultaneous recording electrodes such as those recording oscillatory patterns or single neuron activity will provide more sophisticated stimulation protocols (e.g. Berger et al., 2011). Controllable DBS systems that do not utilize continuous stimulation but instead provide on-demand stimulation during periods of critical information processing may also be of
Summary and conclusions
Overall, it is necessary that future studies build upon and elucidate the mechanism of action used in DBS enhancement of memory. Clearly, the location, parameters, and phase of delivery of DBS are quite variable across studies. Thus, systematic comparisons and consistent methodologies across future studies will contribute to the understanding of DBS and its effects on learning and memory and whether it will be a useful therapeutic treatment for patients with memory disorders.
Acknowledgments
This work was supported by the National Institute of Neurological Disorders and Stroke (NS033221) and the Dana Foundation.
References (81)
- et al.
Deep brain stimulation, vagal nerve stimulation and transcranial stimulation: an overview of stimulation parameters and neurotransmitter release
Neurosci. Biobehav. Rev.
(2009) - et al.
Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease
Brain Stimul.
(2012) - et al.
Human hippocampal neurons predict how well word pairs will be remembered
Neuron
(2001) - et al.
Electric stimulation fMRI of the perforant pathway to the rat hippocampus
Magn. Reson. Imaging
(2008) - et al.
The functional role of cross-frequency coupling
Trends Cogn. Sci.
(2010) - et al.
Visual memory improved by non-invasive brain stimulation
Brain Res.
(2010) - et al.
Single neuron activity in human hippocampus and amygdala during recognition of faces and objects
Neuron
(1997) A mechanism for cognitive dynamics: neuronal communication through neuronal coherence
Trends Cogn. Sci.
(2005)- et al.
Recall deficits produced by afterdischarges in the human hippocampal formation and amygdala
Electroencephalogr. Clin. Neurophysiol.
(1985) - et al.
Human medial temporal-lobe stimulation disrupts both formation and retrieval of recent memories
Brain Cogn.
(1985)
Memory rescue and enhanced neurogenesis following electrical stimulation of the anterior thalamus in rats treated with corticosterone
Exp. Neurol.
Theta returns
Curr. Opin. Neurobiol.
Single pulse electrical stimulation of the hippocampus is sufficient to impair human episodic memory
Neuroscience
Transcranial brain stimulation studies of episodic memory in young adults, elderly adults and individuals with memory dysfunction: a review
Brain Stimul.
Deep brain stimulation for treatment-resistant depression
Neuron
Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both
Clin. Neurophysiol.
Transcranial direct current stimulation: State of the art 2008
Brain Stimul.
Electrical stimulation in anterior limbs of internal capsules in patients with obsessivecompulsive disorder
Lancet
Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients
Seizure
The basic mechanism for the electrical stimulation of the nervous system
Neuroscience
Post-training intracranial self-stimulation facilitates a hippocampus-dependent task
Behav. Brain Res.
Electrical stimulation of neural tissue to evoke behavioral responses
J. Neurosci. Methods
The Hippocampal Formation
Hippocampal Formation
Changes in apraxia after deep brain stimulation of the nucleus basalis Meynert in a patient with Parkinson dementia syndrome
Mov. Disord.
Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson's disease
Appl. Neurophysiol.
A cortical neural prosthesis for restoring and enhancing memory
J. Neural. Eng.
Stimulation of perforant path fibers induces LTP concurrently in amygdala and hippocampus in awake freely behaving rats
Neural. Plast.
Temporal lobe cortical electrical stimulation during the encoding and retrieval phase reduces false memories
PLoS One
Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory
Hippocampus
Enhanced recognition memory following vagus nerve stimulation in human subjects
Nat. Neurosci.
Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys
J. Neurophysiol.
Globus pallidus stimulation activates the cortical motor system during alleviation of Parkinsonian symptoms
Nat. Med.
The Human Hippocampus. Fuctional Anatomy, Vascularization, and Serial Sections with MRI
A cortical-hippocampal system for declarative memory
Nat. Rev. Neurosci.
Memory modulation by weak synchronous deep brain stimulation: a pilot study
Brain Stimul.
Medial temporal theta state before an event predicts episodic encoding success in humans
Proc. Natl. Acad. Sci. U. S. A.
Memory enhancement induced by hypothalamic/fornix deep brain stimulation
Ann. Neurol.
A nonlinear model for hippocampal cognitive prosthesis: memory facilitation by hippocampal ensemble stimulation
IEEE Trans. Neural. Syst. Rehabil. Eng.
Stimulate or degenerate: deep brain stimulation of the nucleus basalis Meynert in Alzheimer dementia
World Neurosurg.
Cited by (96)
Neurophysiological mechanisms of cognition in the developing brain: Insights from intracranial EEG studies
2023, Developmental Cognitive NeuroscienceFuture avenues for education and neuroenhancement
2021, New Ideas in PsychologyNon-invasive vagal nerve stimulation decreases brain activity during trauma scripts
2020, Brain StimulationCitation Excerpt :Secondly, the decreased inflammatory response with VNS appears to result from NTS mediated activation of the dorsal motor nucleus and subsequent efferent pathway activation to the celiac ganglion, inhibiting cytokine production from the spleen [31]. In addition, VNS appears to improve memory when applied during learning [32–34], potentially through increased sensory gating or effects on neuroplasticity [35]. New non-invasive transcutaneous VNS (nVNS) devices have been developed that are safe, cost-effective, and portable, potentially facilitating broader adoption (e.g., at-home) and thus eliminates some of the previous limitations of implantable VNS such as high cost, surgery, and introduction of a foreign object into the patient [36,37].