Brain Stimulation for Memory. Mijail Misha D. Serruya, M.D., Ph.D. Outline. Definitions of memory and stimulation Macrostimulation Microstimulation Optical Challenges. Memory. Procedural. Semantic. Episodic Binding of item and context Spatial context & navigation - PowerPoint PPT Presentation
Brain Stimulation for MemoryMijail Misha D. Serruya, M.D., Ph.D.
OutlineDefinitions of memory and stimulationMacrostimulationMicrostimulationOpticalChallengesElectrical and optical stimulation of the brain can be used to modulate and enhance memory. First I will define what I mean by memory (eg episodic vs. semantic) and by stimulation (eg electrical vs. optical vs. chemical microfluidic, and macro- vs. micro-). I will then quickly mention non-invasive rTMS and tDCS techniques that have been investigated to enhance verbal episodic memory (Marshall et al., 2006). I will review the work of Andres Lozano and his colleagues regarding deep brain stimulation of basal forebrain and hypothalamic structures to enhance episodic memory (Laxton et al., 2010), and normalise glucose metabolic patterns, in patients with early Alzheimers disease, and Yitzhak Frieds recent work on direct electrical stimulation of entorhinal cortex to enhance spatial memory in humans (Suthana et al., 2012). I will next address the idea of using electrical stimulation to convey information, rather than merely buff up an existing circuit, by discussing the work of Sam Deadwyler and Ted Berger on the use of microstimulation in the hippocampus and prefrontal cortex reciprocally linked to computational models to restore memory behaviour in animal models (Berger et al., 2011). I will touch on Eb Fetz work on spike-triggered microstimulation to titrate plasticity of circuits linking spatially separate brain areas (Jackson et al., 2006). Finally I will review recent work using optogenetics to induce or incept memories of events that have not happened in animal models (Liu et al., 2012), cite optoelectronic devices (Wang et al., 2011), and how this work might be translated into a clinical useful medical device.What were the aims of the studies that the presentation is based on?The aim of most of the studies I just mentioned was to restore episodic memory; in the case of Lozanos work it is to enhance memory with an eye towards maintaining independent function in Alzheimers disease. In all the other cases, the restoration of memory is defined in the context of the specific tasks the investigators are employing with their human or non-human participants.What are the key areas of success or discussion?The first benchmark of success is if brain stimulation can restore well-defined episodic memory behaviour in an experimental setting. The next benchmark will be to describe how the particular brain stimulation technique in question can generalise to benefit other types of memory tasks in more naturalistic settings, and finally to patients with memory impairments to restore independence.What is your message to others in the field?Brain stimulation to restore and enhance memory is at a very early, pioneering stage of development. There are numerous types of memory we use, and they involve complex circuits throughout the brain; these structures and circuits can be compromised by a wide range of conditions including traumatic brain injury, stroke, and Alzheimers disease. While the first medical devices to be tested in humans will use deep brain macro-stimulation, the next generation of devices will use micro-stimulation, will incorporate closed-loop circuitry and integrated optoelectronics and autologous biological constructs. The devices I am describing are usually the province of functional neurosurgeons. That being said there are some ideas in the scientific literature discussing the possible incorporation of electronics INTO stents and other endovascular devices. While my talk for the conference wont focus on endovascular recording and stimulation to enhance memory, there is relevant scientific literature.Please outline some relevant studies for brain stimulation and their importance for neurointervnetionalistsEndovascular approaches for brain stimulation: plumber or electrician?
While interventional cardiologists have been using endovascular wires to electrically record and stimulate the specific regions of the heart for decades, this approach has barely been explored in the brain. The fact that ventricular nerves and parasympathetic plexus can be excited by endovascular electrodes (Sos et al., 2005; Diaz et al., 2006)provides proof-of-concept that direct electrical stimulation of brain structures could also be afforded via endovascular leads. Guide wires have already been used for intracranial electroencephalograpohic and evoked-potential recording (Stoeter et al., 1995). Such an approach offers the advantages of recording from areas that would be difficult to reach otherwise and spares the patient puncture or other trauma to brain parenchyma inevitable with open approaches. Beyond standard guide wires, investigation is under way to develop conducting nanowires that could be deployed using conventional endovascular techniques and yet could provide orders of magnitude greater numbers of recording channels (Watanabe et al., 2009).
Given recent work suggesting that deep brain electrical stimulation of entorhinal cortex (Suthana et al., 2012) or cholinergic forebrain structures (Laxton et al., 2010) can rapidly improve memory in humans, the outstanding questions for neurointerventionalists is whether such stimulation could be delivered through endovascular probes, and if so whether this would be a brief single intervention or deployment of a device chronically affixed endovascularly, as a stent incorporating active electronics. One could envision delivering direct electrical stimulation to entorhinal cortex, for example, via leads inserted through branches of the posterior communicating artery or conceivably the anterior choroidal artery in certain cases.
The natural starting point for exploring endovascular electrical recording and stimulation for memory in human patients, are in patients for whom stenting is already clinically indicated and who have or are expected to have memory deficits due to their neurovascular condition. A patient with premorbid mild cognitive impairment due to subcortical microangiopathic disease receiving a distal posterior cerebral artery stent to stabilise an aneurysm would be a prototypical candidate. Since electrical recording and stimulation has already been applied clinically for decades by cardiac interventionalists and electrophysiologists, the ground is set for enterprising neurointerventionalist physician-scientists to take up the gauntlet and pioneer endovascular brain stimulation and open a whole new range of possible treatments for neurological disease and injury.
Mijail Serruya is an assistant professor in the Department of Neurology at Jefferson Medical College, Philadelphia, USA
Berger TW, Hampson RE, Song D, Goonawardena A, Marmarelis VZ, Deadwyler SA. A cortical neural prosthesis for restoring and enhancing memory. J Neural Eng. 2011 Aug;8(4):046017.
Diaz A, Dardir N, Quan KJ. Electrical and hemodynamic function produced bystimulation of atropine sensitive right ventricular nerves in humans. J IntervCard Electrophysiol. 2006 Jun;16(1):45-9.
Jackson A, Mavoori J, Fetz EE. Long-term motor cortex plasticity induced by an electronic neural implant. Nature. 2006 Nov 2;444(7115):56-60.
Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, WherrettJ, Naglie G, Hamani C, Smith GS, Lozano AM. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol. 2010Oct;68(4):521-34.
Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature. 2012 Mar 22;484(7394):381-5. Marshall L, Helgadttir H, Mlle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3.
Sos P, Merkely B, Horvat PM, Zima E, Schauerte P. Determinants and effects ofelectrical stimulation of the inferior interatrial parasympathetic plexus during atrial fibrillation. J Cardiovasc Electrophysiol. 2005 Dec;16(12):1362-7.
Stoeter P, Dieterle L, Meyer A, Prey N. Intracranial electroencephalographicand evoked-potential recording from intravascular guide wires. AJNR Am JNeuroradiol. 1995 Jun-Jul;16(6):1214-7.
Suthana N, Haneef Z, Stern J, Mukamel R, Behnke E, Knowlton B, Fried I. Memory enhancement and deep-brain stimulation of the entorhinal area. N Engl J Med. 2012Feb 9;366(6):502-10. PubMed PMID: 22316444; PubMed Central PMCID: PMC3447081.
Wang J, Ozden I, Diagne M, Wagner F, Borton D, Brush B, Agha N, Burwell R,Sheinberg D, Diester I, Deisseroth K, Nurmikko A. Approaches to optical neuromodulation from rodents to non-human primates by integrated optoelectronic devices. Conf Proc IEEE Eng Med Biol Soc. 2011;2011:7525-8.
Watanabe H, Takahashi H, Nakao M, Walton K, Llins RR. Intravascular NeuralInterface with Nanowire Electrode. Electron Commun Jpn. 2009 Jul;92(7):29-37.
EpisodicBinding of item and contextSpatial context & navigationTemporal contextMental time travelSemantic
Do it as PICTURESPROCEDURAL NEO I KNOW HOW TO FLY A BLACK HAWK HELICOPTERVs EPISODIC, SCHWARZENNGER IN TOTAL RECALL REMEMBERS HIS DIFFERENT LIFE3StimulationNon-InvasiverTMS
tACS, tSOSImplantedElectricalEpidural/SubduralDepth/DBS/GridsLow impedance