Cognitive Enhancement Memory Management: Retrieval and Blocking

One familiar notion of cognitive enhancement is prescription drugs that boost focus and concentration: ADHD (attention-deficit hyperactivity disorder) medications like Modafinil, Ritalin, Concerta, Metadate, and Methylin [1], and amphetamines like Adderall, Dexedrine, Benzedrine, Methedrine, Preludin, and Dexamyl [1-3]. These drugs are controversial as while there is some documented benefit, there is also a recovery period (implying that sustained use is not possible), and they are often obtained illegally or for nonmedical use.

What is new in memory enhancement drug development is the possibility of targeting specific neural pathways, like long-term potentiation induction and late-phase memory consolidation [4]. A cholinesterase inhibitor, donepezil, which has shown modest benefits in cognition and behavior in the case of Alzheimer’s disease [5], was also seen to enhance the retention performance of healthy middle-aged pilots following training in a flight simulator [6]. Ampakines are benzamide compounds that augment alertness, sustain attention span, and assist in learning and memory (by depolarizing AMPA receptors to enhance rapid excitatory transmission) [7, 8]. The drug molecule MEM 1414 activates an increase in the production of CREB (the cAMP response element-binding protein) by inhibiting the PDE-4 enzyme, which typically breaks it down. Higher CREB production is good for neural enhancement because it generates other synapse-fortifying proteins [4, 9].

Memory management in cognitive enhancement could also include blocking or erasing unwanted memories such as traumatic memories brought on by PTSD (post-traumatic stress disorder). Since even well-established memories require reconsolidation following retrieval, the memory reconsolidation process could be targeted by pharmaceuticals to disrupt or even erase aberrant memories [10]. Critical to memory reconsolidation are the glutamate and b-adrenergic neurotransmitter receptors. These neurotransmitter receptors could be targeted by drug antagonists like scopolamine and propranolol, which bind with these receptors, to induce amnestic effects so that unwanted memories are destabilized on retrieval [11-14].

Summarized from: Boehm, F. Nanomedical Device and Systems Design: Challenges, Possibilities, Visions. CRC Press, 2013. Ch17.
Full article: Nanomedical Cognitive Enhancement  

References:
[1] Weyandt, L.L., Janusis, G., Wilson, K.G., Verdi, G., Paquin, G., Lopes, J., Varejao, M., and Dussault, C., Nonmedical prescription stimulant use among a sample of college students: Relationship with psychological variables. J. Atten. Disord. 13(3), 284–296, 2009.
[2] Varga, M.D., Adderall abuse on college campuses: A comprehensive literature review. J. Evid. Based Soc. Work 9(3), 293–313, 2012.
[3] Teter, C.J., McCabe, S.E., LaGrange, K., Cranford, J.A., and Boyd, C.J., Illicit use of specific prescription stimulants among college students: Prevalence, motives, and routes of administration. Pharmacotherapy 26(10), 1501–1510, 2006.
[4] Farah, M.J., Illes, J., Cook-Deegan, R., Gardner, H., Kandel, E., King, P., Parens, E., Sahakian, B., and Wolpe, P.R., Neurocognitive enhancement: What can we do and what should we do? Nat. Rev. Neurosci. 5(5), 421–425, 2004.
[5] Steele LS, Glazier RH (April 1999). "Is donepezil effective for treating Alzheimer's disease?". Can Fam Physician 45: 917–9. PMC 2328349. PMID 10216789.
[6] Yesavage, J.A., Mumenthaler, M.S., Taylor, J.L., Friedman, L., O’Hara, R., Sheikh, J., Tinklenberg, J., and Whitehouse, P.J., Donepezil and flight simulator performance: Effects on retention of complex skills. Neurology 59(1), 123–125, 2002.
[7] Chang, P.K., Verbich, D., and McKinney, R.A., AMPA receptors as drug targets in neurological disease—Advantages, caveats, and future outlook. Eur. J. Neurosci. 35(12), 1908–1916, 2012.
[8] Arai, A.C. and Kessler, M., Pharmacology of ampakine modulators: From AMPA receptors to synapses and behavior. Curr. Drug Targets 8(5), 583–602, 2007.
[9] Solomon, L.D., The Quest for Human Longevity: Science, Business, and Public Policy. Transaction Publishers, New Brunswick, NJ, 2006, 197pp.
[10] Milton, A.L. and Everitt, B.J., The psychological and neurochemical mechanisms of drug memory reconsolidation: Implications for the treatment of addiction. Eur. J. Neurosci. 31(12), 2308–2319, 2010.
[11] Debiec, J. and LeDoux, J.E., Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience 129, 267–272, 2004.
[12] Lee, J.L.C., Milton, A.L., and Everitt, B.J., Reconsolidation and extinction of conditioned fear: Inhibition and potentiation. J. Neurosci. 26, 10051–10056, 2006.
[13] Ferry, B., Roozendaal, B., and McGaugh, J.L., Role of norepinephrine in mediating stress hormone regulation of long-term memory storage: A critical involvement of the amygdala. Biol. Psychiatry 46, 1140–1152, 1999.
[14] Sara, S.J., Roullet, P., and Przybyslawski, J., Consolidation of memory for odor-reward association: á-adrenergic receptor involvement in the late phase. Learn. Mem. 6, 88–96, 1999.