Intracortical Recording Devices

A key future use of neural electrode technology envisioned for nanomedicine and cognitive enhancement is intracortical recording devices that would capture the output signals of multiple neurons that are related to a given activity, for example signals associated with movement, or the intent of movement. Intracortical recording devices will require the next-generation of more robust and sophisticated neural interfaces combined with advanced signal processing, and algorithms to properly translate spontaneous neural action potentials into command signals [1]. Capturing, recording, and outputting neural signals would be a precursor to intervention and augmentation.

Toward the next-generation functionality necessary for intracortical recording devices, using organic rather than inorganic transistors, Bink et al. demonstrated flexible organic thin film transistors with sufficient performance for neural signal recording that can be directly interfaced with neural electrode arrays [2].

Since important brain network activity exists at temporal and spatial scales beyond the resolution of existing implantable devices, high-density active electrode arrays may be one way to provide a higher-resolution interface with the brain to access and influence this network activity. Integrating flexible electronic devices directly at the neural interface might possibly enable thousands of multiplexed electrodes to be connected with far fewer wires. Active electrode arrays have been demonstrated using traditional inorganic silicon transistors, but may not be cost-effective for scaling to large array sizes (8 × 8 cm).

Also, toward neural signal recording, Keefer et al. developed carbon nanotube coated electrodes, which increased the functional resolution, and thus the localized selectivity and potential influence of implanted neural electrodes. The team electrochemically populated conventional stainless steel and tungsten electrodes with carbon nanotubes which amplified both the recording of neural signals and the electronic stimulation of neurons (in vitro, and in rat and monkey models). The clinical electrical excitation of neuronal circuitry could be of significant benefit for epilepsy, Parkinson’s disease, persistent pain, hearing deficits, and depression. The team thus demonstrated an important advance for brain-machine communication: increasing the quality of electrode-neuronal interfaces by lowering the impedance and elevating the charge transfer of electrodes [3].

Full Article: Nanomedical Cognitive Enhancement

References:
[1] Donoghue, J.P., Connecting cortex to machines: Recent advances in brain interfaces. Nat. Neurosci. 5 (Suppl), 1085–1088, 2002.
[2] Bink, H., Lai, Y., Saudari, S.R., Helfer, B., Viventi, J., Van der Spiegel, J., Litt, B., and Kagan, C., Flexible organic electronics for use in neural sensing. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 5400–5403, 2011.
[3] Keefer, E.W., Botterman, B.R., Romero, M.I., Rossi, A.F., and Gross, G.W., Carbon nanotube coating improves neuronal recordings. Nat. Nanotechnol. 3(7), 434–439, 2008.

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.

What are Cognitive Nanorobots?

Cognitive nanorobots are an extension of the more familiar idea of medical nanorobots.

Medical nanorobots are a range of medical solutions using nanoscale electronics. Medical nanorobots span the continuum from nanoparticles in current pharmaceutical use that disgorge cargo in cellular destinations per simple onboard logic instructions to optically-stimulated channelrhodopsin proteins for real-time live biological intervention to the more elaborate conceptualization of many species of future medical nanorobots such as respirocytes, clottocytes, vasculoids, and microbivores that could perform a variety of biophysical clean-up, maintenance, and augmentation functions in the body.

In the most basic sense, cognitive nanorobots are the analog to medical nanorobots, nanorobots deployed in the specific context of facilitating, aiding, and improving the processes of cognition like perception and memory, a sort of NanoNeuroProsthetics.

Cognition is just another biological function, a process that can possibly be identified, managed, and ameliorated. Robert Freitas in the Nanomedicine text books has already begun to explore the issue of nanorobot biocompatibility with neural cells, and outlined the different levels of concern and response for them: mechanical, physiological, immunological, cytological, and biochemical.

In summary, one initial way to consider and classify cognitive nanorobots is as a special case of medical nanorobots.

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