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.

Future of Life Sciences: Top 10 List

The next wave of the biotechnology revolution is underway and promises to reshape the world in ways even more transformative than the agricultural, industrial, and information revolutions that preceded it.

It is not unimaginable that at some point, all biological processes, human and otherwise, could be understood and managed directly.

Here is a top ten list of key areas of contemporary advance in life sciences:

1. Synthetic Biology and Biotechnology 
2. Regenerative Medicine and 3D Printing 
3. Genomics, “Omics,” and Preventive Medicine 
4. Neuroscience 
5. Nanotechnology 
6. Big Health Data and Information Visualization 
7. Quantified Self (QS), Wearable Computing, and the Internet-of-Things (IOT) 
8. DIYscience, Citizen Science, Participatory Health, and Collective Intelligence 
9. Aging, Rejuvenation, Health Extension, and Robotics 
10. Space 

More information: Slideshare talk from the Max Planck Institute

Further advance in the integration of organic and inorganic matter

A fundamental research focus in nanotechnology is the deliberate creation of organic-inorganic hybrids such as rotaxanes that have the properties of both organic and inorganic matter. These nanomaterials can greatly extend the range of control and manipulation that can occur in nanomedicine and other applications.

One interesting recent example is engineered fusion proteins, inorganic-binding peptides conjugated with bioluminescence proteins. The fusion proteins can be used as bioimaging molecular probes both targeting minerals (through fluorescence labeling) and monitoring the rate of biomineralization (through induced reactions). (Yuca et al., Biotechnol Bioeng. 2011 May;108(5):1021-30.)

Figure 1. Integrating organic and inorganic materials: graphene sheet sandwiched in the hydrophobic interior of a phospholipid

Another example (Figure 1) is graphene sheets sandwiched in the hydrophobic interior of a phospholipid. The phospholipid layers of the membrane electrically isolate the embedded graphene from the external solution which means that the composite system could be used in the development of biosensors and bioelectronic materials. (Titov et al., ACS Nano. 2010 Jan 26;4(1):229-34.)

Advances in cytosolic drug delivery

Nanoparticles (particles smaller than 100 nm where materials display different properties than at the bulk state) are frequently used in nanomedicine for drug delivery and other purposes. The sophistication and specificity of nanoparticle use is growing, particularly for delivering drugs past the lipid bilayer barrier of the cell wall to the inside of cells (cytosolic drug delivery) where they can target biophysical processes more easily. Two advances focus on cytosolic drug delivery, using light and peptides to break the endosomes (carrying vehicles) to release drugs directly into the cytosol.

1) Light-mediated endosomal breakage
One advance is in the development of nanoparticles (size-tunable (30-200 nm) highly monodispersed mesoporous silica nanoparticles) that can be loaded with a variety of compounds and released into the cytosol via light-mediated endosomal breakage, as illustrated in Figure 1 (Febvay et al, Nano Lett, 2010).

Figure 1: Nanoparticle cargo discharge through light-activation.

2) GALA peptide endosomal breakage
A second advance is in cytosolic drug delivery with nanoparticles using a peptide, GALA, to encourage endosomal breakage. GALA (comprised of repeating sequences of Glu-Ala-Leu-Ala) mimics the function of viral fusion protein sequences that mediate escape of virus genes from endosomes (Nakase et al, Methods Mol Biol, 2011).

Foundations of bio-info tech convergence

The most important thing that became clear at last week’s 2nd annual Unither Nanomedical & Telemedical Technology Conference is that many different foundational technologies are starting to be in place for bio-info tech convergence. Ray Kurzweil and others herald the eventual re-engineering of humans into technology that can learn and evolve as fast as infotech but may not realize pathways for bio-info tech convergence are already underway.

Boundaries and definitions of organic and inorganic, natural and synthesized, biological and electronic are blurring into a variety of permutations.

It is almost becoming anachronistic to talk about bio-info convergence when the focus in some fields has already progressed to resolving the problems at hand with the available tools which may include any variety of organic, inorganic and hybrid models.

Three key areas with developments underway:

1. Nanoparticle drug delivery systems
With 5 million people receiving some sort of cancer radiation therapy worldwide each year, and cancer quickly becoming a major killer in developing as well as industrialized countries, improvements in diagnosis and treatment are sought. The nextgen standard could be nanoparticle drug delivery systems (diagnosis is still too challenging of a problem in comparison), which could be used independently or in combination with existing radiation technologies to ameliorate treatment. Many different types of nanoparticles (carbon nanotubes, calcium phosphate, gold and various magnetic nanoparticles) and related technologies such as minimally invasive nanoXrays are under development.

2. Implanted monitors and body area networking
The most obvious case of human-device integration is pacemakers (500,000 are implanted worldwide annually). The latest versions feature one-way broadcast with the devices communicating information externally to physicians for remote monitoring; wireless heart sensors currently have an installed base in the U.S. of over 150,000. Human wireless sensing is further conceptualized as body area networking, which mainly means sensors that are internal or external to the body transmitting data one-way. The IEEE working standard for this communication is 802.15.6. The next steps would be enabling two-way broadcast, bringing some light processing on-board the implanted or external body sensors and later, augmentation. Brain-computer interfaces (BCIs) are developing in lockstep.

3. Powering implants: one idea is the ATP chip
One of the biggest challenges with devices implanted in the body is energy; providing adequate ongoing power to the device. Power trumps the other two concerns: bandwidth and biocompatibility. Many interesting methods of power generation are being investigated including thermal and vibrational energy, RF, light/PV, biochemical energy and the ATP chip, possibly getting nanodevices to produce ATP from naturally circulating glucose.

Apparently no one is yet considering the human bacterial biome as a therapeutic or augmentation platform but this could be another interesting means of bio-info tech convergence.