ABSTRACT
The brain contains approximately 1010 neurons (comprising thousands of distinct species) that are connected through 1013synapses in a network comprising (cumulatively) 45 miles, with neurons (100 μm to 1 m in length) transmitting action potentials at velocities of from 2 to 400 km/h [4].Some of the core capacities to target for cognitive augmentation include enhanced synaptic velocity, learning ability, attentiveness, associative recall and memory, creativity, visualization, conceptualization, abstract thought, pattern recognition, judgment, interferential reasoning, sensory acumen, motor skills, and pain management. One area with recent findings is that of learning, where it was found that increases in the local availability of glucose molecules (the brain’s primary energy source) may assist in enhancing performance [5].Glucose has been shown to moderate the release of acetylcholine (a neurotransmitter implicated in attention) in the hippocampus, which impacts learning and memory at other sites in the brain, including the amygdala (which processes memory and emotional reactivity) and the medial septum (which is linked to the hippocampus and involved with spatial information processing) [6, 7]. The stimulant D-amphetamine was similarly observed to augment learning [8], and it is proposed that a rise in neuronal excitability may increase cortical plasticity with the effect of inducing synaptic sprouting and remodeling [9].Several types of neural nanomedical advances are now discussed, in the categories of nanopharmaceuticals, neural electrodes, brain-machine organic-inorganic interfacing, neural cell growth promotion, and the conceptual nanorobotic removal of neural lipofuscin. 41.2 NanopharmaceuticalsOne of the most direct ways to target neural pathologies and enhancement is through drugs, nanopharmaceuticals that enhance neurotransmitter activity and the biochemical environment of the brain. Nanopharmaceuticals interact with neuronal receptors, ion channels, nerve growth factors, and enzymes to increase neuronal stimulation, elevate the efficiency and sustainability of synaptic firing, and enhance the accessibility and localized delivery of neurotransmitters (e.g., acetylcholine, dopamine, glutamate,
norepinephrine, serotonin, and GABA (gamma-aminobutyric acid)). Nanopharmaceuticals may be helpful in pathology resolution, as well as enhancement functions such as the modulation of executive function, memory, mood, libido, appetite, and sleep. 41.2.1 Memory Management: Enhancing and BlockingOne familiar notion of memory enhancement is through the use of prescription drugs that boost focus and concentration: ADHD (attention-deficit hyperactivity disorder) medications like Modafinil, Ritalin, Concerta, Metadate, and Methylin [10], and amphetamines like Adderall, Dexedrine, Benzedrine, Methedrine, Preludin, and Dexamyl [10-12]. These drugs are controversial for several reasons, for example, while there is some documented augmentation 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 targeting of specific neural pathways, such as long-term potentiation induction and late-phase memory consolidation [13].A cholinesterase inhibitor, donepezil, which has shown modest benefits in cognition and behavior in the case of Alzheimer’s disease [14], was also seen to enhance the retention performance of healthy middle-aged pilots following training in a flight simulator [15]. Ampakines might also be helpful. They are benzamide compounds that augment alertness, sustain attention span, and assist in learning and memory where depolarizing AMPA receptors could enhance rapid excitatory transmission [16, 17]. Also helpful, could be the drug molecule MEM 1414, which 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 thought to be of benefit for neural enhancement because it generates other synapse-fortifying proteins [13, 18].Augmented memory management is not just enhanced remembering, but also the opposite, blocking or erasing unwanted memories such as trauma brought on by post-traumatic stress disorder (PTSD). Since even well-established memories require reconsolidation following retrieval, the memory reconsolidation process could be targeted by pharmaceuticals to disrupt or
erase aberrant memories [19]. Glutamate and b-adrenergic neurotransmitter receptors are critical to memory reconsolidation. These neurotransmitter receptors could be targeted by drug antagonists like scopolamine and propranolol, which bind with the receptors to induce amnestic effects, such that unwanted memories are destabilized on retrieval [20-23]. 41.2.2 Drug Delivery: Nanoparticles and Titanium
NanowiresDrug delivery remains a central focus in neural nanomedicine, encompassing many advances in nanoparticles in terms of refined multi-stage operation, extensively sustained performance, and precision targeting capabilities. Gulati et al. have developed a means of crossing the blood-brain barrier with a drug-releasing platform of nanoengineered titanium wires with titanium nanotube arrays. In vitro analysis demonstrated the successful release of neurotransmitters like DOPA (dopamine) and anticancer drugs like DOXO (doxorubicin) with release profiles spanning 6 h, and from one to several weeks [24]. 41.3 Neural ElectrodesAn important area of activity in neural nanomedicine is neural electrodes, electronic devices that are implanted into the brain to record electrical impulses and stimulate neurons. Clinical research using neural electrodes is helping to further characterize brain behavior. For example, Hart et al. measured the velocity of cortical activation with electrocorticography, to quantify visual object naming at 250-300 ms, and auditory word/object comprehension at 450-750 ms [25] (which is interesting in that visual object recognition was about twice as fast as auditory object comprehension). Other advances focus on the means of delivering and positioning neural electrodes. Kim et al. printed ultrathin flexible neural electrodes onto a bioresorbable silk fibroin (protein) substrate which dissolved when the electrode was applied to biological tissue. The electrode array then initiated a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface [26].
