Change the Music

 

‘Change the music’ –

Psychotherapy and microtubule vibrations

October 21, 2014

 

Commentary on: Lane et al, Memory reconsolidation, emotional arousal and the process of change in psychotherapy: New insights from brain science

 

In their BBS Target Article, Lane et al (2014) recommend eliciting traumatic memory with concomitant positive emotional experience to ‘re-consolidate’ an alternative memory, over-writing, if not erasing the trauma, leading to psychotherapeutic benefit. In this worthy effort the authors claim new insight from brain science, but lack (as does mainstream science in general) actual neurobiological mechanisms for emotional experience (consciousness), and memory (encoding, consolidation/re-consolidation, storage and recall). When asked why he robs banks, the notorious criminal Willie Sutton famously answered: “because that’s where the money is!” To delete or over-write traumatic memories, we need to know where and how they are encoded and consolidated. And improving conscious experience (an essential therapeutic goal) might be far easier if we knew how it was mediated. It is my contention (definitely a minority contention, but one supported by evidence) that in contrast to conventional wisdom, both memory and consciousness are rooted inside brain neurons, in vibrational states of microtubules.

 

Mainstream science considers consciousness to emerge from complex computation among brain neurons, each acting as fundamental units of information. But such views lack specifics and fail to generate testable predictions. Moreover, single cell organisms such as paramecia exhibit complex cognition (e.g. finding food and mates, sex and learning) without synaptic connections, using their cytoskeletal microtubules. These same microtubules are found inside brain neurons, as major components of the cytoskeleton, self-assembling to shape neurons and regulate synapses. They are lattice polymers of tubulin, the brain’s most prevalent protein, and theorized to process and store information (Hameroff and Watt, 1982; Rasmussen at al, 1990). Microtubule disruption, e.g. in Alzheimer’s disease, correlates with cognitive dysfunction.

 

A maverick theory of consciousness (Penrose-Hameroff ‘orchestrated objective reduction’, ‘Orch OR’, e.g. Penrose and Hameroff, 1995; Hameroff and Penrose, 2014) suggests quantum vibrational computations in microtubules inside brain neurons 1) produce conscious experience, and 2) regulate neuronal firings and synaptic plasticity. In Orch OR, microtubule quantum vibrations are ‘orchestrated’ (‘Orch’) by synaptic inputs and memory (encoded in microtubules), and terminated by ‘objective reduction’ (‘OR’), Penrose’s solution to the measurement problem in quantum mechanics (Penrose, 1989). Orch OR has been viewed skeptically and harshly criticized, as the brain has been considered too ‘warm, wet and noisy’ for seemingly delicate quantum effects. But in recent years warm quantum biology has been recognized in photosynthesis, bird navigation, olfaction, and in microtubules.

 

Quantum resonant vibrations in megahertz and kilohertz frequencies have been discovered in single isolated microtubules, and bundles of microtubules inside active neurons (Sahu et al, 2013a; 2013b; Ghosh et al, 2014), validating Orch OR’s biological plausibility. Orch OR now further suggests microtubule vibrations (e.g. in megahertz) interfere to cause music-like (electrophysiological) ‘beats’ seen as EEG rhythms (Hameroff and Penrose, 2014). Indeed, microtubule resonant vibrations have been likened to music, specifically anharmonic Indian Raga (Ghosh et al, 2014). Recent evidence also shows that anesthetics (which selectively erase consciousness) act on microtubules, rather than membrane receptors as is generally assumed (Emerson et al, 2013). The maverick Orch OR theory has far more supportive evidence than do any mainstream approaches to consciousness. 

 

Memory is generally attributed to synaptic plasticity, but synaptic components are transient, and yet memories can last lifetimes. Again, microtubules play key roles, as synapses are formed, maintained and regulated by microtubules and associated proteins. In long term potentiation (‘LTP’, a cellular model for memory), calcium influx activates CaMKII, a hexagonal holoenzyme which then extends sets of 6 kinase domains (each domain able to phosphorylate a substrate). The CaMKIIs rapidly distribute to microtubules throughout dendritic trees, and (somehow) encode memory, presumably by phosphorylation (Lemieux et al, 2012). On each CaMKII, 6 kinase domains can bind (and phosphorylate) precisely 6 tubulins in microtubule hexagonal lattices, and can encode 6 ‘bits’ of memory per CaMKII (Craddock et al, 2012) onto dendritic microtubules which are uniquely stable and ideally positioned to encode memory. CaMKII phosphorylation of specific tubulins  would modulate microtubule resonant vibrations like frets or nodes in a musical instrument, encoding memory, changing the tune and altering conscious experience.

 

In a psychotherapy paradigm roughly similar to that proposed for human subjects by Lane et al, Cao et al (2008) elicited specific fear memories in mice, and then transiently overexpressed CaMKII, erasing (or over-writing) the fear memory. CaMKII overexpression presumably increased memory turnover, but required invasive genetic manipulation.

 

It may be possible to noninvasively stimulate memory turnover (and mood enhancement) by direct effects on brain microtubules. The action of antidepressants, e.g. fluoxitene (Prozac) appears to involve restructuring of cytoskeletal microtubules over several weeks (Bianchi et al, 2009). More immediate effects may be addressed through non-invasive transcranial modalities. Among these are transcranial magnetic stimulation (‘TMS’), transcranial electrical, direct current stimulation (‘TDcS’) and transcranial ultrasound stimulation (‘TUS’). But only TUS can be narrowly focused to target specific, deeper brain regions (Legon et al, 2014). TUS consists of megahertz mechanical vibrations which, at low intensity, sub-thermal levels, safely penetrate skull and brain. As microtubules have megahertz vibrational resonances, TUS with proper settings might be expected to enhance microtubule resonance, and thereby affect cognition and mental states. Indeed, focused TUS enhanced sensory discrimination in human volunteers (Legon et al, 2014), and unfocused TUS improved mood in chronic pain patients (Hameroff et al, 2013).

 

To erase or over-write traumatic memory, to change the music and re-tune the tubules, combinations of pharmacology, psychotherapy and TUS (e.g. aimed at microtubule vibrations in amygdala, hippocampus and pre-frontal cortex) may be optimal. As the Beatles sang, “Take a sad song and make it better”.

 

 

References

Bianchi M, Shah AJ, Fone KC, Atkins AR, Dawson LA, Heidbreder CA, et al (2009). Fluoxetine administration modulates the cytoskeletal micro-tubular system in the rat hippocampus. Synapse 63:359–64.

 

Cao X, Wang H, Mei B, An S, Yin L, Wang P, Tsien JZ (2008) Inducible and Selective Erasure via Chemical-Genetic Manipulation. Neuron 60: 353–366.

 

Craddock T, Tuszynski J, Hameroff S (2012) Cytoskeletal signaling: is memory encoded in microtubule lattices by CaMKII phosphorylation? PLoS Comput Biol 8(3):e1002421.

 

Emerson D, Weiser B, Psonis J, Liao Z, Taratula O, Fiamengo A, et al (2013) Direct modulation of microtubule stability contributes to anthracene general anesthesia. J Am Chem Soc 2013;135(14):5398.

 

Ghosh S, Aswani K, Singh S, Sahu S, Fujita D, Bandyopadhyay A (2014) Design and Construction of a Brain-Like Computer: A New Class of Frequency-Fractal Computing Using Wireless Communication in a Supramolecular Organic, Inorganic System  Information 5(1):28-100 doi:10.3390/info5010028

 

Hameroff S, Penrose R (2014) Consciousness in the universe – Review of the Orch OR theory. Phys Life Rev http://www.sciencedirect.com/science/article/pii/S1571064513001188

 

Hameroff SR, Watt RC (1982) Information processing in microtubules. J Theor Biol 98:549–61.

informationprocessing_hameroff_watt 1982.pdf (271.46 KB)

 

Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, et al (2013) Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul 3(6):409–15.

 

Lane RD, Ryan L, Nadel L, Greenberg L (2013) Memory Reconsolidation, Emotional Arousal and the Process of Change in Psychotherapy: New Insights from Brain Science Behavioral and Brain Science, in press

 

Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ (2014) Nature Neuroscience 17: 322–329

 

Lemieux M, Labrecque S, Tardif C, Labrie-Dion E, Lebel E, De Koninck P (2012) Translocation of CaMKII to dendritic microtubules supports the plasticity of local synapses. J Cell Biol: 198(6):1055-73

 

Penrose R (1989) The emperor’s new mind Oxford: Oxford University Press

 

Penrose R, Hameroff SR (1995) What gaps? Reply to Grush and Churchland. J Conscious Stud 2:98–112

 

Rasmussen S, Karampurwala H, Vaidyanath R, Jensen K, Hameroff S (1990) Computational connectionism within neurons: a model of cytoskeletal automata subserving neural networks. Physica D 42:428–49.

 

Sahu S, Ghosh S, Ghosh B, Aswani K, Hirata K, Fujita D, et al (2013) Atomic water channel controlling remarkable properties of a single brain microtubule: correlating single protein to its supramolecular assembly. Biosens Bioelectron 47:141–8.

 

Sahu S, Ghosh S, Hirata K, Fujita D, Bandyopadhyay A (2013) Multi-level memory-switching properties of a single brain microtubule. Appl Phys Lett 102:123701.

 

 

 

Stuart Hameroff MD

Departments of Anesthesiology and Psychology

Center for Consciousness Studies

The University of Arizona, Tucson, Arizona