Amelioration of psychiatric symptoms through exposure to music individually adapted to brain rhythm disorders – a randomised clinical trial on the basis of fundamental research

From  Cogn Neuropsychiatry January 24 2014 

Wolf MülleraGünter HaffelderbAngelika Schlotmannc,Andrea T.U. Schaefersd & Gertraud Teuchert-Noodt*d

This pilot study examined, whether long-term exposure of psychiatric patients to music that was individually adapted to brain rhythm disorders associated with psychoticism could act to ameliorate psychiatric symptoms. A total of 50 patients with various psychiatric diagnoses were randomised in a 1:1 ratio to listen to CDs containing either music adapted to brain rhythm anomalies associated with psychoticism – measured via a specific spectral analysis – or standard classical music. Participants were instructed to listen to the CDs over the next 18 months. Psychiatric symptoms in both groups were assessed at baseline and at 4, 8 and 18 months, using the Brief Symptom Inventory (BSI). At 18 months, patients in the experimental group showed significantly decreased BSI scores compared to control patients. Intriguingly, this effect was not only seen for symptoms of psychoticism and paranoia but also for anxiety, phobic anxiety and somatisation. Exposure to the adapted music was effective in ameliorating psychotic, anxiety and phobic anxiety symptoms. Based on the theories of neuroplasticity and brain rhythms, it can be hypothesised that this intervention may be enhancing brain-rhythm synchronisation and plasticity in prefrontal-hippocampal circuits that are implicated in both psychosis/paranoia and anxiety/phobic anxiety.

Per gli Italiani:

Questo studio pilota esamina se l’esposizione a lungo termine di pazienti psichiatrici alla musica, adattata ai disordini del ritmo cerebrale associati con la psicosi, possa servire a migliorare i sintomi psichiatrici. Cinquanta pazienti con diagnosi psichiatriche di vario tipo sono stati assegnati in modo randomizzato a due gruppi e sottoposti a due condizioni sperimentali. Un gruppo ascoltava CD contenenti musica adattata alle anomalie cerebrali associate con la psicosi (misurate con analisi spettrale specifica), mentre l’altro ascoltava musica classica standard. Ai partecipanti è stato chiesto di ascoltare la musica per i successivi 18 mesi. I sintomi psichiatrici sono stati indagati in entrambi i gruppi prima dello studio e dopo 4, 8 e 18 mesi usando il test Brief Symptom Inventory (BSI). Dopo 18 mesi, i pazienti del gruppo sperimentale mostravano un punteggio BSI significativamente diminuito rispetto ai soggetti di controllo. Interessante osservare che questa diminuzione non è stata riscontrata solo per sintomi di psicosi e paranoia, ma anche per l’ansia, le fobie e la somatizzazione. Basandosi sulle teorie di neuroplasticità e dei ritmi cerebrali, gli Autori ipotizzano che questo intervento possa aumentare la sincronizzazione dei ritmi cerebrali e la plasticità dei circuiti prefrontali-ippocampali coinvolti sia nella paranoia, sia nella psicosi/paranoia, sia nell’ansia/fobia.


Valproic Acid for Perfect Pitch? Steady, Now…

FDA_seizure_drug_DepakoteFor the past few days, the internet has been abuzz with the announcement of the “perfect pitch miracle drug.” Let’s back up a bit, shall we?

Valproic acid has been used alone or in addition to other medications for nearly fifty years to treat epilepsy, and is the active ingredient in drugs such as Valproate and Depakon. It is also used in the prevention of migraines, mania in bipolar disorder and for the treatment of aggression exhibited in children with ADHD. It is in the class of anticonvulsants. To talk a little bit about how it works, our brain is made up of thousands of nerve cells that communicate back and forth via electrical signal, a very intricate and delicate process that need maintain a steady and stable balance for normative functioning. When repetitive and abnormally rapid electrical signals are released, this process becomes disturbed and over stimulated. Anticonvulsants such as Valproate function as a stabilizer by increasing the amount of the natural nerve-calming chemical GABA, (gamma-Aminobutyric acid), as an HDAC (histone deacetlyase) inhibitor (Monti et al., 2009). GABA is one of the brain’s chief inhibitory neurotransmitters, which many researchers believe to regulate anxiety. When the amount of GABA in the brain falls too low, Valproate prevents the breakdown of the chemical and works to stabilize the amount of electrical activity, which explains why the drug has been found effective as a treatment for periods of mania and epileptic seizures.

Unfortunately, valproic acid is far from the ideal end-all. Valproate has been known to potentially cause serious or life threatening damage to the liver, pancreas, and blood cells, and holds an alarmingly high statistic for weight gain. It is not approved for use during pregnancy and breastfeeding, and has recently been the target of a lawsuit due to unforeseen birth defects. It is also known to cause ataxia, thrombocytopenia and leucopenia, so before we all go rushing off to “increase our brain function,” it might be wise to spend a moment thinking critically.

This morning, Tom Ashbrook of On Point, NPR stated “Imagine a pill that could rewire your brain. Would make your brain young again. Able to learn and absorb like a five-year old. Music. Languages. Would you take it?”  Neuroplasticity has risen to near-celebrity status over the past few months, and recent study by Frontiers of Systems Neuroscience is certainly fanning the flame. Carried out by researchers from France, Canada, Maryland, Australia, Massachusetts and England, the study set out to discover whether such periods when enzymes “impose ‘brakes’ on neuroplasticity, might be able to “reopen critical periods of neuroplasticity” via a drug that blocks productions of those enzymes. Absolute pitch was thought to be a solid assessment of this possibility because there are “no known cases of an adult acquiring absolute pitch.”

Absolute pitch (AP) is the ability to identify or produce the pitch of a musical sound without any reference point. Individuals who possess AP, constituting about 0.01% of the general population, are able to identify the pitch class, i.e., one of the 12 notes of the Western musical system, e.g., C, D, G#, of a sound with great accuracy (varying between 70–99%, depending on the task, as compared to 10–40% for non-AP individuals, Takeuchi and Hulse, 1993). The study explains:

“Importantly, acquiring AP has a critical period (Levitin and Zatorre, 2003; Russo et al., 2003). A critical period is a fixed window of time, usually early in an organism’s lifespan, during which experience has lasting effects on the development of brain function and behavior. The principles of critical period phenomena and neural plasticity are increasingly well understood both at the behavioral/experiential (Kleim and Jones, 2008) and at the molecular/cellular level (Hensch, 2005). Specifically, behaviorally induced plasticity in the healthy brain, typically after the end of the relevant critical period, can lead to improvement beyond normal or average performance levels. However, for many tasks, this requires targeted training—simple routine use is often insufficient. The factors known to influence the efficiency of such targeted training include the number of repetitions involved, the intensity of the training as well as the relevance or saliency of the stimuli or task trained. Importantly, such training-induced learning is quite specific to the trained task and to the underlying brain networks, although some transfer to other, related domains of knowledge or skills is sometimes possible. At the cellular level, critical periods close when maturational processes and experiential events converge to cause neuoro-physiological and molecular changes that dampen or eliminate the potential for further change (Hensch, 2005Bavelier et al., 2010), thus imposing “brakes” on neuroplasticity. One of the epigenetic changes leading to decreased plasticity after the critical period involves the action of HDAC, an enzyme that acts as an epigenetic “brake” on critical-period learning (Morishita and Hensch, 2008Qing et al., 2008). Research has shown that inhibition of HDAC can reopen critical-period neuroplasticity in adult mice to enable recovery from amblyopia (Putignano et al., 2007Silingardi et al., 2010), and to facilitate new forms of auditory learning (Yang et al., 2012).” ( ).

The randomized, double blind study was conducted on twenty four men, half of which received Valproate and the other half, a placebo. The men who received Valproate showed advantage in pitch class identification. To come to the conclusion, it is imperative that we acknowledge the fact that these powerful pharmaceuticals were in no way developed for something so “trivial” of the acquisition of perfect pitch – the diagnostic simply was appropriate for a brief and extremely small study and subject pool. The researchers conclude:

If confirmed by future replications, our study will provide a behavioral paradigm for the assessment of the potential of psychiatric drugs to induce plasticity. In particular, the AP task may be useful as a behavioral correlate. If further studies continue to reveal specificity of VPA to the AP task (or to tasks on which training or intervention is provided), critical information will have been garnered concerning when systemic drug treatments may safely be used to reopen neural plasticity in a specific, targeted way.”

It is vital during this time of exponential and rapid advances in the realm of neuroscience that we keep the grounding measures of ethics and morality at the forefront of our minds. There is a reason performance enhancing drugs are strictly forbidden in competitive sports. While it is truly of great interest to deliberate over the implications of a drug altered to target neuroplasticity, with great power (all together now) comes great responsibility. 

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what should we do with our brain – a metaphorical critique

“The brain has always been described by means of technological metaphors.” [1]  neural pathways

One of the first handlings of this idiom occurred in Aristotle’s Rhetoric and Poetics: “Metaphor is the transference of a name from the object to which it has a natural application…” (Aristotle, Poetics, 21). More recently, individuals such as I.A. Richards, Kenneth Burke, and Max Black have made consequential advances in the field of metaphorical criticism, enabling its use to aid heavily in ornamentation and decoration, as structuring principle and discovery and description of the truth.[2]

According to Richards, all thought is metaphoric because when individuals attribute meaning, they are “simply seeing in one context an aspect similar to one [they] encountered in an earlier context.”[3] Though the work of theorists including Michael Osborn and Robert L. Ivie, we have a better understanding of how language relates us to reality, and how we as humans constitute reality through our use of symbols. When we process symbols to better understand reality, we are often using the metaphor. Phenomenological anomalies become accessible to us through the development of a physical materialism that often comes to life via symbols. When we attribute names or symbols to these phenomena, we are using the metaphor.

Along with the above, a number of others have stressed the importance of the metaphor. Nietzsche argued that it is simply the way in which we encounter the world: “A nerve-stimulus, first transformed into percept! First metaphor! The percept again copied into a sound! Second metaphor! And each time he leaps completely out of one sphere right into the midst of an entirely different one.”[4] In these viewpoints, metaphor occurs prior to and generates the discovery of ideas.

Foss explains a great example of this usage in Rhetorical Criticism: Exploration and Practice via the metaphor that “time is money.” By using terminology such as “I’ve invested a lot of time in someone,” “You need to budget your time” and “this gadget will save you time” we begin to equate time through a financial viewpoint; it now shares its level of worth with money. In metaphoric criticism, Max Black has developed an influential method known as interaction theory which juxtaposes two terms in the metaphor generally regarded to belong to two differing classes of experience. The first term is called the tenor, principal subject, or focus, while the second term is called the vehicle, secondary subject, or frame. For example, “The brain is a machine” is a metaphor for which brain is the tenor, and machine is the frame. The process from there then is to discriminate what traits are commonplace by the tenor and vehicle, and form a type of discerning argument. As the associated characteristics of the tenor and vehicle interact, some are accentuated while others are contained. As one goes through this progression of deconstructing tenor and vehicle of the metaphor, it becomes apparent that the metaphor serves an argumentative purpose: metaphor constitutes argument.[5]

To choose a common metaphor and artifact to further describe this process, the human brain has been the target of metaphoric assignments for quite some time: mirror, projector, computer, economy. (Tabbi, 1998) Others have termed the brain central telephone exchange, machine, and even government. While some illustrations appear more accurate than others, there are those who feel as a society that we’ve sorely missed the mark. In Catherine Malabou’s innovative work What Should We Do with Our Brain? (2008) she issues the challenge of deconstructing what we’ve always thought of our brains, and bestows an even greater one: what should we use it for?

Malabou begins the work by repetitiously stating “Our brain is plastic, and we do not know it.” The concept of consciousness is paramount to her: she not only calls attention to the many cities at work neurologically, but the fact that we do not know it. From “know thyself” forward, awareness has been the crux of academic and technological progress. Malabou’s critique of our neuronal dogma is an attempt not only to break away from the ideological presuppositions the field of neuroscience currently includes, but a call to become conscious of them-and of ourselves.

The first method of metaphoric criticism we may employ includes simply dissecting the metaphor. How does it function? In which way is Malabou trying to shake the current opinion of its role? Previously (as mentioned above) common symbols used for the brain include computer, central telephone exchange and machine. However, with Malabou’s concept of plasticity, the rigidity of these allegories will no longer suffice. Machines, computers and central telephone exchanges have a control center; an unyielding and stiff method of prescribing action and processing information. Plasticity is rigidity’s direct anonym, and as we have seen that metaphor not only tells a story but constitutes an argument, new metaphors must come into play. Our brains are no longer known to be entirely genetically determined, static or even simply flexible. “Plasticity, in effect, is not flexibility. Let us not forget that plasticity is a mechanism for adapting, while flexibility is a mechanism for submitting.”[6]  We must ascertain a new meaning, and this is Malabou’s challenge. She must use a metaphoric criticism to tear down the current views and instill the new.

We have now seen how the tenor and vehicle of “brain as machine” will no longer suffice. Let’s take a look at what Malabou uses as alternative: brain as plastic. Taken from the Greek plassein, to mold, plasticity has two basic definitions: one is to receive form, and one is to give form. “Plasticity in the nervous system means an alteration in structure or function brought about by development, experience or injury.”[7]Instead of mindlessly accumulating new metaphors for our brain, Malabou relies on the fact that we are the minds who make the metaphors, and sets out to explain just why the old metaphoric arguments won’t work. She offers perspective and a choice to the audience, just as Foss speaks of in Rhetorical Criticism, “If the audience finds the associated characteristics acceptable and sees the appropriateness of linking the two systems of characteristics, the audience accepts the argument.” In the context of modern day capitalism, Malabou creates a fantastic charge and call to consciousness, taking aide from European metaphysics, political engagement and neuroscience. By changing the terms (linguistically, semantically and literally) of the game, Malabou effectively provides a metaphoric critique to the prevailing comprehension of the function of the human brain.

In conclusion, a metaphoric criticism is best employed here simply because it is what the author employs herself. As Foss further states in Rhetorical Criticism, “Whatever metaphor is used to label and experience a phenomenon, then, suggests evaluations of it and appropriate behavior in response.” The old metaphors used suggest a worldview of a time passed, before the age of functional and real-time neurological imaging. The new formation of the model of our brain must be in line with the modern self: dynamic, transforming and revolutionary. We can no longer think of our brains, our neuronal selves, as but flexible and anonymous; as machine. We must affirm our capacity for change and confess our plasticity: evolutionary, adaptive, explosive. We must no longer consent to depression via disaffiliation; to be “blind to our own cinema.” Our brains tell us a story-whether we choose to listen or not. Karl Marx once stated “Humans make their own history, but they do not know that they make it.” As Malabou so eloquently proves throughout her work that a simple metaphor does not suffice and thus hinders a proper understanding for the plastic brain, she relies on concepts such as ecological, self-creating and emancipatory instead. Plasticity cannot be domesticated. The brain is ever-changing; so then must our conception of it be also.

“…At bottom, neuronal man has not known how to speak of himself. It is time to free his speech.”

-Catherine Malabou

[1] (Jeannerod, 2004).

[2] Foss, Sonja K. Rhetorical Criticism: Exploration and Practice, 2nd Ed. Prospect Heights: Waveland Press, 1996., p. 359

[3] Ibid, p. 359

[4] Friedrich Nietzsche, “On Truth and Falsity in their Ultramoral Sense,” in The Complete Works of Friedrich Nietzsche, ed. Oscar Levy, trans. Maximilian A. Mugge, II. New York: Macmillan, 1911., p. 178

[5] Foss, Sonja K. Rhetorical Criticism: Exploration and Practice, 2nd Ed. Prospect Heights: Waveland Press, 1996., p. 361

[6] Marc Jeannerod, 2004.

[7] See the entry “Plasticity in the Nervous System,” in The Oxford Companion to the Mind, ed. Richard L. Gregory (Oxford: Oxford University Press, 1987), 623.