Highlights:

• Psychiatry 3.0 has both therapeutic and diagnostic applications

• Maps onto pre-existing frameworks

• Robust evidence base

• Value proposition is risk minimized

The notion of a Psychiatry 3.0 was mentioned in an article about “Jolting brain circuits with electricity…”

The metaphor is useful:

• Psychiatry 1.0: Psychodynamic Psychotherapy and Psychoanalysis, subsequently continuing and/or forking into related specialized schools of thoughts. E.g., Humanistic psychology, Gestalt psychology, Behaviorism, etc..

• Psychiatry 2.0: Psychopharmacology boom, beginning with Thorazine in the 1950s and expanding into the variety of psychotropic classes. E.g., 1st & 2nd generation antipsychotics, selective serotonin reuptake inhibitors (SSRIs), stimulants, etc.

• Psychiatry 3.0: Targeted stimulation of neuro-circuitry with Neuromodulation (invasive and non-invasive brain/nervous system stimulation). E.g., Transcranial Magnetic Stimulation (TMS), Deep Brain Stimulation (DBS), Transcranial Direct Current Stimulation (tDCS), etc.

Psychiatry 3.0 is both Therapeutic and Diagnostic.

Therapeutic Applications in Psychiatry 3.0

The left dorsolateral prefrontal cortex - L dlPFC - is functioning sub-optimally or abnormally in nearly every psychiatric disorder. Example:

• It can be hyper-active in conditions like Obsessive Compulsive Disorder (OCD), as it is recruited repeatedly and persistently by overclocked cortical-striatial-thalamic loops.

• Conversely, it is under-active in conditions like Major Depressive Disorder (MDD).

Optimizing this brain region’s activity has consistently improved neurocognitive faculties like Executive Function. Resultantly, the severity of psychiatric symptoms like:

• cognitive fog

• chronic worrying

• impulse dyscontrol

• ruminations

• forgetfulness

can be dampened. Because the dlPFC is connected to many different brain regions across numerous brain networks (E.g., Central Executive Network), the beneficial effects scale to all six Neurocognitive Domains (as defined by the DSM).

L dlPFC activity can be optimized through several non-invasive brain stimulation (NIBS) modalities. TMS and tDCS have been the most extensively researched.

Transcranial Magnetic Stimulation - TMS

Magnetic waves travel transcranially to stimulate neurons.

• High frequency (Hf) stimulation excites neurons ~ neurons fire more frequently.

  • Fast.

  • More active.

• Low frequency (Lf) stimulation inhibits neurons ~ neurons fire less frequently.

  • Slow.

  • Less active.

Magnetic pulses are delivered repeatedly, hence it is referred to as repetitive transcranial magnetic stimulation - rTMS. Administered over the prefrontal cortex (PFC), TMS induces the release of important Neurotransmitters like Dopamine within meso-limbic and meso-striatal neurocircuits. These neurocircuits are implicated in motivation, learning, reward, and conversion of habits into behaviors; but low Dopamine levels contribute to negative psychotic symptoms like a-motivation and anhedonia. Fortunately for patients who were without effective treatments until now, TMS has been efficacious at reversing negative symptoms in psychosis and schizophrenia. Related mechanisms and network level changes also underlie the treatment of depression.

Transcranial Direct Current Stimulation - tDCS

Direct electric current - DC, as opposed to AC - is delivered transcranially. tDCS does not directly trigger the firing of neurons. Instead, it alters the resting membrane potential of pre- and post-synaptic neurons.

Ethereans may intuitively analogize this with the base gas fees required for transactions: the lower the gas fees, cheaper the transaction cost; the more positive the resting membrane potential, the easier for a neuron to fire Action Potentials.

• Cathodal tDCS introduces Inhibitory Post-Synaptic Currents (IPSCs) to hyper-polarizes the resting membrane potential - makes the number more negative - requiring more energy for the neurons to fire.

• Anodal tDCS introduces Excitatory Post-Synaptic Currents (EPSCs) de-polarizes the resting membrane potential - makes the number less negative - requiring less energy for the neurons to fire.

For this reason, the greatest effect sizes generally result when anodal tDCS is administered in conjunction with a cognitive intervention. The prefrontal cortical neurons are easier to recruit for firing; e.g., in combination with meditation (E-Meditation).

Variational modalities like Transcranial Alternating Current Stimulation - tACS, Transcranial Random Noise Current Stimulation - tRNS, TMS sub-modalities like Intermittent Theta-Burst TMS - iTBS, and newer techniques like Transcranial Focused Ultrasound Stimulation (tFUS) or Transcranial Pulse Stimulation (TPS) are all very promising with their individual risk/reward profiles.

By optimizing the activity of the L dlPFC, NIBS nudges the Nervous System’s state towards generalized well-being. From an Active Inference perspective, the system is better able to minimize its free energy (Entropy). It alleviates dis-ease in nearly all conditions including but not limited to: depression, anxiety, PTSD, OCD, schizophrenia, chemical and behavioral addictions, ADHD, autism, fibromyalgia, dementia, multiple sclerosis, Huntington’s disease, Parkinson’s disease, osteoarthritis - essentially, any Nervous System state in which the L dlPFC is functioning sub-optimally.

Transcranial Magnetic Stimulation induces favorable neuro-protective and neuro-plastic changes in the Nervous System.

These benefits emanate throughout the Hierarchy of Life, and even beyond to sub-atomic particles.

Neuromodulation of regions other than the L dlPFC can also be therapeutic.

Diagnostic Applications in Psychiatry 3.0

The Nervous System can be understood as a computer. From a Cybernetic Systems perspective, this system is perpetually processing incoming information through the Ether.

In place of electrons zipping along wires and silicon chips, the Nervous System is powered by electricity and neurotransmitters flowing throughout its distributed neuro-circuitry.

Experience largely governs the equilibrium of excitation and inhibition. As such, the Nervous System is constantly in flux. The balance of Neurotransmitters is continuously shifting.

Glutamate and GABA are the most ubiquitous neurotransmitters, so they primarily govern the state of positive to negative charges. Glutamate is excitatory (de-polarizes a neuron; + ), while GABA is inhibitory (hyper-polarizes a neuron; - ). The Nervous System’s state of excitability is a function of the excitation-inhibition balance - E/I balance.

This balance, among numerous features, is also characterized by a certain economy of transacting Neurotransmitters wherein the chemical messengers come to exhibit the property of Moneyness. E/I balance can be queried through TMS-EMG paired-pulse paradigms:

Electromyography (EMG) is hooked up to a subject, and neuromuscular output is monitored in real time. A TMS machine is introduced to analyze objective biomarkers that correlate with the Nervous System’s state of excitability (E/I balance).

Low excitability states can correlate with negative psychotic symptoms, depression associated psychomotor retardation, neuromuscular blockade with dopaminergic antipsychotics, and so forth. High excitability states can correlate with restlessness, hyper-vigilance, serotonin syndrome spectrum, and so forth.

At last, objective biomarkers for psychiatric disorders are available non-invasively. Until now, the diagnosis of mental health has been dependent on subjective assessments of behavior.

Similarly, Electroencephalography (EEG) data are valuable. There are very reliable biomarkers of important facilities like Executive Function. E.g., Peak Alpha EEG. Waveforms and neuro-signatures correlating with more specific domains can also be gathered. Much like neurofeedback, this can gamified diagnostic and therapeutic aims.

There are more diagnostic modalities as well such as functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and others.

Discussion

While Psychiatry 3.0 can offer a personalized approach to mental health and well-being, it is important to appreciate how it integrates with Psychiatry 1.0 and Psychiatry 2.0. I.e., many foundational principles of Psychiatry 1.0 are consistent with computational and systems neuroscience as they have been described within the framework of Active Inference and Free Energy Principle. E.g., the psychoanalytic concept of Psychic Energy can be contextualized as Free Energy.

Psychiatry 2.0 has been instrumental for enabling the de-institutionalization of patients out into the community. This is so because pharmacotherapy is effective at containing severe agitation, paranoia, psychosis, mania, and states characterized by high risk of harm to self or others. But the benefits end there. Medications can help reverse Disorder, but they do not promote the optimization of Order or higher functioning status. Side effects are countless.

For these reasons and many more, TMS offers an Asymmetric Value Proposition. NIBS categorically adds value to patients’ lives with limited side effects. This must be emphasized because Psychiatry has been reduced to a Behavioral Science, reliant heavily on medications that are expected to function as if x symptoms then y treatment.

Perverse incentive structures and Moral Hazards facilitated by Traditional Contracts cannot be ignored. The value extractive nature of legacy systems leaves patients “holding the bag.” They are left jumping through hoops to deliberately fail medication treatments before they can be “authorized” to receive life-changing treatments like TMS. Rating scales and p-values are not necessary to infer how this might affect a patient with major depression; unironically, depression is one of the most robust clinical indications for TMS. The dispensing of pharmaceuticals benefits only the complex that perpetuates itself.

Are we servicing a need, or fueling one?

Systemically, this has negative impacts on public mental health. In its present form, the healthcare structure is simply not configured to effect the best outcomes for patients. This also contributes to the wide heterogeneity of results in studies assessing the efficacy of NIBS; the feedback loops need to be reconfigured. Fortunately, Smart Contracts can change this by re-establishing Trustlessness. Peer-to-peer agreements amongst patients, physicians, therapists, and all essential community members involved in healthcare encounters, effectively end up replacing the third parties in such Trustless networks.

In Conclusion,

Psychiatry 3.0 can solve important problems for the world. More research is needed for better understanding this technology so that it can be personalized successfully. Distributed Ledger Technology (DLT) can scale Psychiatry 3.0 and democratize access to life-transforming interventions by replacing Traditional Contracts with Smart Contracts. By leveraging DLT to integrate research with mental healthcare, Psychiatry and Science can be decentralized simultaneously. DePsi & DeSci.

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