# Psychiatry 3.0

By [Bhau](https://paragraph.com/@bhau) · 2022-11-21

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Highlights:
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*   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…](https://www.statnews.com/2022/01/12/brain-stimulation-jolting-brain-circuits-with-electricity-moving-from-radical-to-almost-mainstream/)”

![](https://storage.googleapis.com/papyrus_images/1ab9e74a8ea5760b776d57de703a20265d1e6b3046fb22a6c461d4e6692da974.png)

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
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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)._
    

![](https://storage.googleapis.com/papyrus_images/7bc2dbddf94226dfc4940f6ad682f6274d19839aaffd205ab04ebc15c2fcf14d.png)

Optimizing this brain region’s activity has [consistently](https://pubmed.ncbi.nlm.nih.gov/?term=tms+cognition&filter=pubt.meta-analysis) 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](https://www.researchgate.net/publication/266325299_Classifying_neurocognitive_disorders_The_DSM-5_approach/figures?lo=1)).

![](https://storage.googleapis.com/papyrus_images/3583132c796702d1feb2b67cfcc15fe91bd1faae69986353a179e19678ce6fc9.png)

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.

![](https://storage.googleapis.com/papyrus_images/9f4b4a749975c3e0c8516efa1c3140939799b40ca8e6913cc7a13cf4ba0a5c6a.gif)

*   **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](https://pubmed.ncbi.nlm.nih.gov/12213264/) 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**](https://pubmed.ncbi.nlm.nih.gov/29471017/). Related mechanisms and network level changes also underlie the [treatment of depression](https://paradigm-psychiatry.com/communityblog/how-does-tms-relieve-depression).\*

![](https://storage.googleapis.com/papyrus_images/eb798ddf405bee4af53822363d9b9b854a5be58036aa7943c2117e539fc90230.png)

### 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._

![](https://storage.googleapis.com/papyrus_images/d243be801143923d66c1bef4e87f0c291d00cd6bdaf17e12b7e30395bdcce987.png)

*   **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)_](https://www.brainstimjrnl.com/article/S1935-861X\(16\)30267-4/fulltext)_._

![tDCS is typically administered for 20 minutes with a dosing intensity of 1 or 2 milli-amperes (mA). Image Credit: https://www.brainlatam.com/blog/novel-imaging-markers-of-current-flow-in-transcranial-direct-current-stimulation-tdcs-1533](https://storage.googleapis.com/papyrus_images/0d1038a4177fbb00433ac1f45d16cb3d0e259b50872506e2e415bad0e4f6ab78.png)

tDCS is typically administered for 20 minutes with a dosing intensity of 1 or 2 milli-amperes (mA). Image Credit: https://www.brainlatam.com/blog/novel-imaging-markers-of-current-flow-in-transcranial-direct-current-stimulation-tdcs-1533

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**](https://www.frontiersin.org/articles/10.3389/fneur.2019.00549/full)) or Transcranial Pulse Stimulation ([**TPS**](https://pubmed.ncbi.nlm.nih.gov/?term=transcranial%20pulse%20stimulation%20tps)) are all very promising with their individual risk/reward profiles.

![tDCS, tRNS, and tACS waveforms](https://storage.googleapis.com/papyrus_images/8e960f7966328d1c7d757024a5df9e7d13552dca1b23ef1053a7750956a16e58.png)

tDCS, tRNS, and tACS waveforms

By optimizing the activity of the L dlPFC, NIBS **_nudges_** the Nervous System’s [state](https://ethereum.org/en/developers/docs/evm/#from-ledger-to-state-machine) towards **generalized well-being**. From an [**Active Inference**](https://www.youtube.com/watch?v=yWsURAZ8vSo) 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_**.

![](https://storage.googleapis.com/papyrus_images/dad15f96c9dba2d0766fddbbbba9c2930ec18c6e7211b2543f82f50b67a5106e.png)

Transcranial Magnetic Stimulation induces [favorable neuro-protective and neuro-plastic changes](https://www.frontiersin.org/articles/10.3389/fnhum.2015.00303/full) in the Nervous System.

![](https://storage.googleapis.com/papyrus_images/753f72d3c9a9bdd2e5ec1e7f144c83badd90422c542a1b63876e58fb4728cfab.png)

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

![](https://storage.googleapis.com/papyrus_images/74d676c456a50e48e478c1c537277ba994377cb266d229a630dd3c3ce3060998.png)

Neuromodulation of regions [other than the L dlPFC](https://pubmed.ncbi.nlm.nih.gov/36281767/) 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](https://mirror.xyz/bhau.eth/EzPUC8pX8wSsYd8OtEKu4Hd_u-UXk0HBui5vSvcZHlU).

![Generative Processes that build Models of the World are operational mandates for living systems in the framework of Active Inference and Free Energy Principle. Cybernetic Systems are configured to reverse Entropy (Variational Free Energy).](https://storage.googleapis.com/papyrus_images/b99a66ea08e016579e8955ef20b9035d72d237b9d29a99dda37cba2cb6279ece.png)

Generative Processes that build Models of the World are operational mandates for living systems in the framework of Active Inference and Free Energy Principle. Cybernetic Systems are configured to reverse Entropy (Variational Free Energy).

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.

![Active Inference entails minimizing Surprise, or Prediction Errors, about the future.](https://storage.googleapis.com/papyrus_images/8a51a1eb59631faa5c90d8c3ed6c1e7861e4a83eb8469dcbe0b9de6658c7da27.png)

Active Inference entails minimizing Surprise, or Prediction Errors, about the future.

[Experience](https://pubmed.ncbi.nlm.nih.gov/27238867/) largely governs the **_equilibrium_** of excitation and inhibition. As such, the Nervous System is constantly in **flux**. The balance of Neurotransmitters is continuously shifting.

![Relative proportions of Neurotransmitters in the Nervous System. Glutamate is the most prevalent, conceivably in order to sustain an excitable state ready for Action. Source.](https://storage.googleapis.com/papyrus_images/e92fe02d759661747ac013cf41e3f9e654a4cbfb3a470d27c5a2e7d2c94b4745.png)

Relative proportions of Neurotransmitters in the Nervous System. Glutamate is the most prevalent, conceivably in order to sustain an excitable state ready for Action. Source.

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**](https://pubmed.ncbi.nlm.nih.gov/27238867/).

![](https://storage.googleapis.com/papyrus_images/4c79458215e402d751e05e4715d51ddc55148180ad2af56bc49f1130d1150264.png)

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](https://bhau.substack.com/p/moneyness-of-eth-and-neurotransmitters). **E/I balance** can be queried through **TMS-EMG** **_paired-pulse paradigms_**:

![](https://storage.googleapis.com/papyrus_images/c8496e59d78b87c7104b90b05d6a2b4936557a03be3c69b008900268b470e038.png)

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**).

![Short interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) are two methods to gauge the Nervous System's state of excitability. Other probes like Cortical Silent Period (CSP) and Long Interval Intracortical Inhibition (LICI) are also valuable.](https://storage.googleapis.com/papyrus_images/ff6e03073dc4bfcad6f4994ed0df505d3e72218466a2af32c3c93f51b66ed985.png)

Short interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) are two methods to gauge the Nervous System's state of excitability. Other probes like Cortical Silent Period (CSP) and Long Interval Intracortical Inhibition (LICI) are also valuable.

**_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.

![](https://storage.googleapis.com/papyrus_images/ecb5d4e91cc2e9081a72c67cb29b0ea3c0443c68e0e71f8bc7bb390d02911dee.png)

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**.

![A Systematic Review of TMS and neurophysiological biometrics in patients with Schizophrenia - https://pubmed.ncbi.nlm.nih.gov/34933940/](https://storage.googleapis.com/papyrus_images/fab721c51710000f8613d6273f04acc6b8c302b5e234792d33dd334264e8a31e.png)

A Systematic Review of TMS and neurophysiological biometrics in patients with Schizophrenia - https://pubmed.ncbi.nlm.nih.gov/34933940/

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.

![](https://storage.googleapis.com/papyrus_images/2c8719d135fccfa937a0e694c89cd89834429585e1b4928616aa008c099020aa.png)

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

Discussion
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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_](https://www.frontiersin.org/articles/10.3389/fnhum.2022.929940/full).

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.

![](https://storage.googleapis.com/papyrus_images/9631774bf550e89f0c35c0a6679860063d24e9fea789a03e1a9230cc15d07934.png)

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_.

![TMS and NIBS side effects are minor and self-limited.](https://storage.googleapis.com/papyrus_images/4262751fa483106a3ecbc63f738836aa5a4b9aa84ca4d1573b19b493c56853fd.png)

TMS and NIBS side effects are minor and self-limited.

Perverse incentive structures and [Moral Hazards facilitated by Traditional Contracts](https://bhau.substack.com/p/traditional-contracts-and-the-violation) 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](https://substack.com/inbox/post/84319782). 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.

![Smart Contracts imbue networks with Trustlessness. Trustless networks can verify events in peer-to-peer manner without 3rd parties. With Smart Contracts, healthcare encounters can be trustlessly verified through "consensus algorithms" like Proof-of-Stimulation.](https://storage.googleapis.com/papyrus_images/d0e14a8bc319392da314916ec8513192dd3072560a620eb5d1477993e320f6f8.png)

Smart Contracts imbue networks with Trustlessness. Trustless networks can verify events in peer-to-peer manner without 3rd parties. With Smart Contracts, healthcare encounters can be trustlessly verified through "consensus algorithms" like Proof-of-Stimulation.

In Conclusion,
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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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*Originally published on [Bhau](https://paragraph.com/@bhau/psychiatry-3-0)*