Indian Journal of Clinical Psychiatry REVIEW ARTICLE

An Official Journal of Association of Clinical Psychiatry doi: 10.54169/ijocp.v3i01.70

(Indian Psychiatric Society- Uttar Pradesh State Branch (IPS-UPSB))

Newer Neuromodulation Techniques for Psychiatric

Disorders: A 2023 Update
Sujita K. Kar1*, Vidya KL2
Department of Psychiatry, King George’s Medical University, Lucknow, Uttar Pradesh, India.
1

Department of Geriatric Mental Health, King George’s Medical University, Lucknow, Uttar Pradesh, India.
2

Abstract
There are several challenges exist in the management of psychiatric disorders. Many
of these factors are related to psycho-social circumstances. Despite being diagnosed
accurately and receiving adequate treatment, several patients with psychiatric dis-
orders remain nonresponsive to treatment, commonly called a state of treatment
resistance. Though pharmacological management and psychotherapy are well-es-
tablished treatment modalities in the management of psychiatric disorders, several
patients show inadequate responses requiring treatments using neuromodulation.
Sometimes, the nature of psychiatric illness also determines the preference of going
for neuromodulation. For example, managing a patient with acute suicidal behavior
or catatonia may be better and rapidly treated with electroconvulsive therapy (ECT).
Recent decade has witnesses several newer spectra of neuromodulation techniques
using a range of stimuli (electrical, magnetic, sonic, photic, thermal, etc) to neuro-
modulation for the management of several neuropsychiatric disorders. This review
ARTICLE INFO highlights the newer neuromodulation techniques and their potential roles in man-
aging psychiatric disorders with research evidence.
*Correspondence:
Sujita K. Kar
[email protected]
Department of Introduction
Psychiatry, King
George’s Medical
University, Lucknow, Conventional neuromodulation techniques for
Uttar Pradesh, India. Psychiatric disorders
Dates: Since the introduction of path-breaking electroconvulsive therapy (ECT), a little
Received: 20-03-2023 short of a century ago, the field of neuromodulation has shown tremendous
Accepted: 18-05-2023 growth and now has been broadly classified into noninvasive and invasive neu-
Published: 30-06-2023 romodulation. A brief update on the advances of conventional neuromodulation
techniques is being given below.1-5
Keywords:
Newer Electroconvulsive therapy (ECT)
neuromodulation,
Psychiatric disorders, Despite the advances in the field of neuromodulation, no other techniques have
Brain stimulation, been able to take the place of ECT, which remains the treatment of choice for
Psychiatry research. life-threatening conditions like catatonia, food refusal and severe depression
with active suicidality till date.6 However, over time, there has been improve-
How to Cite: ments in the technique of ECT in terms of better efficacy and tolerability.
Kar SK, Vidya KL. Newer Direct or unmodified ECT has become part of history with the Mental Health
Neuromodulation
Techniques for
Psychiatric Disorders: © IJOCP, 2023. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-Sha-
A 2023 Update. Indian reAlike 4.0 International (CC BY-NC-SA 4.0) License, which allows users to download and share the article for
non-commercial purposes, so long as the article is reproduced in the whole without changes, and the original
Journal of Clinical authorship is acknowledged. If you remix, transform, or build upon the material, you must distribute your con-
Psychiatry. 2023;3(1): tributions under the same license as the original. If your intended use is not permitted by statutory regulation
13-21. or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit https://creativecommons.org/licenses/by-nc-sa/4.0/
doi: 10.54169/ijocp.v3i01.70
 Newer neuromodulation techniques for management of Psychiatric disorders

care Act introduced in 2017. Newer brief pulse ECT disease and OCD. New noninvasive VNS devices
machines are found to be more efficacious and are being evaluated in stress-related disorders but
ultra-brief pulses cause minimal cognitive deficits conclusive evidence is lacking.16
and are recommended to be selected depending on
the patient’s clinical profile. Further, right unilateral Deep brain stimulation (DBS)
frontal ECT is being recommended again to reduce Deep brain stimulation is a favorable invasive neuro-
cognitive side effects.7 modulation technique, especially when depression
or OCD are treatment resistant and intractable.17
Repetitive transcranial magnetic However, recent recommendations of the neuro-
stimulation (rTMS) modulation society and the Indian Society for Ste-
The stigma surrounding ECT, which infamously is reotactic and functional neurosurgery (ISSFN) must
referred to as shock therapy by public has impelled be followed before implementing the procedure.
the introduction of rTMS in psychiatry. Maximum This group recommendation has specified three
evidence for the use of rTMS has been for treat- conditions: treatment-refractory depression, OCD
ment-resistant depression as adjunctive treatment and Tourette syndrome.18
8
. Additionally, it is also indicated in migraine pro-
phylaxis9. Intermittent Theta burst stimulation (iTBS) Newer neuromodulation
which has been approved for use in depressive techniques for Psychiatric disorders
disorders, has the advantage of reduced duration of Over the past decade various neuromodulation
individual sessions and is cost-effective 10. Recently techniques have been used for the treatment of psy-
deep TMS has been introduced and is indicated as chiatric disorders. The commonly used conventional
adjunctive treatment in treatment-resistant obses- neuromodulation techniques cannot completely
sive-compulsive disorder (OCD). Deep TMS has the manage the psychiatric disorders; hence, there is
advantage of penetrating the deeper structures of a perceived need to find a cost-effective, safe and
brain, overcoming the shortcomings of the conven- highly efficacious neuromodulation facility that will
tional rTMS. Further deep TMS is indicated in tobacco enhance the outcome of care in psychiatric disor-
anti-craving as well as anxiety comorbid with major ders. The newer neuromodulation techniques with
depressive disorder (MDD) 11. relevance to psychiatric disorder management are
discussed here.
Transcranial direct current
stimulation (tDCS) Transcranial alternating current
One of the barriers to accepting ECT or rTMS has stimulation (tACS)
been the need for repetitive sessions delivered only Transcranial alternating current stimulation (tACS)
in institutional set ups. tDCS has given the hope is a form of transcranial electrical stimulation (tES)
and direction for a domiciliary approach to neuro- that uses low-intensity alternating electric current
modulation 12r. Being a portable device, tDCS has on the scalp to modulate the neuronal activity of
maximum evidence in the treatment of depressive the underlying cortex.19 The pathological oscillatory
disorders, followed by treatment-resistant cases of activity of the neurons are reported in psychiatric
schizophrenia and OCD 13. Research is underway for disorders. tACS alters the membrane potential of the
it’s use in cognitive disorders.14 neurons by modulating the oscillatory frequency of
the neurons, bringing them to the frequency of the
Vagal nerve stimulation
induced electric current. 20 Accumulating evidence
Vagal nerve stimulation(VNS) is a promising add on suggests that 20:
invasive and approved neuromodulation strategy • tACS at alpha frequency over the dorsolateral
in treatment of refractory depression 15. Preliminary prefrontal cortex improves depression.
data on efficacy has also been reported in other psy- • tACS at gamma frequency improves memory in
chiatric conditions like schizophrenia, Alzheimer’s patients with Alzheimer’s disease.

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 Newer neuromodulation techniques for management of Psychiatric disorders

Evidence suggest that tACS is more beneficial than on reaching the cortical surface, it gets converted
tDCS in causing cognitive improvement. 20 tACS has to an electrical stimulus and produces focal neu-
been used in the treatment of depression, schizo- romodulation. However, the major limitation with
phrenia, and cognitive impairments in Alzheimer’s TMS being the device is large and capable of doing
disease. 20 Even in healthy individuals, tACS was superficial cortical neuromodulation (due to limited
found to improve cognition. 20 In elderly individuals, permeability). Recently, researchers are working on
tDCS improves associative memory performance. 21 implanting micro-magnet in the targeted neuronal
As per the existing evidence, there is no serious or tissue to do neuromodulation. 28 Evidence suggests
long-term side effects and further safety investiga- that the spatial orientation of the micro-TMS coil
tions are required. with respect to the neurons is largely responsible
for producing a variety of neural responses. 28 The
Transcranial random noise micro-TMS is in early stage of development and
stimulation (tRNS) holds promise for precise person-centered neuro-
Transcranial random noise stimulation (tRNS) is a modulation for various neuropsychiatric disorders.29
newer neuromodulation technique. Here, low-volt-
age electric current passes through the brain at Magnetic seizure therapy
random frequencies. 22 The frequency band used Magnetic seizure therapy (MST) uses high-frequency
in tRNS ranges between 0.1 Hz to 640 Hz. Frequen- magnetic stimulus to produce convulsion, which has
cies between 0.1Hz to 100Hz are low-frequency, a similar mechanism like ECT. 30 MST also requires
whereas frequency between 100 to 640 Hz is called
general anesthesia and skeletal muscle relaxant
high-frequency. 22,23 The effects of tRNS often last
for carrying out the procedure. The cognitive side
for an hour following application for 10 minutes 23.
Though evidence suggests that high-frequency effects produced by MST is significantly lower than
tRNS produces neuronal excitability more effectively, ECT 30. MST using various frequencies of magnetic
the therapeutic efficacy depends on the width of the pulses were tried in research for the treatment of
selected frequency.22 Research supports that when a major depressive episode, and it was found that
frequency with 100–700Hz is given, it produces more patients receiving high-frequency MST (100Hz), had
cortical excitability than a frequency of 100-400Hz highest remission rate. 31 In another interesting study,
and 400–700Hz given.22 Longer application of tRNS, it was found that MST effectively reduces suicidal
either through a single prolonged administration or behavior (remission rate from suicide by approxi-
multiple short applications, is known to enhance mately 48%) and this effect was elicited 32. Low to
neuroplasticity. 24 moderate-frequency MST is associated with higher
tRNS produces more intense cortical excitability
reduction of suicidality compared to those receiving
than tDCS. 25 High-frequency tRNS has been used in
high-frequency. 32 MST is also found to be as effective
various research and found to enhance visual atten-
as ECT in reducing the symptom severity of schizo-
tion, facial perception, facial emotion recognition,
arithmetic skills & calculation, pain modulation, phrenia 33. MST has minimal neurocognitive sequel.
mood regulation (effective in depression), improving Patients receiving MST, often have intact memory
the negative symptoms of schizophrenia, reducing functioning and their reorientation is achieved early
tinnitus and cognitive enhancement. 22,26 A random- following the procedure. 34
ized controlled trial that evaluated the role of tRNS
in the management of depression found that tRNS Optogenetics
is not superior to its sham counterpart in the treat- Optogenetics is a newer intervention modality that
ment of depression. 27 uses optical and genetic methods to manipulate the
cell level for behavioral modification. 35,36 The preci-
Micro transcranial magnetic
sion of intervention in optogenetics goes to cell and
stimulation
genetic level. 37 The photosensitive neurons of the
Transcranial magnetic stimulation (TMS) uses brain and retina are often the targets in optogenetic
magnetic stimulation, which is applied to scalp and intervention. Photic (optic) stimuli produce several

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 Newer neuromodulation techniques for management of Psychiatric disorders

changes in these neurons, subsequently altering the nerve stimulation is a safe technique and has been
functional connectivity by modulating sleep, arousal, successfully used in managing refractory (drug-re-
behavior, mood regulation, reward processing, sistant) epilepsy50,52, depression46 , and migraine.49
and fear. 37 There are possible roles of optogenetic Adverse effects of transcutaneous vagus nerve
interventions in schizophrenia, depression, anxiety stimulation are often mild to moderate and may be
disorders and substance use disorder. 37,38 manifested as erythema & pain at the stimulation
site, headache, nausea, vertigo, fatigue. 50–52
Photobiomodulation
Transcranial Photobiomodulation more often uses
Transcutaneous electrical cranial-
near-infrared (NIR) light, which easily penetrates the auricular acupoint stimulation
head and reach the brain surface. 39 The therapeutic (TECAS)
effect of this procedure is mediated by mitochondrial Transcutaneous electrical cranial-auricular acupoint
cytochrome C oxidase activation, though heat-gated stimulation (TECAS) is a noninvasive electrical
ion channels also play a role. 39 Increased cerebral nerve stimulation recently introduced in managing
blood flow, and reduction of the inflammatory
depression. 53,54 TECAS enhances the connectivity
process facilitate neuronal repair and neuroprotec-
between the default mode network (DMN), and
tion after Photobiomodulation. 39 There is a possible
right frontoparietal network (RFPN). It also increases
role of Photobiomodulation in the management of
the connectivity between default mode network
stress, depression, anxiety, and neurocognitive dis-
(DMN), and dorsal attention network (DAN), which
orders. 39-42 Photobiomodulation reduces oxidative
is responsible for its therapeutic effects. 53
stress by reducing the production of reactive oxygen
species and facilitating neuroplasticity.41 Ceranoglu Ultrasound-mediated noninvasive
et al., (2022) has used Photobiomodulation in the brain stimulation
treatment of autism spectrum disorder and found
that there is a noticeable improvement in the core Transcranial ultrasound Ultrasound-based noninva-
symptoms of autism following the intervention.43 sive brain stimulation (NIBS) is an innovative tech-
nique that shows promise for treating psychiatric
Trigeminal nerve stimulation disorders. It utilizes ultrasound waves to deliver
Trigeminal nerve stimulation is a noninvasive neuro- precise stimulation to specific regions of the brain
without requiring surgery. 55,56 Compared to tradi-
modulation technique that stimulates the peripheral
tional methods like deep brain stimulation (DBS),
cutaneous endings of the trigeminal nerve on the
ultrasound-based NIBS has the potential to be safer
scalp, there by modulating the associated brain
and more effective.
areas linked to trigeminal nerve nucleus.44–46 Tri-
Research has demonstrated the effectiveness of
geminal nerve stimulation is safe, with no major side
ultrasound-based NIBS in addressing various psy-
effects.46 Existing evidence supports the potential
chiatric disorders, 57,58 including depression, anxiety,
role of trigeminal nerve stimulation in managing
and obsessive-compulsive disorder (OCD). A recent
major depressive disorder, posttraumatic stress
study revealed that ultrasound-based NIBS is equally
disorder, attention-deficit hyperactivity disorder
effective as medication in treating depression, while
(ADHD) and epilepsy.44–48
causing fewer side effects. Furthermore, NIBS is
Transcutaneous vagus nerve being explored as a potential treatment option for
schizophrenia and bipolar disorder.
stimulation
Although still in its early stages of development,
Transcutaneous vagus nerve stimulation is a newer ultrasound-based NIBS could potentially transform
noninvasive neuromodulation technique that the treatment landscape for psychiatric disor-
stimulates the auricular branch of vagus through ders. Further investigation could establish ultra-
electrode placement by modulating the activity of sound-based NIBS as a safe and effective approach,
associated brain areas.48–51 Transcutaneous vagus significantly improving the lives of millions affected

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 Newer neuromodulation techniques for management of Psychiatric disorders

Table 1: Newer neuromodulation techniques and current status of evidence

Modality of neuromodulation Target conditions Evidence

Transcranial alternate current • Depressive disorders Promising results from small

stimulation (tACS) • Chronic insomnia RCTs 68,69
• Cognitive impairment
• Schizophrenia
Transcranial random noise • Mood regulation Small RCTs with conflicting
stimulation (tRNS) • Depressive disorders results 70,27
• Negative symptoms of schizophrenia
• Cognitive impairment Preliminary case studies

Micro transcranial magnetic Ultra-focal brain stimulation Ongoing studies in healthy

stimulation volunteers29
Magnetic seizure therapy • Major depressive episode Positive findings from Systematic
• Suicidal behaviour reviews of RCTs 71
• Schizophrenia
Optogenetic stimulation • Possible roles of optogenetic Preclinical studies in animal
interventions in schizophrenia, models 37,38
depression, anxiety disorders and
substance use disorder
Transcranial Photobiomodulation • Autism spectrum disorder Positive findings from proof of
• Possible role in management of stress, concept studies 43
depression, anxiety, neurocognitive
disorders
Trigeminal nerve stimulation • Major depressive disorder Small Randomized control trials 72
• Attention deficit hyperkinetic disorder
• Posttraumatic stress disorder
• Epilepsy
Transcutaneous vagal nerve • Refractory epilepsy, depression and Promising Results from open-
stimulation migraine label trials 73
Transcutaneous electrical cranial- • Mild to moderate depression Positive findings from
auricular acupoint stimulation multicentric RCT 54
(TECAS)
Transcranial Ultrasound-based • Putative role in depression, anxiety and Animal Studies and studies on
noninvasive brain stimulation (NIBS) Obsessive-compulsive disorders healthy human volunteers 74

by these conditions. 58,59 Here are some of the advan- • Further research is necessary to ascertain
tages associated with ultrasound-based noninvasive ultrasound-based NIBS’s long-term safety and
brain stimulation for psychiatric disorders: efficacy.
• Enhanced safety and effectiveness compared to • NIBS devices and adequately trained personnel
traditional brain stimulation methods. are unavailable due to its recent introduction.
• Ability to target specific brain regions for treat- • The cost of ultrasound-based NIBS might be
ment. prohibitive for some individuals.
• Applicability in treating a range of psychiatric Despite these obstacles, ultrasound-based nonin-
disorders. vasive brain stimulation represents an encouraging
• Potential to significantly improve the lives of new technology that could revolutionize psychiatric
many individuals. disorder treatment. 57 Continued research and devel-
However, several challenges must be addressed opment could establish ultrasound-based NIBS as
before ultrasound-based noninvasive brain stimu- a safe and effective approach, offering significant
lation can be widely implemented as a treatment improvements to the lives of millions affected by
for psychiatric disorders:55 these conditions.

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 Newer neuromodulation techniques for management of Psychiatric disorders

Future directions ing and designing musical stimuli, it is possible

to elicit specific emotional and cognitive
While several established forms of neuromodula- responses, leading to changes in brain activity
tion, such as electrical and magnetic stimulation, and behavior.66,67
ongoing research and development efforts are It’s important to note that while these newer forms
exploring other modalities, here are some newer of neuromodulation show promise, many of them
forms of neuromodulation: are still in the experimental or research stages.
• Thermal Neuromodulation: Thermal neuromod- The field of neuromodulation is rapidly evolving,
ulation involves using temperature changes to and ongoing studies are necessary to fully under-
modulate neural activity. It can be achieved stand their mechanisms of action, efficacy, and
through techniques like transcranial cooling safety before they can be widely adopted in clinical
or heating. These temperature alterations can practice. Table 1 below summarizes the evidence
influence brain function and have potential base of newer neuromodulation techniques.
applications in pain management, psychiatric
disorders, and neurorehabilitation. However,
research in this area is still in its early stages, and
Conclusion
further studies are needed to explore its efficacy In the past decade, there have been notable
and safety.60,61 advancements in neuromodulation techniques, pro-
• Chemical Neuromodulation: Chemical neuro- viding new and improved possibilities for patients
modulation involves the use of chemical agents struggling with various mental health disorders.
to modulate neural activity.62 It can be achieved Although these emerging techniques show great
by delivering neurotransmitters, neuromodula- potential, conducting ongoing research, rigorous
tors, or pharmacological agents to specific brain clinical trials, and long-term follow-up studies is
regions. Chemical neuromodulation techniques important to establish their safety, effectiveness,
hold promise in treating various neurological and and optimal usage. Moreover, ethical concerns and
psychiatric disorders, but their development is criteria for patient selection need to be carefully
still ongoing, and rigorous testing is required to addressed to ensure responsible and fair utilization
ensure their effectiveness and safety.62,63 of these interventions.
• Audio-Visual Entrainment (AVE): Audio-visual To summarize, as of 2023, the field of neuromod-
entrainment involves the presentation of syn- ulation for psychiatric disorders has made signifi-
chronized audio and visual stimuli, typically cant progress. Deep brain stimulation, transcranial
through specialized devices like light and sound magnetic stimulation, vagus nerve stimulation, and
machines or goggles. The purpose is to induce closed-loop systems have all seen advancements,
specific brainwave patterns and promote desired offering hope for better treatment outcomes,
states of consciousness, such as relaxation or symptom management, and improved quality
focus 64,65. AVE is often used in meditation, stress of life for individuals with psychiatric conditions.
reduction, and cognitive enhancement prac- As research and innovation continue, it is crucial
tices. While it may have some beneficial effects, to strike a balance between progress, safety, and
more research is needed to fully understand its ethical considerations to ensure the responsible
implementation of these state-of-the-art therapies
mechanisms and effectiveness.
in clinical practice.
• Music Neuromodulation: Music has been found
to profoundly impact the brain and can be
considered a form of neuromodulation. The Author’s contribution
therapeutic use of music, known as music 1st Author: Conceptualization, literature search, man-
therapy, has shown potential in various clinical uscript writing, manuscript editing
settings, including pain management, mood 2nd Author: Literature search, manuscript writing,
disorders, and rehabilitation. By carefully select- manuscript editing.

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 Newer neuromodulation techniques for management of Psychiatric disorders

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