brain stimulation techniques (rTMS, tDCS, DBS)

BRAIN
STIMULATION
TECHNIQUES
Guided by:
Dr. Abhay Paliwal
Associate professor
Department of
psychiatry
Presented by:
Dr. Mahendra Singh Bhadoriya
PG 3rd year
Department of psychiatry

Topics covered in part 1
• Introduction
• History
• Indications
• ECT stimulus
• Mechanism of action
• Treatment course
• Interactions of medications
• Adverse effects
• ECT in pregnancy
• VNS
• VNS vs ECT
• Pros and cons of VNS

Types of Brain Stimulation
Techniques

To be discussed..
 TMS
 tDCS
 Deep brain stimulation (DBS)

(Transcranial Magnetic
Stimulation)
TMS

History of TMS
1800
1830
1985
1999-
2000
Scientists first
discovered that our
nerve cells carry
electrical activity
The first modern
rTMS device was
developed by
Anthony Barker in
Sheffield, England
Michael Faraday
discovered that a changing
magnetic field can
generate an electric current
(known as magnetic
induction)
Used to study the function
of different brain areas and
causes of neurological and
psychiatric illness and as a
therapeutic tool

History of TMS
2003
2008
2015
2020
Canada approved
the use of rTMS
therapy for
depression
NICE in the UK
approved the
use of rTMS for
treatment
resistant
depression
The FDA in the United
States gave its approval for
rTMS to be used for
treatment resistant
depression
the FDA approved rTMS
treatment for OCD in the
United States

Mechanism of action
Faraday’s law

Terminologies
Stimulus strength A measure of magnetic field, expressed
in terms of percentage of maximum
machine capacity (about 1-3 T)
Motor threshold (MT) Minimum stimulus strength that
produces 5 motor responses out of 10
stimuli when applied over a specified
muscle area
Single pulse Single stimulus given after fixed interval,
for example, after every 5 s
Pulse train Several pulses administered
continuously in a given period of time
Inter-train interval The time gap between two trains
Frequency The number of stimuli in a given pulse

Planning rTMS treatment
 Screening for contra indications
 Determine the area of stimulation
 Localisation of target
 Types of coil to be used

Screening for contraindications
 Metallic hardware in
close vicinity to the coil
 cochlear implants
 Internal Pulse
Generator
 anything that can be
influenced by a
magnetic field
 High risk of seizures
 h/o epilepsy
 CNS lesions
 alcohol withdrawal state
 drugs lowering seizure
threshold
 sleep deprivation.
 family history of
seizures
Absolute contraindication: Relative contraindication:

Areas of stimulation
 Volume stimulated during rTMS: 2cm depth with traditional figure-8
coils
 Cortical surface area stimulated- 3 cm2
 Accessible cortical regions
 Dorsolateral prefrontal cortex
 Supplementary motor area
 Superior frontal gyrus
 Temporo-parietal junction
 Motor cortex
 Occipital cortex
 cerebellum

Localisation of target site
 2 ways of determining the surface landmark of DLPFC:
 5 cm technique :
(MT- Minimum stimulus strength that produces 5 motor responses out of
10 stimuli when applied over a specified muscle area e.g., thumb area)
 Neuronavigational method: employs MRI scan to pinpoint DLPFC with
live video navigation.

Depth of stimulation
 Varies from 2 to 4 cm below the cortical
surface
 only superficial brain structures can be
stimulated.
 depends on:
 type of coil
 intensity of stimulus
 Shape and diameter of coil influences
 Focality
 depth of penetration
 stimulus dose strength

Types of coil
Single TMS
coil
(Circular coil)
• Original coil
used in TMS
Double TMS coil
(Figure of 8 coil)
• Provides a more focal
pattern of activation in
the brain
• 0.7cm subdural depth
• Indicated in MDD
Double cone
coil
• Conforms
more to the
shape of
head

Types of coil
H1 coil
• 1.8cm subdural depth
• Stimulates the bilateral
prefrontal cortex with
preference to the left
DLPFC
• Approved by the FDA in
January 2013 for the
treatment of major
depressive disorder
H7 coil
• 3cm subdural depth
• Stimulates the medial
prefrontal cortex and
anterior cingulate
cortex
• Approved by the FDA
in August 2018 for the
treatment of
obsessive-compulsive
H4 coil
• 1.5cm subdural
depth
• Target the bilateral
insula and PFC
• Cleared by the
FDA for the
treatment of
smoking addiction

Types of
TMS
Singl
e
pulse
TMS
Paired
pulse
TMS
Theta burst
stimulation
Repetitive
TMS
one pulse
at a time
without
regular
rhythm
and at low
rates of
delivery
Pairs of
pulses
separate
d by a
variable
interval
when repeated
at regular
rhythmic
intervals that
usually range
from 1 to 25
Hz
High
frequency
bursts applied
at a regular
frequency
Low
frequenc
y rTMS
(<1Hz):
inhibitory
effect
High
frequenc
y rTMS
(5-20Hz):
excitator
y effect
cTBS:
given
continuousl
y, induces
inhibitory
effect
iTBS:
given
intermitte
ntly,
induces
excitatory
effect

Effects of TMS
 Neuroplasticity
 Depending on frequency of
stimulation can cause
 Long-term potentiation at high
frequency
 Long-term depression at low
frequency
 Alteration in levels of
neurotrophic factors such as
BDNF
 modulation of cortical excitability
and functional connectivity
among brain circuits
Acute effects Prolonged effects
 Phasic activation of neural
circuits
 Observable motor responses (eg
twitch)
 Temporary disruption (eg speech
arrest) or facilitation of ongoing
processing

Applications of TMS
 Diagnostic
 Therapeutic

Diagnostic application
 Used clinically to:
 measure activity of certain brain circuits
 Survey the damage done to particular muscles
following stroke, multiple sclerosis, motor neuron
disease and other injuries or disorders
 Locate tumors and others lesions
 FDA approval is only the navigational stimulation
system for pre surgical planning in patients
undergoing brain surgery

Therapeutic application
 The therapeutic potentials for rTMS have been demonstrated for the
following:
 Treatment-resistant depression
 Obsessive-compulsive disorder
 Posttraumatic stress disorder
 Tourette disorder
 Chronic pain syndrome
 Generalized anxiety disorder (GAD)
 Bipolar disorder
 Movement disorders such as Parkinson disease, functional
tremors, focal epilepsy, cortical myoclonus, spasticity.

 rTMS in depression
 Two major categories of rTMS have been used in most of the studies:
High frequency to the left prefrontal cortex (PFC) and low
frequency to the right PFC.
 Both strategies are found to have similar antidepressant effect, while
low-frequency rTMS of right PFC is better tolerated with lower risk
of seizure.
 Positive predictors of antidepressant response include-
 patients who are younger,
 non-psychotic,
 with shorter duration of depressive episode,
 low level of treatment resistance and
 history of previous response to electroconvulsive therapy (ECT) and/or rTMS.

 rTMS in mania
 Significantly more improvement was observed with right prefrontal
rTMS as compared with left side
 rTMS in schizophrenia
 In schizophrenia, hypoactivity of prefrontal cortex plays a role in the
pathophysiology of negative symptoms,for which high-frequency
rTMS of prefrontal cortex has been used
 for positive symptoms such as hallucinations, which are associated
with hyperactivity of temporoparietal areas, low-frequency rTMS has
been studied.

 rTMS in obsessive compulsive disorder
 Studies evaluating the therapeutic efficacy of rTMS in OCD are limited
 there was significant reduction in secondary depression
 rTMS for craving in substance dependence
 Studies have also revealed the potential anticraving effects of rTMS
in substance dependence.
 In a recent outpatient randomized, double-blind, sham-controlled study,
there was significant reduction in cigarette consumption, as evaluated
objectively by measuring nicotine levels in urine samples and
subjectively by participants’ self-reports; furthermore, the treatment
blocked the craving induced by presentation of smoking cues.

 rTMS in other anxiety disorder
 In an open case series, three patients with treatment-resistant panic
disorder showed modest improvement with 10 rTMS sessions (1 Hz,
110% of MT, 30 trains of 60 s duration) to the right PFC
 In a placebo controlled study, chronic treatment-refractory PTSD, active
rTMS resulted in significant improvement in hyperarousal symptoms
 rTMS in other neuropsychiatric disorders
 Various studies have demonstrated the efficacy of low-frequency rTMS
(0.33–1 Hz) in treating epilepsy and other manifestations of cortical
hyperirritability
 The therapeutic effect of rTMS has been suggested in Parkinson's
disease and in other movement disorders.

rTMS in special population
 Children and adolescents
 There are case reports of improvement with rTMS in bipolar disorder,
unipolar depression, schizophrenia and seizure disorders such as
progressive myoclonic epilepsy.
 There is a need to initially evaluate the safety of rTMS in the child and
adolescent population before studying it for therapeutic applications.
 Geriatric population
 High-frequency stimulation to the left and right dorsolateral
prefrontal cortex (DLPFC) has been found to improve accuracy in
action naming in Alzheimer's disease
 It has also been found to be useful in late-onset depression, post-stroke
depression and depression in Parkinson's disease

Side effects of rTMS
 Transient headache is the most common adverse
effect of rTMS
 Seizures
 Maniac switch
 Delusions
 Unexplained crying and laughter
 Local pain and scalp burns from surface EEG
electrodes
 Histotoxicity due to mass hyperexcitation of
cortical neurons
 Immunological effects by producing changes in
the CD8+ lymphocyte subset

rTMS protocol
Diagnosis Coil
position
Frequency Intensity Pulse No of
sessions
Depression Left DLPFC 10-20Hz 80-110% MT 800-3000 10-30
Schizophreni
a- persistent
auditory
hallucination
s
Left
temporopari
etal
1Hz 80-90% MT 480-1000 5-15
Schizophreni
a- negative
symptoms
Left DLPFC 10-20Hz 110% MT 800-1500 10-15

Current status in treatment
algorithms
 2010- APA included TMS within their practice guidelines
for the treatment of patients with MDD
 Recommends TMS as an initial treatment modality in
the acute phase of depression
 2 devices approved by FDA:
 Neurostar TMS by Neuronetics inc.
 Brainsway deep TMS device

Neurostar TMS by Neuronetics
inc.
 Approved in 2008
 Indication – for the treatment
of MDD in adult patients were
failed to achieve satisfactory
improvement from one prior
antidepressant medication at
or above the minimal effective
dose and duration in the
current episode.
 delivers 10 Hz frequency,
 pulses for trains of four second
duration
 inter train interval of 26
seconds
 session duration of 37.5
minutes total of five daily
sessions of 3000 pulses for six
weeks

Brainsway deep TMS device
 Approved in 2013
 Uses H coil that excites or inhibits
neurons deeper inside the brain
 Indication for the treatment of
depressive episodes. In adult patients,
suffering from MDD who failed to
achieve satisfactory improvement from
previous antidepressant medication
treatment in the current episode.
 Delivers pulses with
 18 Hz frequency for two seconds
 within inter train interval of 20 seconds
 total train duration of 20.2 minutes five
daily session of 1980 pulses for four
weeks
 Optional, another 12 weeks of biweekly
maintenance treatment

(Transcranial Direct Current
Stimulation)
tDCS

Introduction
 Non-invasive, non-convulsive
 A very weak 0.5 to 2 mA direct
electrical current is applied
using at least two surface scalp
electrodes
 Unlike other forms of electrical
stimulation, it does not act by
depolarisation of neuronal
membrane, but by polarity
dependent alteration in RMP
 These effect can last up to 1
hour after stimulation and are
thought to induce neuronal
plasticity
 Portable device operated by 9V
DC batteries

History
Ancient civilizations
applied the electric
torpedo fish to the head to
treat illness
Giovanni Aldini in
1803 used voltaic
devices to stimulate
patients and corpses
(Aldini 1803)
Rudolph Arndt in
1870 applied
electrotherapy to
the scalp to treat
mental illness

History
"Electrosleep
Therapy" (1950s)
"Brain
Polarization"(1970s)
"tDCS"
(2000)

Mechanism of action
tDCS
can
modify
neuro
plasticity
by
Glutamate
rgic/GABA
ergic/
other NT
mediated
effects
Increasing
or
decreasin
g the
neuronal
conductivit
y
Differential
ly acting
on
neuronal
sites
Modulatin
g the local
blood flow
BDNF
dependent
mechanis
ms

 Major depressive disorder
 Persistent auditory
hallucinations in
schizophrenia. Possibly for
positive and negative
symptoms.
 Craving in alcohol
dependance and tobacco
smoking: Relapse prevention
 Obsessive-compulsive
disorder
 Mild cognitive impairment and
dementia
 Structural head injury
 Epilepsy in patient/family
 Scalp injury/skin lesions
 Implanted medical devices
 Foreign body in head/eyes
 Past history of adversities
with tDCS/rTMS
Indications Precautions

 Had any adverse reaction to TMS/tDCS, if received earlier?
 Had a seizure/epilepsy?
 Had an unexplained loss of consciousness?
 Had a stroke?
 Had a serious head injury?
 Had a surgery to your head?
 Had any brain-related, neurological illnesses?
 Do you suffer from frequent or severe headaches?
 Do you have any metal in your head (outside the mouth) such as shrapnel,
surgical clips, or fragments from welding?
 Do you have any implanted medical devices such as cardiac pacemakers or
medical pumps?
 Are you taking any medications?
 Are you pregnant?
 Does anyone in your family have epilepsy?
Safety screening questions

Written informed
consent
Dry, clean, non-oily scalp required
for tDCS session
fasting or other lifestyle changes
are not needed
Pre-administration preparations

Pre-administration preparations
Ensure the device has enough power for completion of the
session.
Visually inspect the rubber electrodes for signs of wear and tear.
Place the rubber electrodes in sponge casings to improve
tolerability and reduce adverse events like tissue injury.
Never place the electrodes directly on the scalp.
Apply the non-conductive water-proof bands for holding
electrodes securely on the subject’s head.
Thoroughly inspect the subject’s scalp for signs of skin lesions,
cuts, signs of inflammation or other cutaneous abnormalities.

Administration procedure
Seat the subject comfortably in a chair.
Localize the stimulation target regions on the subject’s head10-20 EEG system
Mark the point on the subject’s scalp that corresponds to target
locations.
Part the hair at this marking as thick hair can cause higher impedance.
Switch on the device before placing the electrodes on the scalp surface to avoid
sudden surge of current in the circuits.
Smooth surface of the electrode should be in contact with the scalp.

Administration procedure
Sponge should be sufficiently damp to be properly conductible and the
electrode should be placed inside the sponge.
Carefully place the cathodal and anodal electrodes on the mark for
desired/marked target regions at an appropriate orientation
The wire connected to the electrode should be posteriorly directed in the
attachment.Ascertain the distance between the two electrodes is
minimum 7 cm (3 finger distance).
Set-up the electrical parameters and initiate the treatment.

Protocol for tDCS
Diagnosis Anode Cathode Duration Sessions
Schizophrenia Left DLPFC Left TPJ 20min 2 per day x 5
days
OCD Pre SMA Right
supraorbital
20min 2 per day x 5
days
Craving Right DLPFC Left DLPFC 20min 1 per day x 5
days
Depression Left DLPFC Right DLPFC 30min 1 per day x 10
days
Dementia/MCI Left DLPFC Right
supraorbital
20min 1 per day x 5
days

Adverse effects
 Headache
 Neck and scalp pain
 Tingling, Itching, Burning sensation
 Skin redness and lesions
 Sleepiness and Trouble concentrating
 Acute mood changes
 Disturbed visual perception
 Discomfort (during tDCS)
 Flashes (Phosphenes)

Applications of tDCS in
psychiatry
 Major Depressive Disorder
 Anode is placed over left DLPFC and cathode
over right DLPFC
 tDCS has been found to elicit similar
antidepressant effects to 20mg of fluoxetine
 Bipolar Disorder
 left prefrontal anodal stimulation in bipolar
depression
 Anodal tDCS over right DLPFC in manic
symptoms

psychiatry
 Schizophrenia –
 significant reduction of auditory hallucinations
after anodal tDCS over the left DLPFC and
cathodal stimulation over the left temporoparietal
region
 Substance use disorder –
 tDCS over the DLPFC has been shown to be
clinically useful in the treatment of drug addiction,
with DLPFC being an important brain structure for
the regulation of craving behavior

psychiatry
 Anxiety disorders –
 With the DLPFC being also involved in threat
processing, tDCS over the DLPFC might be an
effective treatment option for anxiety disorders
 Combination of tDCS with CBT is a good option
for anxiety disorders

Introduction
 Introduced in the 1990s
 By Benavides ET AL
 Neurosurgical procedure involving the
implantation of a medical device called a
neurostimulator
 sends electrical impulses, through implanted
electrodes, to specific targets in the brain
(brain nuclei)
 for the treatment of movement and
neuropsychiatric disorders

 Written informed consent to be taken
 The patient will need to be medically cleared
to undergo surgery
 Brain-imaging studies to visualize locations for
implantation of the electrodes.
Preparation

Technique
The surgical team will fit the patient with a stereotactic head frame to immobilize
head movement during the surgery
performed under general anesthesia (local anesthesia can also be used)
The surgeon then implants a thin wire lead to the structures that were identified
pre-surgery. Tiny electrodes at the end of the wire will contact the target
structures.
The lead is then connected to a wire which runs just superficially to the skin,
which ultimately connects to a pulse generator within the chest wall.
The subsequent chest wall surgery involves the placement of the pulse
generator just under the skin near the clavicle. (Requires general
anaesthesia)
The pulse generator is then connected to a special remote control.

Post surgery patient care
 can develop during the first few
weeks or even months after
surgery.
 Hardware related complications
 Lead migration
 Lead fracture
 Lead erosion
 Lead malfunction
 Malfunctioning of neurostimulator
 Seizures
 Dystonia
 Hemorraghe
Complications Precautions
 Precautions that you can take to
prevent an infection include the
following
 Never scratch, touch, or put
any pressure on the incision
 Be sure pillows, sheets, and
bedding are clean
 Keep the stitches clean and
dry
 Return to have sutures or
staples removed at the
schedule time
 Look for sign of infection

Indications
 Parkinson disease
 Essential tremor
 Dystonia
 Epilepsy
 Tournette syndrome
 Ocd
 Chronic pain

Role of DBS in movement
disorders
 Thalamus for
tremors
 Subthalamic
nucleus (STN) and
GPi for PD and
dystonia
 Pedunculopontine
nucleus for postural
instability

Role of DBS in psychiatry
 Obsessive compulsive disorder-
Targets of stimulation are
 Ventral capsule/ventral striatum
 Nucleus accumbens
 Subthalamic nucleus
 Inferior thalamic peduncle

 Treatment resistant depression-
 Subcallosal cingulate white matter
 Ventral capsule/ ventral striatum
 Nucleus accumbens
 Inferior thalamic peduncle
 Stria medullaris thalami

 Addiction –
 Role of nucleus accumbens
DBS in nicotine addiction and
alcoholism
 Alzheimers disease –
 Fornical/ hypothalamic DBS
has showed potential efficacy
 Tourette’s syndrome –
 DBS of GPi or VC/VS is also
efficacious for treatment
refractory TS
 Thalamic DBS showed
significant decrease in tic
severity, PC symptoms,
anxiety and depression

Contraindications
 Deep brain stimulation (DBS) has fairly
minimal absolute contraindications.
 DBS is contraindicated in patients who cannot
properly operate the neurostimulator.
 Once implanted, patients with deep brain
stimulators should not undergo full-body
magnetic resonance imaging scans (MRIs),
transcranial magnetic stimulation, and
diathermy

References
 Mishra BR, Sarkar S, Praharaj SK, Mehta VS, Diwedi S, Nizamie SH. Repetitive
transcranial magnetic stimulation in psychiatry. Ann Indian Acad Neurol. 2011
Oct;14(4):245-51. doi: 10.4103/0972-2327.91935. PMID: 22346010; PMCID:
PMC3271460.
 Mann SK, Malhi NK. Repetitive Transcranial Magnetic Stimulation. [Updated 2023 Mar 6].
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
 Chail A, Saini RK, Bhat PS, Srivastava K, Chauhan V. Transcranial magnetic stimulation: A
review of its evolution and current applications. Ind Psychiatry J. 2018 Jul-Dec;27(2):172-
180. doi: 10.4103/ipj.ipj_88_18. PMID: 31359968; PMCID: PMC6592198.
 Holtzheimer PE, Mayberg HS. Deep brain stimulation for psychiatric disorders. Annu Rev
Neurosci. 2011;34:289-307. doi: 10.1146/annurev-neuro-061010-113638. PMID:
21692660; PMCID: PMC4413475.
 Sreeraj VS, Arumugham SS, Venkatasubramanian G. Clinical Practice Guidelines for the
Use of Transcranial Direct Current Stimulation in Psychiatry. Indian J Psychiatry. 2023
Feb;65(2):289-296. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_496_22. Epub 2023
Jan 30. PMID: 37063621; PMCID: PMC10096202.
 Sironi VA. Origin and evolution of deep brain stimulation. Front Integr Neurosci. 2011 Aug
18;5:42. doi: 10.3389/fnint.2011.00042. PMID: 21887135; PMCID: PMC3157831.

Mcqs
 What is the primary mechanism of action of
transcranial magnetic stimulation (TMS) in
altering brain activity?
A) Direct modulation of neurotransmitter levels
B) Induction of controlled seizures
C) Generation of electrical currents in neural
tissue
D) Activation of specific brain regions through
magnetic resonance imaging (MRI)

Mcqs
 What is the primary effect of low-frequency
transcranial magnetic stimulation (TMS) on
cortical excitability?
A) Increase in excitability
B) Induction of synaptic plasticity
C) Inhibition of excitability
D) Promotion of neurogenesis

Mcqs
 In addition to major depressive disorder
(MDD), which other neurological condition has
received FDA approval for treatment with
repetitive transcranial magnetic stimulation
(rTMS)?
A) Bipolar disorder
B) Schizophrenia
C) Obsessive-compulsive disorder (OCD) D)
D) Parkinson's disease

Mcqs
 In addition to major depressive disorder
(MDD), which other neurological condition has
received FDA approval for treatment with
(rTMS)?
A) Bipolar disorder
B) Schizophrenia
C) Obsessive-compulsive disorder (OCD)
D) Parkinson's disease

Mcqs
 A 30-year-old female with severe depression is considering
repetitive transcranial magnetic stimulation (rTMS) as a
treatment option. She reports having a metal plate implanted
in her skull following a traumatic brain injury sustained in a
car accident several years ago. What is the most appropriate
course of action?
A) Proceed with rTMS treatment, as metal implants are not a
contraindication.
B) Perform a thorough evaluation of the location and
composition of the metal implant before proceeding.
C) Advise against rTMS treatment due to the risk of
interference with the magnetic field.
D) Refer the patient to a neurosurgeon for removal of the metal
plate prior to rTMS treatment.

Mcqs
 Which type of coil is commonly used in
(rTMS) for targeting deep brain structures?
A) Figure-of-eight coil
B) Circular coil
C) H-coil
D) Butterfly coil

Mcqs
 During transcranial direct current stimulation
(tDCS), which electrode is typically placed
over the area to be stimulated?
A) Anode
B) Cathode
C) Ground
D) Reference

Mcqs
 What is the purpose of using saline-soaked
sponges or gel with electrodes during
transcranial direct current stimulation (tDCS)?
A) To increase electrical resistance.
B) To decrease electrical resistance.
C) To prevent skin irritation.
D) To enhance electrode conductivity.

Mcqs
 Which of the following is a potential advantage
of transcranial direct current stimulation (tDCS)
over other brain stimulation techniques?
A) Higher risk of inducing seizures
B) Non-invasiveness
C) Requirement for surgical implantation
D) Limitation to targeting superficial brain
regions

Mcqs
 Which of the following neurological conditions
is commonly treated with deep brain
stimulation (DBS)?
A) Depression
B) Alzheimer's disease
C) Parkinson's disease
D) Migraine

Mcqs
 During deep brain stimulation (DBS) surgery,
electrodes are implanted into specific brain
regions, and a pulse generator is usually
placed in the:
A) Chest
B) Abdomen
C) Scalp
D) Wrist

Mcqs
 In deep brain stimulation (DBS) surgery, local
anesthesia is typically administered to numb
the:
A) Scalp and skull
B) Entire body
C) Muscles surrounding the brain
D) Peripheral nerves

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