about rTMS and literature review

1. rTMS TECHNIQUE AND
CURRENT STATUS
Dr. Shravan Kumar

2. INTRODUCTION
• Following the discovery of the unified and interchangeable
nature of electric and magnetic forces, it became evident that
electric currents generate magnetic fields while changing
magnetic fields generate electric currents.
• Galvani’s and Volta’s classic experiments had established that
electric currents were capable of stimulating neuronal tissues.
• The combination of these two concepts – the unity of electric
and magnetic forces, and the responsiveness of neurons to
electrical stimulation – is now being harnessed to study and
manipulate the CNS from neuropsychiatric perspectives.

3. • TMS uses an externally generated changing magnetic field to
induce electric current intracranially unlike ECT where an
electric current that is generated externally and transmitted to
the brain through the skull.
• When electricity is forced to pass through the skull, the current
used must be relatively large as the skull is a powerful
insulator with an electrical resistance 8 to 15 times greater than
that of soft tissues.
• Externally generated electric currents cannot be focally
directed as the skull dissipates the electricity globally leading
to massive depolarization of cortical and subcortical structures.

4. • Such difficulties are minimized upon exposure of the skull to
TMS, where the changing external magnetic field undergoes
minimal attenuation in the skull tissues while inducing smaller,
focally directed electric currents within the brain.
• Barker et. al. first described in 1985 the use of a pulsed (i.e.
changing) magnetic field focused over specific regions of the
cerebral cortex to induce muscle action potentials.
• The use of pulsed magnetic fields to induce electrical activity
in peripheral nerves had been described much earlier, in the
1960’s.

5. • The higher frequency technique has been found to be
particularly effective in neuropsychiatry and has been termed
Repititive Transcranial Magnetic Stimulation (rTMS).
• rTMS is believed to be unique in that rapid pulsation can
induce electrical currents within neurons while they are in the
refractory period, although how this relates to an altered
clinical manifestation is unclear.
• The magnetic field, passing largely unimpeded through the
skull, induces a current within the brain tissue.
• Depending on the region of the brain over which the coil is
physically placed, specific circumscribed areas can be
stimulated.

6. • TMS has been used for multiple purposes in the field of
neurology including establishing hemispheric language
dominance, localization of epileptogenic foci, and the study of
motor pathways originating at the cerebral cortex and relevant
motor pathway physiology.
• It has also been utilized in neuropsychiatry in the mapping of
attention, memory, movement, speech, and vision.

7. • Clinically, TMS has been combined with electromyographic
studies (EMG) to determine impairment in CNS conduction
pathways by measuring differences in the rates of muscle
activation upon electromagnetic stimulation at the cerebral
cortex in comparison with similar stimulation at spinal nerve
roots.
• This assessment is useful in the diagnosis and prognostication
of demyelinating diseases such as multiple sclerosis.
• More recent efforts have focused on the use of TMS in the
symptomatic improvement of Parkinson’s disease.

8. • Being a relatively new technique, optimization of parameters
such as frequency of pulsing of the magnetic field, size of the
coil utilized, strength of the magnetic field generated, and
duration of induction of electrical current has yet to be
established.
• It is likely that such parameters will vary substantially
depending on the specific neurological or psychiatric
applications.

9. PRINCIPLE OF TMS
• TMS works on the Faraday’s law which states that “The
induced EMF in any closed circuit is equal to the rate of
change of the magnetic flux through the circuit.”
TMS Magnetic
field
Induced neuronal current

10. TMS is a non-invasive method of brain stimulation in which
magnetic fields are used to induce electric currents in the
cerebral cortex, thereby depolarizing neurons.
Uses a rapidly changing magnetic field to induce weak electric
currents, through pulses.
Induced by electromagnetic induction
Generally reach no more than 5cm into the brain

11. • The stimulators and coils currently in production develop
about 1.5–2 T at the face of the coil and are thought to be able
to activate cortical neurons at a depth of 1.5–2 cm beneath the
scalp (Epstein et al., 1990).
• Even though TMS with conventional equipment appears to
penetrate no deeper than the cortex, it may affect cells trans-
synaptically at some distance from the site of stimulation, as
evidenced by its effect on distant cortical and subcortical sites
detected with PET (Kimbrell et al., 1997; Paus et al., 1997;
Wassermann et al., 1997).

12. • Single-pulse magnetic stimulators repeat pulses no faster than
once every few seconds.
• Faster cycling is prevented by the charging time of the
capacitors, which store the electrical charge that generates the
current in the coil.
• In the last 10 years, stimulators using multiple capacitors and
capable of generating pulses at up to 60 Hz have been
introduced.
• High-frequency stimulation can also be produced by multiple
stimulators that discharge through a single coil and are
triggered in sequence by a microprocessor.

13. • The number of pulses that these systems can deliver in a single
train may be limited by the number of stimulators, but very
high pulse frequencies are possible.
• Heating of the coil is a problem that potentially endangers
subjects as well as equipment and limits the duration of
stimulation at high intensities and frequencies.

14. • The underlying rationale for the use of TMS exploits the fact
that neurons are electrochemical cells.
• This means that neuronal activity can be affected either
chemically, via the use of drugs, or electrically, via
interventions like TMS.

15. Neuron
TMS Directly Depolarizes Cortical Neurons
Pulsed magnetic
fields from TMS:
• induce a local
electric current in
the cortex which
depolarizes
neurons
• eliciting action
potentials
• causing the release
of chemical
neurotransmitters
Neurons are
“electrochemical cells”
and respond to either
electrical or chemical
stimulation

16. TMS Releases Neurotransmitters
in the Brain
Depolarization of neurons in the DLPFC
causes local neurotransmitter release
Depolarization of
pyramidal neurons in the
DLPFC also causes
neurotransmitter release
in deeper brain neurons
Activation of deeper brain neurons then
exerts secondary effects on remaining
portions of targeted mood circuits
Dorsolateral
prefrontal
cortex
Anterior
cingulate
cortex
Kito (2008) J Neuropsychiatry Clin Neurosci
These effects are
associated with
improvements in
depressive
symptoms

17. PHYSIOLOGICAL EFFECTS OF TMS
OVER BRAIN
– Neuronal excitation activity (facilitation)
– Neuronal inhibition activity (silent period)
– Stimulation of one site but get inhibition at another
site (interhemispheric inhibition)
– long-term post-stimulation effect
(long-term penetration)

18. FACILITATION

19. SILENT PERIOD (SP)

20. IHI (INTERHEMISPHERIC
INHIBITION)

21. NEUROBIOLOGICAL EFFETS OF
TMS
• TMS targets modulation in neuroplasticity to influence
behavior consequences.
NEUROPLASTICITY:
• The capacity of the brain to change with learning is known as
plasticity.
• This is the brain’s ability to reorganize itself by forming new
neural connections throughout life.
• It allows the neurons in the brain to compensate for the injury
and disease, and to adjust their activities in response to new
situations or to changes in their environment.

22. • Brain reorganization takes place by mechanisms such as
“axonal sprouting” in which undamaged axons grow new
nerve endings to reconnect neurons whose links were injured
or severed.
• Undamaged axons can also sprout nerve endings and connect
with other undamaged nerve cells, forming new neural
pathways to accomplish a needed function.
• In order to reconnect, the neurons need to be stimulated
through activity.

23. • Neuroplasticity allows brain to compensate for irreparably
damaged or dysfunctional neural pathways by strengthening or
rerouting of remaining ones.
COMPENSATORY MASQUERADE
•Allows already constructed pathways that neighbor a
damaged area to respond to changes in the body’s demands
caused by lost function in some other area.

24. HOMOLOGOUS REGION ADOPTION
•allows one entire brain area to take over functions from
distant brain areas that has been damaged.
CROSS MODEL REASSIGNMENT
•allows the brain of a blind individual in learning to read
Braille, to rewire the sense of touch so it replaces the
responsibilities of vision in the brain areas linked with
reading.

25. TMS DEVICE

27. TYPES OF COILS

28. Electric field intensity induced below the coils of
different types

29. GENERAL RULES FOR SELECTING
THE APPROPRIATE COIL FOR CERTAIN
APPLICATION
– Small coils have stronger field on the surface but
field decreases dramatically with distance. Therefore
small coils are suitable for peripheral stimulation in
which magnetic field does not need to pass through
skull bones.

30. – Big coils have lower decrease of field with distance.
Therefore they are used for transcranial stimulation.
– Ring coils are less focused. Therefore they are used
for stimulation of wide areas (for diagnostics).
– Figure-of-eight coils are more focused, therefore they are
widely used for treatment.

31. STIMULATION POINT AND COIL
ORIENTATION IN DEPRESSION TREATMENT

32. TYPES OF TMS
• Single-Pulse TMS – Delivers one stimulus at a time
• Paired-Pulse TMS – Pairs of stimuli separated by a variable
interval
• Repetitive TMS (rTMS) – Delivered in trains (can be of low
or high frequency)

33. LOW FREQUENCY VS. HIGH
FREQUENCY TMS
Concept of Depolarization Function
• Low Frequency Stimulation--inhibitory, more focal effect
• High Frequency Stimulation--facilitatory, multiple spread
out, global “dendritic/axonal effect”.
When higher frequency rTMS is applied, a longer lasting effect
can be induced which is thought to result from a long term
potentiation (LTP), or depression (LTD) at the neuronal level.
33

34. APPLICATIONS OF TMS
• Diagnostic
• Therapeutic

35. DIAGNOSTIC
• 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 other lesions to generate preoperative
motor maps

36. • Main Techniques:
– Amplitude of motor evoked potential (MEP)
– Amplitude ratio (motor evoked potential/M-wave)
– Motor evoked potential facilitation
– Central motor conduction time
– Triple stimulation test

38. Diagnostically, the only FDA approval is the Navigated Brain
Stimulation System for pre-surgical planning in patients
undergoing brain surgery.
Proven equally successful as traditional imaging methods in
producing preoperative motor maps.
When compared to direct cortical stimulation (DCS), it was
found that TMS was able to recognize every motor site
mapped by DCS

39. THERAPEUTIC TMS USE
• Amblyopia
• Amyotrophic lateral sclerosis
• Auditory hallucinations associated with schizoaffective
disorders
• Chronic pain
• Dysphasia
• Dystonia
• Epilepsy
• Fibromyalgia

40. • Hemispatial neglect
• Major depression
• Migraine
• Obsessive-compulsive disorder
• Parkinson’s disease
• Phantom limb
• Stroke
• Nonfluent aphasia
• Tinnitus

41. • FDA has currently only approved rTMS as a treatment for
Major Depressive Disorder (MDD).

42. RECENT TMS LITERATURE REVIEW
• Roughly 30 controlled clinical research studies to date
• Most recent meta-analysis (Slotema, et al, 2010):
– Included analysis of 34 studies involving 1,383 patients
– Estimated standardized effect size = 0.55 (P < 0.001)
Conclusion: “…rTMS deserves a place in the standard toolbox
of psychiatric treatment methods, as it is effective for
depression…and has a mild side effect profile….”
1.Slotema, CW, Blom, JD, Hoek, HW, Sommer, IEC. (2010) Should we expand the
toolbox of psychiatric treatment methods to include repetitive transcranial
magnetic stimulation (rTMS)J Clin Psych 71(7):873-84.
1.Schutter, DJLG. (2009) Antidepressant Efficacy of High-Frequency Transcranial Magnetic Stimulation Over the
Left Dorsolateral Prefrontal Cortex in Double-Blind Sham-Controlled Designs: A Meta-Analysis. Psychol
Medicine, 39:65-75.

43. • Independent, Peer-reviewed
• 15 TMS clinical trials involving nearly 500 patients
– Average HAM-D decrease in depressive symptoms >5 points
vs. Sham control
• Meets clinical significance threshold of 3 points on the
HAM-D scale
– Response rate with active TMS was >3x higher than sham
treatment
– Remission rate with active TMS was >6x higher than sham
treatment
• “High strength of evidence” for efficacy from well-controlled
RCTs
Independent U.S. Agency for Healthcare Research And
Quality (AHRQ) confirms evidence for efficacy of TMS
Agency for Healthcare Research and Quality: Comparative Effectiveness Report
on Non-Pharmacologic Treatments for Depression , October 2011

44. • Ebmeier and colleagues - conducted a 5-day study with 15
patients that called for them to be treated twice per day. At
the end of the study, the participants saw a reduction of 44%
on Hamilton-D scales.
• Another trial testing 100 patients, however, saw most to be
treatment-resistant.
• Current trials include using TMS with: autism, MDD,
improving speech aphasia

45. • In an open-label trial (most like real world clinical practice),
– 1 in 2 had a significant improvement in symptoms
– 1 in 3 had complete symptom resolution
• Patients also experienced significant improvement in anxiety,
appetite changes, aches and pains, and lack of energy
associated with depression
• Over 10,000 procedures performed in clinical trials
• No systemic side effects such as weight gain, sexual
dysfunction, nausea, dry mouth, and sedation

46. PROTOCOLS FOR DEPRESSION
TREATMENT
•The majority of trials apply Neuro-MS to treat depression using
these protocols:
Over the left frontal dorsolateral cortex (5 cm anterior (parallel to
the sagittal line) to the area where the motor threshold is
obtained) 5 Hz, 25 trains of 10 seconds each with 20-second
pause between the trains.
Applied at 120% of the motor threshold (protocol used by Dr.
Marcolin).
OR

47. •10 Hz, 30 trains of 4 seconds each with 20-second pause
between the trains.
•Applied at 100% of the motor threshold (or 120%, when
possible limited by
the power of the device) (protocol used by Dr. Moacyr).
•The quantity of stimuli for effective treatment is considered
as more than 1000 pulses
•Number of sessions: 15-30 (3-6 weeks)

48. LONG TERM FOLLOW UPAFTER
ACUTE TREATMENT
Janicak, et al. Brain Stimulation, 2010.
• Safety confirmed during long term, open-label 6 month follow up
period
• During open-label follow up on antidepressant medication
monotherapy,
– ~37% of patients required TMS reintroduction
– ~85% of patients who received TMS reintroduction benefited
• Net incidence of illness relapse under these open-label
follow up conditions: 11%
– Six-month relapse with antidepressant treatment alone in STAR*D study was 35-
50% (Level 2 and 3 range)

49. TMS OPEN-LABEL DURABILITY OF
EFFECT STUDY
Outcome
TMS
(in remission)
(N=56)
Outcome
ECT - Combination
Pharmacotherapy 1
(N=95)
ECT - Continuation
ECT 1
(N=89)
% Early
Discontinuation 16.1%
% Early
Discontinuation 22.1% 16.8%
% Disease
Recurrence 10.7%
% Disease
Recurrence 31.6% 37.1%
% In Remission
by Study
Completion
73.2%
% In Remission by
Study Completion 46.3% 46.1%
1 Kellner, CH, Knapp, RG, Petrides, G, et al. Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse Prevention in Major Depression: A Multisite
Study From the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006, 63:1337-1344.
Janicak, et al., Brain Stimulation (2010)

50. • In research settings, two large, multisite, randomized controlled
trials demonstrated clinically significant antidepressant effect of
TMS.
• Prospective, naturalistic study confirms these results in real-
world practice settings.
• Overall, 1 in 2 patients respond and 1 in 3 patients achieve
remission.
SUMMARY OF CLINICAL
OUTCOMES
50

51. • Meta-analyses from multiple studies shows TMS effect size of
>0.5
• High level of treatment adherence , >80% of patients
completed acute treatment in both research setting and in
clinical practice.
• Appears to be at least as effective as ECT for treatment and
relapse prevention

52. NEW APA GUIDELINES
• Transcranial magnetic stimulation is now listed in the
American Psychiatric Association’s 2010 “Practice Guideline
for the Treatment of Patients with Major Depressive Disorder”
• It is listed as an acute phase treatment option for patients who
do not respond adequately to pharmacotherapy.
.

53. • This recent guideline states; “Acute phase treatment may
include pharmacotherapy, depression-focused psychotherapy,
the combination of medications and psychotherapy, or other
somatic therapies such as electroconvulsive therapy (ECT),
transcranial magnetic stimulation (TMS), or light
therapy.” (APA Guidelines 2010; Pg 46).

54. BEST PRACTICES TREATMENT
GUIDELINE FOR DEPRESSION
Based on 2010 APA guidelines and NeuroStar TMS Therapy® indication for
use.
Adapted from: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd Edition, APA (2010)
Unmet Medical
Needs

55. TMS THERAPY: SAFETY OVERVIEW
• No systemic side effects
• No adverse effect on cognition
• Most common adverse event associated with treatment was
scalp pain or discomfort
– < 5% of patients discontinued due to adverse events
• No seizures reported during clinical studies (over 10,000
treatments)
• Rare risk of seizure with NeuroStar TMS in post-market use
(0.003% per treatment, <0.1% per acute treatment course)
(>150,000 treatments in post-marketing experience to date)
• Long term safety demonstrated in 6 months follow-up

56. OTHER DISORDERS UNDER
EVALUATION FOR TMS THERAPY
• I. PSYCHIATRY: Depression (FDA approval,Oct 2008),
treatment refractory cases, co-morbid, Panic Disorder, OCD,
PTSD, pathologic gambling, substances use like cocaine,
opiates, nicotine, schizoaffective disorder.
• II. Chronic neuropathic pains, phantom
pain,fibromyalgia,Migraine,headaches, Tourette's, tinnitus,
painful dystonia.
• III. NEUROLOGY: Rehabilitation- after stroke , recovery-
Aphasia, Neglect, Brain Injury, Seizures

57. CURRENT
RESEARCH

58. rTMS - CURRENT FINDINGS
• rTMS upregulates BDNF in experimentally damaged area of
brain in mouse model
– Makowiecki K et al. J Neurosci. 2014 Aug6;34(32):10780-92
• 10Hz rTMS - improvement of freezing of gait in Parkinsonism
with stimulation over M1-LL and DLPFC in single session.
– Lee SY et al. Restor Neurol Neurosci. 2014 Jul 30.
• Use in treatment-resistant schizophrenia
– Miyajmoto S. et al. J Psychiatr Res. 2014 Jul 8.

59. TMS IN THE TREATMENT OF ADDITION
Gorelick DA et al. Ann NY Acad Sci. 2014 Jul 28
• 19 human studies reviewed, 316 adults
– Tobacco (9 studies), alcohol (6), cocaine (3), and
methamphetamine (1)
– Only FIVE studies were controlled tirals.
• 2 out of 45 nicotine trials = decreased smoking
• Cocaine trial = decreased use.
• Actions – “may involved increased dopamine and glutamate
function in corticomesolimbic brain circuits and modulation of
neural activity in brain circuits that mediate cognitive
processes relevant to addiction.”
• Considered experimental at present

60. A DOUBLE-BLIND, RANDOMIZED TRIAL
OF DEEP rTMS FOR AUTISM SPECTRUM
DISORDER.
Enticott PG et al. Brain Stimul. 2014 Mar-Apr;7(2):206-11
• 28 adults with high-functioning Autism or Asperger’s
– Double-blind, randomized, placebo controlled design
– 2 weeks of daily weekday treatment
– rTMS to bilateral dorsomedial PFC
• “Deep rTMS to bilateral dorsomedial PFC yielded a reduction
in social relating impairment and socially-related anxiety.”

61. IMPROVEMENT IN ALZHEIMER’S
Cotelli M et al. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7
• 10 AD patients randomized
– 4 weeks of rTMS
vs.
– 2 weeks of placebo followed by 2 weeks of real rTMS
• Protocol – 25 minute rTMS, DLPFC, weekdays.
• Significant difference was found between groups in terms of %
of correct responses of auditory sentence comprehension.
• rTMS may represent a novel approach to the treatment of
language dysfunction in AD patients.”

62. Ahmed MA et al. J Neurol. 2012 Jan;259(1):83-92.
• Study of high vs. low frequency rTMS applied bilaterally over
DLPFC on cognitive function and cortical excitability of AD
patients.
• 45 patients studied. 3 groups:
– Sham
– High frequency
– Low frequency
• “…five sessions of high frequency rTMS over the left and then
the right DLPFC improves cognitive function in patients with
mild to moderate degree of AD.
• This improvement was maintained for three months.”

63. POSITIVE EFFECTS OF rTMS ON
ATTENTION IN ADHD
Bloch Y et al. World J Biol Psychiatry. 2010 Aug;11(5)755-8
• Known that rTMS affects dopaminergic secretion in PFC.
• Double blind crossover randomized, sham controlled study of
13 patients (7 male, 6 female) – who fulfilled DSM-IV criteria.
• “There was a specific beneficial effect on attention 10 minutes
after a real rTMS course.”

64. TMS AS A RESEARCH TOOL
• A research tool to study aspects of the human brain physiology
including motor function,vision,language and the
pathophysiology of brain disorders.
• TMS can excite or inhibit the brain allowing functional
mapping of cortical regions and creation of transient functional
lesions.
• For eg.
 rTMS over the occipital lobe impaired detection of visual
stimuli
 rTMS delivered to discrete areas in the language-dominant
hemisphere can disrupt speech.

65. THERAPEUTIC APPLICATION IN
NEUROLOGICAL DISORDERS

66. MOVEMENT DISORDERS
• Therapeutic applications of TMS in movement disorders are
preliminary.
• Fast rTMS of the motor cortex has been reported to improve
performance on several motor measures in Parkinson disease.
• A recent meta-analysis included 12 studies and concludes that
the overall literature does show a positive effect of rTMS on
Parkinson motor function.
• Slow rTMS has been reported to improve dystonia.

67. NEURO-REHABILITATION
• TMS to evaluate the functional properties of the motor cortex
after lesions like stroke is of special interest in the field of
neuro rehabilitation.
• Brain stimulation have been proposed to enhance motor
function when combined with conventional neuro
rehabilitative interventions after stroke

68. CHRONIC PAIN
• rTMS of the cortex induces analgesic effects in focal chronic
pain syndromes (causalgia)

69. ADVERSE EFFECTS OF rTMS
• Risk of inducing seizures (in patients with a past or family
history of seizures).current safety protocols adjust the amount
of stimulation in relation to the motor threshold of the
individual.
• Muscle tension headache .
• Short term changes in hearing threshold related to the noise
generated.
• Cognitive changes only during stimulation

70. ECT vs. TMS
ECT TMS
Anesthesia, LOC Yes No
Induction of seizure Yes No
Systemic effects Anesthetic drugs,
increase HR
none
Treatment schedule 3X/ week (8 -15 tx) Daily, M-F, six weeks (30
tx)
Rapidity of onset 2 – 3 treatments 2 – 3 weeks
Mechanism of action SEIZURE. Massive NT
release; rise in sz
threshold
Reactivation of neural
circuits. Precise, LOCAL
release of NT’s.
Side effects Memory loss, confusion Essentially none (mild HA
1st week)
Psychosocial impact can’t work Drive to and from tx’s,
work improved
After-effects Mild (usually transient)
memory loss
None. Pro-cognitive
Insurance coverage Almost always Rare. Improving

71. CONTRAINDICATIONS TO TMS
• Metallic (Ferro or Paramagnetic) hardware near the coil can be
moved or heated by TMS. Therefore, the presence of metal
anywhere in the head, excluding the mouth, is generally a
contraindication to TMS.
• Individuals with cardiac pacemakers and implanted medication
pumps should not participate in rTMS studies without a clear
potential benefit (e.g., treatment of severe and refractory
depression).

72. • Children should not be used as subjects for rTMS without
compelling clinical reasons, such as the treatment of refractory
epilepsy or depression.
• Women of childbearing age must be questioned about the
possibility of pregnancy before participating in rTMS studies,
and excluded if there is a chance that they may be pregnant.
• Tricyclic anti-depressants, neuroleptic agents, and other drugs
that lower the seizure threshold are contraindications to rTMS,
except in extraordinary circumstances where the potential
benefit outweighs the increased risk of a seizure.

73. CONCLUSION
• TMS is a technique used to induce electrical current in neurons
by strong magnetic field.
• It is different from ECT where electrical current is applied
directly over the scalp and brain is stimulated.
• The induced current brings multiple immediate physiological
changes in neurons’ electrical activities and in long term
changes overall functioning of brain by various
neurobiological modulations in neuronal circuits.

74. • There are many diagnostic and therapeutic application of TMS
under trial in Neuropsychiatry.
• Currently this is approved only as second line treatment of
MDD and for resistant depression by FDA.
• Numerous meta analyses are present to support use of rTMS
in MDD therapy.
• In some studies TMS came out with comparable efficacy as
fMRI in tumor localisation and exploring focal deficits.
• We can expect many other applications to get approved in near
future.

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78. THANK YOU