Slow repetitive Transcranial
Magnetic Stimulation
A Treatment for Auditory Hallucinations in
Schizophrenia
Transcranial Magnetic Stimulation
(TMS)
Historical Background:
 About a century ago researchers
first stimulated retinal nerve cells
with magnetic fields to produce
flashes of light in subjects
 1985 Barker and colleagues first
stimulate brain cells in the motor
cortex of subjects.
 By 1990’s develop repetitive TMS
where repeated magnetic pulses
can be delivered up to 50 times a
second (50 hertz)
Thompson, 1910
Transcranial Magnetic Stimulation
(TMS)
About the intervention:
 Principle behind TMS is if an electrical current is passed
through a wire coil, then it momentarily generates a
magnetic field.
 This magnetic field can easily penetrate the skull and
induce electrical currents in the brain that can depolarize
superficial neurons
 The magnetic field rapidly declines with distance
 Stimulates about 2-3 cm of cortex but depends on shape
and configuration of coil (Hoffman & Cavus, 2002)
 So this is a relatively painless and non-invasive way to
stimulate the brain
Transcranial Magnetic Stimulation
(TMS)
About the intervention:
 2 types of rTMS: fast rTMS is >1 hertz
slow rTMS is ≤ 1 hertz
 Fast rTMS induces excitation whereas slow rTMS
induces inhibition in brain cells. Reasons for this isn’t
clear
 Slow rTMS may bring about lasting changes as well
(Chen et al, 1997)
 Based on this researchers have begun to use slow
rTMS to treat brain hyperexcitability disorders like
auditory hallucinations (AH) in Schizophrenia
Procedure of Studies
 Slow rTMS (1 hertz), was administered to the left




temporoparietal cortex, (which has been shown to be
active during AH), of right handed patients for up to about
15min a session for about 1-2 weeks
Patients had Schizophrenia and reported AH on a daily
basis
Patients AH were assessed by the Auditory Hallucinations
Rating Scale (AHRS), developed by Hoffman et al., before,
during and after the treatment
In a double blind protocol, patients were randomly
assigned to either the treatment or sham condition
Sham condition was the same as treatment except the coil
was angled 45° from the scalp. This produced the same
sounds and feeling of ‘knocking on the scalp’, but without
the brain stimulation.
Research studies
Transcranial magnetic stimulation and auditory
hallucinations in schizophrenia (Hoffman et al, 2000)
 Studied 12 Schizophrenic
patients with AH and used a
double-blind crossover design
with a sham-stimulation control
condition
 the effects of 4, 8, 12, and 16
minutes of stimulation
administered on four separate
days were assessed.
 Improvements in AH were
significantly greater for rTMS
than sham in the 12 and 16
Research studies
Transcranial magnetic stimulation and auditory
hallucinations in schizophrenia (Hoffman et al, 2000)
Possible Limitations:
 Possible individual differences in anatomical location of
primary speech area
 Patients who receive rTMS condition first might have
effects on sham condition
 5 patients were taking anticonvulsant drugs and this
seemed to have an affect on reduction of AH after rTMS
 rTMS at 45° in sham condition may still be active on
cortex
Research studies
Temporoparietal Transcranial Magnetic Stimulation for
Auditory Hallucinations: Safety, Efficacy and Moderators
in a Fifty Patient Sample (Hoffman et al., 2005)
Studied 50 schizophrenic
patients with AH and used a
double-blind random assignment
to either active or sham condition
Excluded patients with history of
seizures
Trials lasted 8mins on day 1,
12mins on day 2, and 16mins on
subsequent 7days
AH were significantly reduced in active
compared to sham condition
Research studies
Temporoparietal Transcranial Magnetic Stimulation for
Auditory Hallucinations: Safety, Efficacy and Moderators
in a Fifty Patient Sample (Hoffman et al., 2005)
Possible Limitations:
 Possible individual differences in anatomical location
of primary speech area
 Half the patients were recruited on a previous study
so recruiting procedures could have changed
 Patients were taking various neuroleptics during this
study which might have had an interaction
 rTMS at 45° in sham condition may still be active on
cortex
Research studies
Slow Transcranial Magnetic Stimulation Can Rapidly
Reduce Resistant Auditory Hallucinations in
Schizophrenia (Poulet et al., 2005)
 Studied 10 Schizophrenic
patients with AH in a
double-blind cross over
 Gave 1000 stimulations
twice a day for 5 days, for
each condition
 Roughly twice as much
stimulation as Hoffman et
al., in half the time
Found a significant reduction in AH
Also used a real sham stimulator
Research studies
Slow Transcranial Magnetic Stimulation Can Rapidly
Reduce Resistant Auditory Hallucinations in
Schizophrenia (Poulet et al., 2005)
Possible Limitations:
 Possible individual differences in anatomical location
of primary speech area
 Patients who receive rTMS condition first might have
effects on sham condition
 The more intense sessions might have increased risk
of adverse effects
 A few patients were taking anticonvulsant drugs
which was shown in Hoffmann et al., (2000) to affect
rTMS on AH
Research studies
Transcranial magnetic stimulation for auditory hallucinations in
Schizophrenia (McIntosh et al., 2004)
 Replicated Hoffman et al, 2000
 Studied 16 Schizophrenic patients with AH and used a
double-blind crossover design
 the effects of 4, 8, 12, and 16 minutes of stimulation
administered on four separate days were assessed
 Each minute of stimulation was followed by 15 seconds of
rest to check coil position and allow patients to move
 Patients AH improved in both active and sham with no
significant difference
 So they failed to replicate Hoffman et al., results
Research studies
Transcranial magnetic stimulation for auditory hallucinations in
Schizophrenia (McIntosh et al., 2004)
Possible Limitations:
 The 15 seconds of rest after each minute may have
curtailed the physiological effects of rTMS
 Possible individual differences in anatomical location of
primary speech area
 Patients who receive rTMS condition first might have
effects on sham condition
 rTMS at 45° in sham condition may still be active on cortex
Research studies
Neuronavigated transcranial magnetic stimulation and
auditory hallucinations in a schizophrenic patient: Monitoring
of neurobiological effects (Langguth et al., 2005)
 A case study of a male with disorganized Schizophrenia
with AH who was not responding to neuroleptics or CBT
 Decided to try rTMS
 First a PET and MRI was done to find the exact area of
activation during AH
 This allowed the TMS coil to be exactly positioned over the
site of increased activation in the left temporal cortex
 28 sessions of 2000 stimuli were administered and PET
was followed up after 2 and 5 weeks
 The PET scans revealed an attenuation of the initial
increased activation compared with normals
Research studies
Neuronavigated transcranial magnetic stimulation and
auditory hallucinations in a schizophrenic patient: Monitoring
of neurobiological effects (Langguth et al., 2005)
 This study shows that neuroimaging is suitable for
detecting changes in auditory processing and for AH
 This study and previous studies show that the superior
temporal gyrus is important in the pathophysiology of AH
 Also neuroimaging before rTMS can circumvent the
problem of individual differences in anatomical location of
auditory area’s involved in AH
 Although this is only a case study
Neurobiology of the Disorder
 Auditory Hallucinations (AH) occur in 60 – 80% of people
with Schizophrenia (Hoffman et al., 2005)
 Neuroimaging studies show that activation of brain areas
involved in speech perception play a role in producing AH
 Dierks et al., (1999) showed that primary auditory cortex
is activated in hemisphere dominant for handedness
during AH and bilaterally during acoustic stimulation
 Lennox et al., (2000) showed that superior temporal,
middle frontal and inferior parietal gyri were activated
during AH
Neurobiology of the Disorder
 Slow rTMS is thought to reduce AH because it induces




long term depression (Hoffman et al., 2002)
Long-term depression (LTD) and long-term potentiation
(LTP), are hypothesized to mediate information storage in
the brain, by enduring modifications in synaptic strength
LTP can be induced by high-frequency stimulation (40-100
hertz), where potentiated synapse are more likely to
produce an action potential and can last from hours up to
years
Whereas LTD can be induced by low-frequency stimulation
(1 hertz), and synapses are weakened making it less likely
for an action potential.
Furthermore, low-frequency stimulation is able to reverse
high-frequency-induced potentiated synaptic responses, a
phenomenon referred to as “depotentiation,” (Hoffman et
al., 2002)
Neurobiology of the Disorder
 Slow rTMS is thought to induce LTD because it produces




the same low frequency (1 hertz) stimulation in brain cells
as direct electrical stimulation
This would explain why Slow rTMS (≤ 1 hertz) induces
inhibition whereas fast rTMS (>1 hertz) induces excitation.
Also low frequency direct electrical stimulation over many
days has been shown to induce longer periods of LTD,
which is also seen in slow rTMS over many days (Hoffman
et al., 2002)
So this means that slow rTMS reduces AH by reducing the
synaptic strength in the auditory cortex through LTD
Although LTD is simply not enough to completely explain
the effects of slow rTMS on the complex intracortical
circuitry
Evaluation
Advantages:
 It’s a non-invasive way that may produce somewhat
long lasting changes in brain disorders like
Schizophrenia, through depotentiation
 Doesn’t have the side effects of drugs, as long as safety
guidelines are followed
 Provides precise information on functional significance
of specific brain regions
 Can establish causal link between brain activation and
behaviour
Evaluation
Disadvantages:
 Strict ethical guidelines must be followed
 Magnetic fields will disrupt electrical devises like pace
makers, etc.
 Can cause hearing loss because sound emitted is in
the frequency range 2–7 kHz where the human ear is
the most sensitive, so must wear ear plugs
 Can cause headache because of activation of scalp
and neck muscles
 TMS operates at high voltages so must be careful
around equipment
 Can possibly cause seizure with fast rTMS
Conclusion
 I believe that TMS is a very promising new method to
study normal and abnormal brain functioning and to
treat various mental disorders
 Although not all patient groups can receive TMS (i.e.
patients with seizure disorders)
 More studies need to be done to clarify the effects of
slow rTMS on the brain
 Intervention studies with TMS should use patient
specific neuroimaging to circumvent individual
anatomical differences and to enhance outcome