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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5250_Библиотеки_им_академика_М_И_Перельмана.pdf
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7.2.3.4 Clinical Recommendations
The addition of a subthreshold stimulation pretreatment before the r TMS regimen
promises to be a new way to improve the efcacy of anti-compulsive therapy.
Moreover, the pretreatment of rTMS is easier to administer and more tolerable to
patients than more sequential and intense stimulation. It remains to be claried
whether the use of priming with low-frequency or high-frequency TMS initiation
will improve the efcacy of rTMS in patients with OCD.
7.2.4 Synchronized TMS
Synchronized TMS is a treatment modality in which a rotating spherical neodymium magnet is positioned along the midline of the scalp during TMS stimulation,
delivering synchronized stimulation according to an individual’s alpha frequency.
7.2.4.1 Efficacy
It has been shown that synchronizing TMS pulses with ongoing u-oscillations in the
electroencephalography (EEG) alpha-band (8–12Hz) in human sensorimotor cortex results in a differential modulation of corticospinal excitability [32]. To realize
the full potential of TMS to effectively modulate brain networks, each stimulus
must be synchronized with the individual’s instantaneous brain state.
7.2.4.2 Safety
There are no serious adverse events in subjects treated with synchronized EEGTMS.A very small number of subjects reported mild transient discomfort at the site
of stimulation and mild headache lasting until the next day after TMS.These side
effects did not affect the subjects and were fully consistent with the study. No other
side effects were reported.
7.2.4.3 Treatment Regimen
Real-time alpha-synchronized DLPFC stimulation: For brain oscillationsynchronized stimulation of the left DLPFC, the Electroencephalogram(EEG)TMS set-up is used, with the capability of analyzing EEG signals in real-time
and triggering TMS pulses depending on the instantaneous oscillatory phase of
the recorded EEG signal [33]. To synchronize the TMS pulses with the instantaneous oscillatory alpha activity in left DLPFC, the alpha oscillations can be
extracted at the sensor level using a Hjorth Laplace spatial lter centered on the
electrode F5, which is the closest electrode to the target stimulation site and
using four adjacent electrodes. Applying an autoregressive forward prediction
method on the Hjorth-F5 signal led to an accurate prediction of the phase of
instantaneous alpha oscillations, sufcient to trigger the 100 Hz TMS triple
pulses at the predened target phase [33]. In addition, EEG synchronized left
prefrontal TMS for treatment-resistant depression is feasible [34], however, it
has not been validated in OCD.
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7.2.4.4 Clinical Recommendations
Alpha-synchronized rTMS of the left DLPFC is feasible, safe and has specic single-session neuromodulatory effects in patients with antidepressant-resistant MDD.
However, no study has yet claried its effectiveness in OCD.That is why it is
less used in clinical practice compared to rTMS.In future studies, physiological
investigations are necessary to better understand which brain regions and which
brain oscillations may serve as suitable targets for directional modulation in relation
to OCD disorders, and clinical trials with repeated stimulation sessions are necessary to investigate the therapeutic potential and efcacy of brain oscillatory synchronized TMS in OCD as compared to current TMS therapies.
7.2.5 TBS
The recently introduced stimulation protocol, known as Theta Burst Stimulation
(TBS), was rst described by Huang etal. in the context of the human motor cortex
[35]. TBS delivers bursts of pulses at a theta frequency, specically triplets of 50Hz
pulses repeated at a rate of 5Hz, to emulate the brain’s natural rhythmic activity.
Depending on the pattern of stimulation, TBS can have either excitatory or inhibitory effects on neural activity. Intermittent Theta Burst Stimulation (iTBS), characterized by intermittent bursts, induces an excitatory effect, whereas Continuous
TBS (cTBS), which involves uninterrupted pulse delivery, results in an inhibitory
effect [36]. Compared to conventional repetitive Transcranial Magnetic Stimulation
(rTMS), TBS at 50Hz can achieve more pronounced and enduring modulations of
cortical excitability [37].
TBS represents an innovative approach within the realm of TMS.It is characterized by its use of a reduced stimulation intensity, operating at about 70% of the
individual’s motor threshold, in contrast to the 100% typically associated with the
resting motor threshold. Additionally, TBS protocols are notably brief, lasting
approximately 40s, in stark comparison to the 15–20min required for conventional
low-frequency or high-frequency TMS treatments. The advantages of TBS become
evident when considering patient experience. By enabling shorter treatment durations and lower intensity levels, TBS minimizes discomfort and enhances tolerability. This feature positions TBS as a more accessible and agreeable choice for patients
undergoing noninvasive brain stimulation therapies, thereby increasing its clinical
appeal and applicability.
A comprehensive review has assessed the potential of TBS in the treatment of
OCD [38]. Findings from Randomized Controlled Trials (RCTs) [39–45] and various open-label studies [46–48] employing TBS suggest that, for individuals with
OCD, TBS does not provide a clinically meaningful benet over sham stimulation
or traditional rTMS protocols. The active treatment response rates observed in these
studies fall within the range of 16–28%. This lack of superior efcacy could be due
to the fact that some patients may not receive an adequate number of treatment sessions in both TMS and TBS regimens. The FDA-approved guidelines recommend a
minimum of 29 sessions; however, many clinical trials involve only 10–20 sessions.
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This insight underscores the importance of maintenance therapy, where the frequency of TMS treatments can be adjusted over time according to individual patient
responses. While the reviewed OCD trials did not explore or address the potential
for maintenance therapy, it is plausible that nonresponders, partial responders, or
those requiring sustained support could derive signicant benets from ongoing
treatment. Moreover, a randomized controlled trial that compared TBS and rTMS in
treating 45 patients with OCD over a 5-day period revealed a notable difference in
response rates: 60% for TBS versus 31% for rTMS [45]. This nding indicates that,
with continued renement and optimization of treatment protocols, TBS has a
promising outlook for delivering effective therapy, particularly when rapid symptom improvement is crucial. Supported by emerging models and advanced technologies, TBS retains considerable untapped potential for mitigating compulsive
symptoms in OCD patients and may also offer benets for associated comorbidities.
A study involving 20Hz theta burst stimulation (TBS-20Hz) guided by neuronavigation, targeting the bilateral DLPFC and the right orbitofrontal cortex (ROFC), has
been used to treat patients with OCD comorbid with depression and anxiety. Patients
completed the Y-BOCS–Self-Report, the Beck Depression Inventory-II (BDI-II),
and the Beck Anxiety Inventory (BAI) weekly to measure changes in OCD, depressive, and anxiety symptoms, respectively. The neuronavigated TBS-20 Hz was
sequentially applied to the right DLPFC, left DLPFC, and then the ROFC.The
results showed that 64% of patients achieved remission from OCD (Y-BOCS-SR≤14)
after an average treatment duration of 6.1weeks. For MDD, 58% of patients reached
remission (BDI<13) within an average of 4.1weeks, while 62% of patients experienced remission from generalized anxiety disorder/panic disorder (GAD/PD)
(BAI < 8) after an average of 4.3 weeks. The use of neuronavigation-assisted
TBS-20Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC,
signicantly alleviated symptoms of OCD, MDD, and GAD/PD [49]. Moreover,
while pharmacotherapy and psychotherapy are available for treating refractory
OCD, the high likelihood of treatment resistance necessitates the exploration of
alternative approaches. TBS technology offers assistance in modulating the activity
of dysfunctional areas in patients with refractory OCD, particularly targeting the
cortico-striato-thalamo-cortical circuit, to restore a functional level comparable to
what is generally accepted as normal [50].
The efcacy of TBS stems from its ability to modulate neural activity in a targeted manner. TMS, the technology underlying TBS, is a safe, non-painful, and
noninvasive method that inuences brain function by generating electromagnetic
elds that penetrate the scalp and skull to reach the cortex. TBS specically enhances
cortical excitability by emulating the natural θ rhythm of the brain, thereby facilitating synaptic plasticity and neurotransmission [51]. When applied, TBS creates
time-varying pulsed magnetic elds at the scalp level, which can penetrate cortical
tissues to a depth of about 2cm. The subsequent electrophysiological effects are
inuenced by multiple parameters of the magnetic eld, such as the frequency and
pattern of stimulation [52]. TBS treatment protocols are currently classied into
several modes: iTBS, asymmetric intermittent Theta Burst Stimulation (aiTBS),
cTBS, and bilateral TBS. Among these, the two predominant forms utilized in
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contemporary clinical studies are iTBS and cTBS, each designed to elicit distinct
patterns of neural response and therapeutic outcomes.
7.2.5.1 iTBS
iTBS involves the administration of 2-s trains of TBS, delivered at intervals of 8s,
over a span of 192s [totaling 600 pulses] [53].
Efficacy
The therapeutic efcacy of iTBS may be linked to its ability to signicantly enhance
lagged nonlinear coherence (phase synchronization) within the prefrontal regions of
interest, including the ACC, superior frontal gyrus (SFG), and middle frontal gyrus
(MFG), across the beta1, beta2, and theta frequency bands. Moreover, iTBS has
been shown to induce notable changes in long-range connectivity between frontoparietal areas, specically in the theta, alpha1, and beta2 frequency bands, as evidenced by increased lagged linear coherence [41]. A pilot study employing a
randomized crossover design utilized iTBS targeted at the left DLPFC to treat
patients with OCD who had inadequate responses to pharmacotherapy and CBT.The
ndings indicated that iTBS delivered to the left DLPFC was both safe and effective, providing sustained relief from OCD symptoms for up to 3months [41].
Targeting the L-DLPFC with iTBS has proven effective for individuals with treatment-resistant OCD.Additionally, a case report demonstrated that combining rTMS
and iTBS, with targets including the bilateral DLPFC and the SMA, was equally
effective in managing refractory OCD as traditional rTMS treatments [54].
Safety
iTBS, as a specialized form of TMS, can commonly lead to side effects such as
headaches, localized scalp discomfort, paresthesia, facial nerve stimulation, dizziness, somnolence, and the induction of hypomanic episodes. Severe potential acute
adverse reactions, though rare, could include seizures or cognitive disturbances.
However, in the current clinical trials for OCD, no signicant adverse reactions to
iTBS have been noted. Specically, in a study targeting the left dorsolateral prefrontal cortex (L-DLPFC) with iTBS for patients with inadequate responses to pharmacotherapy and CBT, all participants reported no adverse events during or following
the treatment period [41]. Given the limited research on the dose–response relationship in iTBS, it remains uncertain whether higher intensity or more frequent iTBS
sessions, administered at 80% of the RMT or active motor threshold (AMT), provide a superior risk-to-benet prole compared to standard iTBS protocols.
Theoretically, lower-intensity protocols might retain advantageous safety characteristics and warrant further investigation to fully understand their therapeutic potential.
Treatment Regimen
rTMS and TBS protocols are usually calibrated based on the minimal intensity
required to induce a motor response in the motor cortex, referred to as the motor
threshold. This threshold can be established through visual observation or by
employing electromyography. In visual assessment, the motor threshold is
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commonly dened as the lowest stimulation intensity that results in visible movement of the target hand muscle in at least 5 out of 10 attempts. When using electromyography, the resting motor threshold is dened as the lowest intensity that elicits
a motor-evoked potential (MEP) with a peak-to-peak amplitude of at least 50μV in
at least 5 out of 10 trials [55].
For iTBS, a widely used protocol involves delivering bursts of pulses at a frequency of 5Hz, with each burst lasting 2s, followed by an 8-s inter-burst interval.
The entire sequence lasts approximately 3min and comprises 600 pulses. In terms
of target areas, recent clinical research indicates that focusing on the left frontolateral region of the dorsolateral prefrontal cortex (LF-R-DLPFC), the supplementary
motor area, and the L-DLPFC may yield more effective outcomes for the treatment
of OCD [8].
Clinical Recommendations
In general, the application of TMS for treating OCD is advised only after rst-line
and second-line treatments, as well as well-established augmentation strategies,
have been fully explored and found inadequate, similar to the approach taken with
other somatic interventions. The evidence base for TMS in OCD remains limited,
largely because the variability in study designs, target brain regions, treatment durations, and stimulation parameters across double-blind sham-controlled trials has
introduced signicant heterogeneity, complicating the assessment of its true efcacy. Despite these challenges, recent meta-analyses and updated clinical guidelines
have begun to reect more favorable outcomes, indicating a growing recognition of
TMS’s potential in the management of OCD [56].
7.2.5.2 Accelerated iTBS
aiTBS is an expedited form of treatment that involves delivering multiple sessions
within a single day over a brief treatment period, typically spanning just a few days.
Efficacy
To date, there has been no validation of the efcacy of aiTBS interventions specically in patients with OCD.Existing aiTBS interventions have primarily focused on
patients with MDD.In a randomized, double-blind, sham-controlled crossover trial,
45 MDD patients received aiTBS applied to the left DLPFC.In this accelerated
neurostimulation paradigm, the placebo response was associated with reduced perfusion in brain regions linked to higher cognitive processes, leading to a decrease in
suicidal ideation [57]. Moreover, aiTBS has been found to be more effective than
sham stimulation in reducing depressive symptoms in patients with treatmentresistant Bipolar Disorder (BD) [58].
Safety
All existing studies have consistently reported that aiTBS is safe and well-tolerated,
with no serious adverse events noted. The most commonly reported side effects
include fatigue, headaches, and local discomfort at the stimulation site, all of which
are similar in frequency and severity to those observed with conventional rTMS
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protocols. Notably, there have been no reports of seizures or mood switches in
patients undergoing aiTBS treatment.
Treatment Regimen
aiTBS is dened as administering at least three iTBS sessions per day, for a minimum of 4 days per week, with the total stimulation/treatment period lasting
1week [59].
The intensity of aiTBS is typically expressed as a percentage of the individual’s
MT.The MT is the minimum intensity of stimulation required to elicit a visible
muscle contraction in a specic muscle group. The optimal stimulation intensity
may vary depending on the disorder being treated and the individual patient characteristics. Generally, intensities ranging from 80% to 120% of the MT have been
used in clinical studies. However, higher intensities may increase the risk of adverse
effects, while lower intensities may be less effective.
aiTBS typically uses a frequency of 50Hz, which is delivered in bursts of
three pulses at 5Hz. The intermittent nature of the stimulation allows for longer
periods of rest between bursts, reducing the risk of neuronal fatigue and enhancing the therapeutic effect. The frequency of aiTBS may be adjusted based on the
specic disorder and the patient’s response. For example, lower frequencies
may be used in patients with a history of seizures or those at risk of adverse
effects.
The duration of aiTBS treatment sessions can vary depending on the disorder
and the treatment protocol. Generally, sessions last between 10 and 30min. The
total number of treatment sessions may also vary, ranging from a few sessions to
several weeks of daily or weekly treatments.
The number of treatment sequences refers to the number of times the stimulation
is delivered in a single session. Multiple sequences may be used to increase the total
amount of stimulation and enhance the therapeutic effect. However, the optimal
number of sequences may vary depending on the disorder and the patient’s tolerance. Generally, two to four sequences are used in clinical studies, with a rest period
of a few minutes between sequences.
Clinical Recommendations
Considering the current paucity of research on aiTBS interventions for OCD, there
is a critical need for more clinical evidence to support its use in this patient population. Given the accessibility and potential benets of aiTBS, it is feasible to consider aiTBS as an adjunctive therapy and as a supplementary treatment option when
standard pharmacological or psychological treatments have not been effective. This
approach could provide valuable alternatives for patients with refractory OCD,
enhancing the therapeutic arsenal available to clinicians.
7.2.5.3 Continuation TBS
cTBS is a form of rTMS that exerts faster and more enduring effects on synaptic
plasticity compared to conventional rTMS. cTBS involves the uninterrupted administration of TBS for 40s, which also totals 600 pulses [53].
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Efficacy
Overall, cTBS has demonstrated notable efcacy in improving obsessive symptoms. Compared to iTBS, cTBS exhibits more signicant short-term benets in
reducing these symptoms. In a randomized double-blind study involving 69 patients
with OCD, both iTBS and cTBS were applied to the left OFC using 600 pulses at
110% of the resting motor threshold. The study found that both forms of TBS modulated OFC activation as expected. However, cTBS showed a more pronounced
benecial effect on the acute laboratory assessment of compulsive behaviors 90min
after stimulation, compared to iTBS.Importantly, these acute behavioral improvements persisted for up to 1week following cTBS treatment [60].
Furthermore, cTBS administered using an accelerated protocol has shown more
pronounced therapeutic effects in treating OCD.A study included 32 OCD patients
who were randomly assigned to either active or sham cTBS groups. In the active
cTBS group, an accelerated protocol was employed, involving bursts of three stimuli repeated at 5Hz, with each burst delivered at 50Hz and 80% of the motor threshold (MT). Participants underwent two sessions per day, each session consisting of
900 pulses, totaling 30 sessions over 3weeks (10 sessions per week). The ndings
revealed that adjunctive accelerated cTBS led to signicant improvements in psychopathology, disease severity, and depressive symptoms among OCD patients
[44]. Compared to traditional 1-Hz rTMS, the accelerated high-dose Theta Burst
Stimulation (ahTBS) protocol did not show a signicant difference in clinical effectiveness after 5days of treatment. Both groups experienced signicant reductions in
Y-BOCS scores, and there were no statistically signicant differences in secondary
outcomes, such as depressive symptoms, anxiety symptoms, and response rates,
indicating the non-inferiority of ahTBS.However, a trend toward a higher response
rate was observed in the ahTBS group. Neuropsychological testing showed that
neither treatment led to adverse cognitive side effects. These results suggest that
accelerated high-dose TBS is equally safe for treating OCD and demonstrates comparable short-term efcacy to traditional 1-Hz rTMS [45]. In a study involving
OCD participants, an intensied novel cTBS protocol targeting the orbitofrontal
cortex (OFC) was administered. Patients received 10 sessions of cTBS, with two
sessions per day (a total of 1200 pulses per day; intensive protocol), 5days per
week. Signicant group-by-time effects were observed for obsessions, compulsions, HAMA, HAMD, and CGI scores at baseline, immediately after the last treatment, and 2 weeks posttreatment. However, when controlling for confounding
variables, only the HAMA scores and CGI effects remained statistically signicant.
We conclude that intensied OFC cTBS in OCD is well-tolerated and results in
clinically meaningful improvements in anxiety symptoms and overall severity. This
improvement in anxiety symptoms may be due to the modulation of state-dependent
dysregulation in OCD [40].
In the context of treatment-resistant OCD, the efcacy of cTBS appears to be
somewhat limited. Meta-analyses have indicated that, for cTBS, there were no signicant differences in Y-BOCS scores or clinical response rates between the active
stimulation group and the sham group. A reasonable explanation for this nding is
that the three TBS studies utilized a stimulation intensity of 70% or 80% of the
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RMT, delivering 600 pulses per session, which may be insufcient to achieve therapeutic benets in patients with treatment-resistant OCD [61]. Furthermore, a foundational study investigated whether modulating activity in the right OFC using
cTBS could impact symptoms of OCD.In this study, 28 participants with treatmentresistant OCD were randomized in a double-blind manner to receive either active or
sham cTBS targeting the OFC, administered twice daily for 5days a week over a
2-week period. The Y-BOCS was used to assess clinical response to the treatment.
Following the two-week treatment period, there were no statistically signicant differences between the groups in Y-BOCS scores or other secondary outcomes, such
as anxiety symptoms and response rates. While the active group demonstrated a
signicant improvement in depressive symptoms, this difference was not sustained
and became nonsignicant by the 6-week follow-up. These results suggest that
although cTBS targeting the right OFC is safe for treating symptoms of treatmentresistant OCD, a two-week treatment duration may be insufcient to achieve a clinically signicant effect [43]. Researchers evaluated the therapeutic efcacy and
tolerability of cTBS applied to the SMA in patients with treatment-resistant
OCD.Thirty outpatient participants with treatment-resistant OCD were randomly
assigned to receive either active cTBS or sham cTBS for 6weeks (ve times per
week). Each treatment session consisted of 600 stimuli delivered at 70% of the resting motor threshold. Patients were assessed at baseline, at the end of treatment
(Week 6), and at follow-up (Week 12). A response to treatment was dened as a
reduction of at least 25% on the Y-BOCS.The results showed no statistically signicant differences in treatment effects between the active cTBS group and the sham
cTBS group. There were no differences in response rates at Week 6 and Week 12.
Both groups exhibited similar improvements in depressive and anxiety symptoms.
Overall, cTBS was found to be safe but did not signicantly improve symptoms in
patients with treatment-resistant OCD.Further research is needed to determine the
optimal parameters for cTBS in treating OCD [39].
Safety
As a variant of TBS, cTBS typically presents with side effects that are similar to
those associated with TBS and other forms of rTMS.Common side effects may
include mild to moderate headaches, discomfort or pain at the stimulation site, muscle twitching or tremors, transient mood changes such as anxiety or emotional uctuations, temporary hearing loss or tinnitus, and, in extremely rare cases, seizure
induction, especially in individuals with a history of epilepsy. These side effects are
generally temporary and subside soon after the end of the treatment session. In very
rare instances, more serious side effects such as severe mood disturbances or cognitive impairments could potentially occur, although these are highly uncommon. To
date, studies on cTBS in patients with OCD have not reported any such severe
adverse reactions. The side effects observed in these studies have been limited to the
milder, more common types mentioned above, indicating that cTBS is generally
well-tolerated in this patient population.
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Treatment Regimen
Current cTBS treatments for OCD predominantly focus on the DLPFC and the
SMA.The DLPFC is among the most frequently targeted regions in OCD therapy
due to its involvement in cognitive control and emotional regulation. Stimulating
the DLPFC can enhance patients’ ability to manage obsessive thoughts and reduce
compulsive behaviors. The SMA, which plays a key role in motor control and
behavioral planning, is another important target. Stimulation of the SMA can help
mitigate motor-related compulsions, such as repetitive movements or rituals, which
are common in OCD.Beyond the DLPFC and SMA, some research has also investigated other brain areas as potential targets for stimulation, including the OFC and
the ACC.However, the effectiveness of these alternative targets remains to be fully
validated through additional research.
The intensity of cTBS is typically expressed as a percentage of the stimulator’s
output. Currently, there is no consensus on the optimal stimulation intensity for
treating OCD with cTBS.Generally, the stimulation intensity ranges between 80%
and 120% of the RMT.Higher stimulation intensities may enhance treatment efcacy but can also increase the risk of adverse reactions. Some studies have identied
85% RMT as an effective stimulation intensity, gradually escalating to 115% RMT
during the intervention period [60]. The stimulation frequency of continuous Theta
Burst Stimulation (cTBS) is typically set at 50Hz. However, some studies have also
explored the impact of different stimulation frequencies on the treatment of
OCD.The duration of cTBS stimulation is usually 40 s. During this period, the
stimulator delivers magnetic pulses at a specied frequency and intensity. Shorter
stimulation durations may reduce treatment efcacy, while longer durations could
increase the risk of adverse reactions. Therefore, when determining the stimulation
duration, it is important to balance the patient’s tolerance with the desired treatment
outcome. The number of treatment sessions for using cTBS to treat OCD typically
ranges from 10 to 20 sessions. Treatments are generally administered 3 to 5 times
per week over a period of 2 to 4weeks.
Some enhanced protocols for cTBS intensify the intervention frequency by using
a stimulation intensity of 80% MT, delivered continuously in triplets at a 50Hz
frequency, and repeated at a 5Hz frequency. Treatments are administered twice
daily, with each session consisting of 900 pulses, and at least a 5-hour interval
between sessions. The total number of treatments is 30, with sessions spaced over
3weeks. This treatment regimen, which involves more than 1000 pulses per day for
over 2weeks, is referred to as an “accelerated protocol”[44]. Another modied
accelerated high-dose theta burst stimulation protocol has a total intervention duration of 5 consecutive days. Each session of the modied continuous TBS consists of
1800 pulses, with each set of pulses comprising 600 theta bursts. Each theta burst is
made up of 3 pulses at 50Hz, and these theta bursts are repeated at a frequency of
5Hz. Treatment is administered 10 times per day, with each session spaced 50min
apart. The stimulation intensity is set at 80% of the resting motor threshold
(RMT) [62].
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Clinical Recommendations
Overall, compared to other TBS paradigms, cTBS has been studied more extensively in the context of OCD.However, due to the heterogeneity of parameters and
targets used in these studies, it is not yet conclusive whether cTBS effectively
improves OCD symptoms. Nonetheless, cTBS and its intensied protocols still hold
signicant clinical potential. More precise neuro-navigation and more specic treatment targets remain key focuses for future research.
7.2.5.4 Bilateral TBS
Bilateral TBS involves the simultaneous application of TBS to both sides of the
brain. This method of stimulation can more effectively induce plasticity changes in
neurons. It works by inuencing the balance between long-term potentiation and
long-term depression.
Efficacy
The SMA is a commonly used target in bilateral TBS treatment for patients with
OCD.A study administered 20 consecutive sessions of bilateral cTBS to the SMA
in 29 patients with OCD and 29 healthy controls. The results showed that 11 out of
the 29 patients (37.93%) responded to the bilateral cTBS, with signicant clinical
symptom relief observed in the OCD patients following the bilateral SMA cTBS
treatment. Additionally, the functional connectivity between the Cerebelum_
Crus2_L and Frontal_Inf_Tri_L in OCD patients indicated a favorable prognosis
for cTBS efcacy. No serious adverse events occurred in any of the patients.
Intervention with bilateral SMA cTBS can signicantly improve symptoms in moderate to severe medication-refractory OCD patients. Pretreatment functional connectivity may serve as a valuable potential predictor of treatment outcomes [46]. In
a single-blind, sham-controlled design of cTBS applied to the bilateral SMA for
patients with OCD, 54 OCD patients were randomly assigned to receive either
active or sham cTBS treatment over the bilateral SMA for 4weeks (5 times per
week, totaling 20 sessions). Patients were evaluated at baseline (week 0), end of
treatment (week 4), and follow-up (week 8). The results showed no signicant difference in the treatment response rate between the fourth and eighth weeks. At week
4, there was a signicant difference in improvements in depression and anxiety
between the two groups. There were no signicant differences in treatment satisfaction and dropout rates between the groups. Bilateral SMA cTBS treatment was
found to be safe and tolerable, signicantly improving depression and anxiety in
OCD patients, but it was not sufcient to improve OCD symptoms [8]. For some
OCD patients who respond poorly to medication, open-label case reports have indicated that bilateral cTBS targeting the MA may alleviate obsessive symptoms in
patients with OCD [47].
Furthermore, combining iTBS and cTBS to target the DLPFC may offer an
effective treatment option for perinatal OCD.This approach can help address practical clinical issues such as medication safety for breastfeeding mothers and the specic needs of this population. A clinical case report of a dual-stimulation protocol
using both iTBS and cTBS for postpartum OCD provides evidence that this