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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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Treatment Regimen
For unilateral applications, the amplitude could remain constant for both cTBS and
TBS-DBS; however, slight adjustments are necessary for bilateral TBS-DBS to
align with observed effects and side effects. Safety and tolerability of TBS-DBS are
clinically evaluated by clinicians during a prior monopolar review, which involved
assessing side effect thresholds (including dysarthria, paresthesia, tetanic contractions, or malaise) and gathering feedback from subjects regarding any side effects
experienced during the 30-min DBS session [149].
Previous studies have utilized treatment regimens involving bilateral
TBS. Patients will be randomly assigned to two treatment arms in a 1:1 ratio.
Randomized patients will receive a total of 15 sessions of either bilateral TBS or
sham stimulation (placebo) during a treatment period of 3 consecutive weeks (1
session per weekday). In each session, stimulation (or sham stimulation) will be
applied successively to the left and right temporoparietal cortex, or vice versa. To
control for order effects, the stimulation sequence (left–right/right–left) will be randomized in the rst session and reversed in each subsequent session [148]. Results
indicated a reduction in the mean PSYRATS-AH score following bilateral TBS
compared to sham treatment.
Another study reported the use of bilateral cTBS over the temporoparietal
cortex in a 52-year-old man, administered daily for 9weeks, which resulted in
the suppression of AVH. The patient had a longstanding history of paranoid
schizophrenia. The stimulation was delivered at 80% of the AMT, targeting the
TPJ between the P3/T3 and P4/T4 electrodes based on the 10–20 EEG system.
Each cTBS session consisted of a continuous 40-s train, with each burst comprising three pulses at 50Hz. While a reduction in AVH was observed during the
early sessions, complete attenuation of AVH was noted by the sixth week of
treatment [95].
Clinical Recommendations
Each bilateral TBS session consisted of a continuous 40-s train, with each burst
comprising three pulses at 50Hz. Further research and consensus are needed on the
levels of clinical recommendation for bilateral TBS (Table5.1).
5.2.6 MST
Magnetic seizure therapy (MST) presents a promising alternative to electroconvulsive therapy (ECT) [150]. To address the inherent limitations of electrical stimuli,
the concept of using magnetic pulses as substitutes for ECT was proposed in
1994 [150].
MST is a noninvasive physical treatment developed as an enhancement over conventional convulsive therapies [151]. It integrates the characteristics of both ECT
and rTMS.MST generates electromagnetic stimulation through rapidly alternating
magnetic elds, similar to rTMS, but with greater intensity [151] This stimulation
induces a seizure to alleviate symptoms [152]. One notable advantage of magnetic
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stimuli is their ability to penetrate the scalp and skull without resistance, facilitating
targeted application to supercial cortical regions, which may help minimize cognitive side effects [150].
MST is administered under general anesthesia, requiring short-acting anesthetics
and muscle relaxants [151, 153]. A twin coil positioned at the vertex (or, in some
cases, a gure-eight coil over the right prefrontal cortex) generates magnetic elds
that create an indirect electric current in the brain, inducing a seizure when it surpasses the individual seizure threshold [154–157].
The magnetic seizure threshold is typically titrated during the rst treatment session by progressively increasing the duration of the train [154]. EEGs are monitored
and assessed to ensure the occurrence of the required seizure [156], and precautions
are taken to prevent side effects. Earplugs are provided for both patients and staff to
prevent tinnitus or potential hearing damage [154], and patients are tted with a bite
block to protect their teeth [158]. Session arrangements generally mirror those of an
ECT treatment plan, occurring twice a week for a duration of 5–6weeks [157, 158].
MST was rst employed in a study aimed at treating a patient with major depression in 2001 [159]. Since then, a growing number of studies have investigated the
antidepressant effects of MST for depression, yielding promising results [154],
although these ndings remain somewhat unclear [160]. However, evidence regarding its efcacy for schizophrenia is limited. It remains uncertain whether MST is
more or less effective than ECT or nonconvulsive TMS for schizophrenia, as well as
whether MST offers additional benets for individuals with this condition.
Schizophrenia is one of the most prevalent and debilitating mental disorders.
Approximately 20% of individuals with schizophrenia do not respond to antipsychotics, which currently serve as the primary treatment for this condition, necessitating the exploration of alternative treatment options. MST is one of the novel
NIBS techniques that have been investigated in recent years [152].
Pilot studies have indicated that MST is safe for individuals with schizophrenia
[161]. Additionally, because it may result in less cognitive impairment, MST could
be particularly valuable for older populations [162].
The research also found that MST, when compared to ECT, may lead to fewer
delayed memory decits and less cognitive deterioration (as measured by the number of individuals with delayed memory decits and the mean change in global
cognitive function). Furthermore, MST may enhance cognitive function to a greater
extent (as indicated by the number of individuals showing any cognitive improvement) [152]. Researchers have also discovered that MST and ECT may be comparable in improving the overall condition of individuals with schizophrenia, as well
as in alleviating both positive and negative symptoms of the disorder [152].
5.2.6.1 Efficacy
MST is an innovative neurotherapeutic intervention currently under development
for treating major affective disorders. It has been designed as a more targeted form
of convulsive therapy, specically inducing seizures in the prefrontal cortex while
sparing medial temporal structures such as the hippocampus [156, 159, 163–165].
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This novel approach seeks to combine the effectiveness of ECT with the minimal
cognitive side effects associated with rTMS [166].
MST functions by inducing therapeutic seizures using HF-rTMS [167, 168].
Clinical evidence suggests that it offers signicant benets, particularly in reducing
neurocognitive adverse effects, making it a promising alternative to ECT [169]. The
treatment has demonstrated response rates ranging from 40% to 70%, with remission rates between 15% and 46% [170]. Preliminary evidence also points to potential antipsychotic effects of MST in schizophrenia, with negligible neurocognitive
adverse effects.
MST and ECT may be comparable in enhancing the overall condition of adults
with schizophrenia, as well as in alleviating both positive and negative symptoms.
Notably, MST may result in fewer delayed memory decits and less cognitive deterioration while also improving cognitive function compared to ECT.
A systematic review synthesized two single-arm self-controlled studies and
found low certainty of evidence, suggesting that MST improved psychotic symptoms, albeit with a high discontinuation rate. The review also reported inconsistent
evidence regarding the cognitive adverse effects of MST.This aligns with our ndings, highlighting the current lack of high-quality evidence investigating the effects
of MST in individuals with schizophrenia [171].
As a novel NIBS technique, MST was developed as an alternative to existing
treatment options for schizophrenia. However, no recommendations for this new
therapy can be made until a thorough assessment is conducted. The available
data are too scarce to draw meaningful conclusions for individuals with schizophrenia, clinicians, and policymakers. Those considering MST should remain
aware of the unknown risks involved, and caution should be exercised before its
application [152].
Further investigation is essential to address these questions with certainty, with
particular emphasis on evaluating cognitive function in relation to the side effects
prole.
Despite the limited data, current evidence does not rule out the potential for MST
to serve as a promising treatment alternative, potentially offering desirable efcacy
and a benign side effect prole for individuals with schizophrenia. Well-designed
RCTs are needed to inform clinical practice regarding the efcacy and tolerability
of MST in this population. The optimal information size should be achieved to
ensure good precision, and efforts should be made to implement blinding to
avoid bias.
5.2.6.2 Safety
Research on the neurocognitive effects of magnetic seizure therapy consistently
indicates that it is a cognitively safe neurotherapeutic intervention. Animal studies
have demonstrated that MST does not lead to cognitive dysfunction [172, 173] or
induce pathological changes in the brain [174, 175]. Furthermore, both preclinical
and clinical evidence support the conclusion that MST does not adversely affect
neurocognitive functions [176]. Additionally, pilot studies have shown that MST is
safe for individuals with schizophrenia [161].
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A convergence of ndings from virtual computer simulations, preclinical studies, and clinical investigations reveals that MST has a negligible impact on cortical
and subcortical structures, thereby helping to preserve cognitive abilities. Data from
virtual models show that MST stimulation inuences only 21% of total brain volume, with effects conned to gray matter. Preclinical studies further reinforce this
notion, indicating that even at suprathreshold levels, MST has minimal effects on
cortical areas and cognitive functions. These results are echoed in clinical trials,
providing a robust foundation for the safety of MST across various research methodologies [166].
In terms of adverse events, no signicant complications were identied. The
most frequently reported adverse drug reactions (ADRs) included dizziness and
subjective memory loss [176].
5.2.6.3 Treatment Regimen
MST employs a TMS device along with specialized coils to deliver a series of magnetic
pulses at intensities sufcient to induce a seizure while the patient is under general anesthesia. Key parameters that can be adjusted in MST include the conguration and placement of the magnetic coil, as well as specic characteristics of the magnetic pulse, such
as frequency, pulse width, amplitude, duration, and dosage (threshold or suprathreshold). Similar to ECT, these parameters are essential for optimizing the balance between
therapeutic efcacy and adverse effects. For example, ECT administered with right unilateral electrode placement, ultra-brief pulse widths, and titrated doses has demonstrated
high efcacy with minimal cognitive side effects compared to other congurations
[177]. A recent review by Hoy and Fitzgerald (2010) highlighted that MST parameters
signicantly inuence treatment outcomes, noting that seizure induction is more reliable
at 100Hz than at 50Hz [155].
The MST setting is designed to closely mirror ECT clinical practices in China
[178]. Participants in the study were scheduled for 10 sessions of MST over a
4-week period, consisting of 3 sessions per week during the rst 2weeks and 2sessions per week in the following weeks. MST was administered under general anesthesia using intravenous etomidate (0.21–0.3mg/kg) and propofol (1.82–2.44mg/
kg) for sedation. Muscle relaxation was achieved with intravenous succinylcholine
(1mg/kg), and intravenous atropine (0.5mg) was administered to reduce airway
secretions. The procedure utilized a MagPro X100 (MagVenture A/S, Denmark) set
to 25Hz and 100% output, with a pulse width of 370 us and a peak magnetic eld
intensity of 4.2 Tesla.
To account for the likelihood that seizure thresholds may increase with ongoing treatment [179], a titration method was employed to determine the duration of magnetic
stimulation. The initial duration began at 4s and was increased by 4s in each subsequent
session, up to a maximum of 20s (corresponding to 100–500 pulses per session). If the
quality of the seizure was deemed inadequate (dened as a duration of less than 15s)
during a session, the duration increment for the next session would be adjusted to 8s. In
instances where no seizure was induced, an additional stimulation lasting 20 s was
administered immediately. The magnetic stimulation was delivered via a twin coil
5 Schizophrenia
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positioned with its midline on the vertex, allowing for the induction of a stronger and
deeper electric eld compared to other MST coil congurations [150].
In the other study, participants were placed under general anesthesia using intravenous etomidate and propofol. Intravenous succinylcholine was administered as a
muscle relaxant, while intravenous atropine was used to reduce airway secretions.
MST was delivered at a frequency of 50Hz and 100% output, with a pulse width of
370 us and a peak magnetic eld intensity of 4.2 Tesla. The duration of stimulation
was titrated for each participant based on the quality of the induced seizure, with a
maximum duration of 20s. If no seizures were generated, an additional stimulation
lasting 20s was administered immediately. Magnetic stimulation was delivered via
a twin coil positioned with its midline on the verte [152]. The ndings suggest that
MST and ECT may be comparable in enhancing the overall condition of adults with
schizophrenia, as well as in alleviating both positive and negative symptoms.
Additionally, MST may result in fewer delayed memory decits and less cognitive
deterioration while improving cognitive function compared to ECT.There appeared
to be no signicant difference between the two groups regarding early study termination due to any reason, adverse effects, or perceived inefcacy.
5.2.6.4 Clinical Recommendations
The ndings indicate that improving seizure quality and treatment response may be
possible by employing higher magnetic pulse dosages and frequencies. Nevertheless,
further research is needed to explore the impact of frequency, treatment frequency,
and other parameters on cognitive functioning [150]. The levels of clinical recommendation for MST require further investigation and consensus (Table5.1).
5.3 tDCS
Nearly 15years ago, researchers revitalized a eld of study examining the effects of
applying a weak electric current between two electrodes placed on the scalps of
healthy individuals [180]. This technique, termed transcranial direct current stimulation, demonstrated a signicant, time-dependent, and polarity-specic modulation
of neuronal populations beneath the electrodes. Since this initial neurophysiological
discovery, an increasing number of researchers and clinicians have been investigating the effects of tDCS across various cognitive and behavioral domains [181].
Modern tDCS devices typically consist of an adjustable direct current stimulator
and two stimulating electrodes (an anode and a cathode). These electrodes are usually attached to two distinct locations on the scalp—either directly or via larger
sponge electrodes and a weak current (0.5–2.0mA) is passed between them. As
these current ows between the electrodes, it is believed that a small portion of it
penetrates the brain. This current ow is thought to modulate neural activity beneath
the electrode and, to a lesser extent, inuence diffuse areas of the brain [181–183].
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H. Deng et al.
5.3.1 Conventional tDCS
5.3.1.1 Efficacy
As a novel neuromodulation technique, tDCS has been used extensively in the treatment of schizophrenia. Active conventional tDCS signicantly reduced symptom
severity compared to baseline and compared to sham conventional tDCS in patients
with schizophrenia [184]. Although accumulating evidence indicates that tDCS has
not demonstrated effectiveness in diminishing overall positive symptoms in patients
with schizophrenia, a meta-analysis revealed that active tDCS with ≥10 stimulation
sessions could signicantly improve auditory hallucinations compared to sham
[185]. However, conventional tDCS protocols have exhibited a notable enhancement in negative symptoms, yielding a medium effect size. Furthermore, there is
substantial evidence supporting the use of conventional tDCS in enhancing attention and working memory in patients with schizophrenia [5, 186]. Additionally,
emerging studies suggest that conventional tDCS may be efcacious in improving
attention and vigilance [187].
5.3.1.2 Safety
The general impression is that conventional tDCS is a safe technique, with adverse
effects that are mild and transient [188]. A meta-analysis by Brunoni and colleagues
[189] showed that conventional tDCS has a benign side-effect prole when administered in 1–2 sessions to healthy volunteers. However, only 56% of all reviewed
studies reported the presence or absence of adverse effects, indicating an underreporting of adverse effects in conventional tDCS clinical research. According to this
meta-analysis, the most common adverse effects are observed in the active group,
including itching, tingling, headache, burning sensation, and discomfort. While
conventional tDCS has been well studied in adults, there is currently no specic
guidance on conventional tDCS dosage for children. Limited studies of conventional tDCS in the pediatric population have shown that adverse effects are similar
to those in adults, primarily limited to itching or tingling at the site of stimulation,
with no reports of serious side effects [190]. One study showed that 10sessions of
conventional tDCS were well tolerated, with the most common side effect being
irritability, followed by acute mood changes, tingling and itching [191]. However,
due to anatomical and neurophysiological differences in the developing brain, dosage parameters considered safe and effective in adults should be adapted to achieve
comparable results in children [192]. The researchers underscored the importance
of exercising caution when employing current intensities of 2mA or higher in pediatric populations, as the average current dose over the cortical surface following
conventional tDCS stimulation may be higher in children than in adults.
5.3.1.3 Treatment Regimen
The most common cortical targets in schizophrenia are the left DLPFC and the left
TPJ.Dysfunctional activation of the prefrontal cortex has been associated with negative symptoms and cognitive decits [193], while auditory hallucinations are
thought to stem from spontaneous hyperactivity in temporal regions that is not
5 Schizophrenia
Table 5.2 Optimization strategies of tDCS in schizophrenia
tDCS Clinical recommendations Levels+references
Cathode
Anode position
Conventional
tDCS
HD-tDCS F3 Unclear 2mA
Abbreviations: HD-tDCS high-denition transcranial direct current stimulation, N/A not applicable, tDCS transcranial direct current stimulation
The midpoint
between the
anode-F3 and
FP1
position
The midpoint
between the
cathode-T7
and P3
Intensity
(mA)
≥0.515 ≥20
Length
(min)
≥20 ≥5
Duration
(sessions)
10–40 Second-line [7,
195, 198–212]
N/A [195, 211,
213–216]
127
sufciently regulated by reduced prefrontal activity [186, 194]. Typically, conventional tDCS protocols position the anode to increase neural activity in the left
DLPFC and the cathode to decrease neural activity in the left TPJ, enabling the
simultaneous targeting of negative symptoms and hallucinations [186, 195–198].
Brain stimulation with conventional tDCS involves the application of weak electric
elds at currents of 1–2mA for 20–30min. The recommended treatment regimen
typically involves between 10 and 40sessions. Ultimately, it appears that conventional tDCS may offer potential benets for alleviating negative symptoms in
patients with schizophrenia.
5.3.1.4 Clinical Recommendations
Conventional tDCS for schizophrenia recommends stimulating the midpoint
between the anode-F3 and FP1 and the midpoint between the cathode-T7 and P3.
The current density used was 0.515A/m2 for 20min for 10–40 treatments, with
great potential to improve hallucinatory symptoms (level B evidence). Table 5.2
summarizes the optimization strategies for this treatment regimen.
5.3.2 HD-tDCS
High-denition transcranial direct current stimulation (HD-tDCS), an optimized
form of tDCS, has the potential for more focused neuromodulation [217].
A notable challenge of conventional tDCS is its use of large electrodes positioned far apart, which leads to the stimulation of both the targeted region and adjacent structures [218]. To overcome this limitation, a more focused technique has
been developed called HD-tDCS.This approach employs a 4*1 ring electrode conguration that effectively narrows the area of stimulation, enhancing the precision
and effectiveness of the treatment [219].
HD-tDCS is grounded in the technical methodology of conventional tDCS but
offers a more precise, focused, and longer-lasting effect [220].
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H. Deng et al.
5.3.2.1 Efficacy
HD-tDCS represents an advancement over conventional tDCS, offering the potential for precise and focused neuromodulation. HD-tDCS employs arrays of small
electrodes (12mm), and utilizing these electrodes in a 4*1 ring conguration is
predicted to concentrate stimulation based on nite element model analyses derived
from high-resolution magnetic resonance imaging. Studies have demonstrated that
conventional tDCS montages induce diffuse distributions of current ow across
widespread brain areas, where the highest current density may not occur directly
beneath the electrodes. In contrast, HD-tDCS ensures elevated current densities primarily in the target area, resulting in effects that appear stronger, last longer, and are
more focused than those of conventional tDCS [221, 222].
HD-tDCS represents a cutting-edge NIBS technique based on the principle that
weak electric currents, when precisely directed at specic areas of the scalp, can
stimulate the underlying cortical regions. While HD-tDCS shares a fundamental
technical framework with conventional tDCS—utilizing a montage that consists of
one anode and one cathode—it incorporates several modications that enhance its
focus and prolong the neuromodulation effects [223].
Similar to conventional tDCS, which establishes a unidirectional circuit through
the placement of electrodes on the scalp, HD-tDCS also utilizes an anode and a
cathode. However, its key advantage lies in the targeted delivery of current to the
desired site. Among various montage congurations, the 4*1 ring montage is the
most frequently employed, allowing HD-tDCS to achieve specic therapeutic
effects while minimizing the inuence of cortical stimulation from opposing polarities [219, 223]. HD-tDCS is designed to provide more precise cortical stimulation
or inhibition, along with improved cortical penetration due to its unique montage
design, which confers notable advantages.
The clinical utility of HD-tDCS has been validated in various settings [224].
Three open-label studies involving larger sample sizes have investigated its efcacy
across psychiatric disorders, including schizophrenia [225], depression [226], and
post-traumatic stress disorder (PTSD). Together, these studies provide independent
evidence supporting the clinical effectiveness of HD-tDCS [227].
Currently, while in psychiatric contexts, it has primarily focused on treating
auditory hallucinations [227]. Recent studies have indicated the potential utility of
HD-tDCS in treating tinnitus [228] and auditory hallucinations in schizophrenia
[225]. However, we did not nd any published research on the application of
HD-tDCS for the treatment of negative symptoms in schizophrenia [217].
Compared to healthy controls, individuals with schizophrenia exhibit reduced
integrity of the white matter tracts in the corpus callosum and corona radiata.
HD-tDCS has been shown to enhance integrity in the corpus callosum as well as the
anterior and superior corona radiata, which correlates with improvements in cognitive performance. Thus, HD-tDCS presents a promising approach to ameliorate
cognitive decits in schizophrenia through its modulatory effects on white matter
tracts. Given the lack of approved treatments for cognitive decits, these ndings
hold signicant clinical relevance [220].
5 Schizophrenia
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5.3.2.2 Safety
Research indicates that HD-tDCS is both safe and well-tolerated at current intensities of up to 2mA [229]. Adverse effects were measured using the checklist developed by Eryilmaz etal. [230]. Itching at the stimulation site was reported by two
patients in a total of 3 sessions. Burning sensation at the stimulation site was
reported by one patient during a session. All these adverse effects were reported by
patients receiving active stimulation. However, both itching and burning sensation
were short lasting, and none of those adverse effects warranted discontinuation of
HD-tDCS sessions. No other adverse effects were noted [217].
5.3.2.3 Treatment Regimen
HD-tDCS was administered using the Starstim 32 device (Neuroelectrics BE,
Spain). Starstim 32 is a wearable device that wirelessly transmits 32-channel data
via Wi-Fi. The study utilized a 4*1 ring montage with NG Pistim electrodes, which
are sintered Ag/AgCl ring electrodes with a 1cm radius. Electrodes were arranged
on the scalp with the assistance of an electroencephalogram (EEG) cap and a plastic
casing to secure their positions. The central electrode, designated as the anode, was
placed at F3 (left DLPFC) according to the 10/10 montage of the EEG electrode
placement system. This electrode was surrounded by four return electrodes (FC1,
F7, FC5, and AF3), dening the modulation area. All sessions were monitored for
adverse effects, and at the end of each session, the HD-tDCS adverse effect checklist was applied [230]. In line with previous studies, the stimulation level for the
active group was set at 2mA, with 2sessions administered each day for 5 days,
featuring a 3-s ramp-up and ramp-down. The total stimulation duration was 20min
[195, 231]. Two consecutive sessions were separated by a minimum interval of 5h.
For the sham stimulation, electrodes were positioned identically to those in the
active stimulation, but a 1mA direct current was applied with a 3s ramp-up and
ramp-down for 30s [232], providing a sensation of stimulation while minimizing
actual effects. Allocation to the active or sham group was conducted through envelope randomization [217].
In a case of persistent AVH in schizophrenia with comorbid alopecia universalis,
central cathodal stimulation was applied to CP5 (temporoparietal junction, TPJ)
using the 10/10 EEG system, with four return electrodes at FT7, FC3, PO7, and P1.
The stimulation was set at 2mA for a 20-min session, with a 3-h intersession interval over 5days, totaling 10sessions. Remarkably, there was a complete alleviation
of auditory hallucinations following 5days of HD-tDCS treatment [227]. No electrode-based side effects were noted, despite the absence of scalp hair due to comorbid alopecia universalis [227].
In another open-label study involving 19 participants with persistent AVH in
schizophrenia, central cathodal stimulation was again directed to CP5 (TPJ) using
the 10/10 EEG system and four return electrodes at FT7, FC3, PO7, and P1. This
study reported a signicant reduction in auditory hallucinations after 5 days of
HD-tDCS treatment [225].
Persistent AVH in schizophrenia case report central cathodal stimulation to CP5
(TPJ) employing the 10/10 EEG system, with four return electrodes positioned at
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H. Deng et al.
FT7, C5, CP3, and P5. The intervention led to a signicant reduction in auditory
hallucinations following 5days of HD-tDCS treatment, utilizing a 2mA current for
20-min sessions, with a 3-h intersession interval across 10sessions [227].
In a previous study, the intervention employed a 4*1 HD-tDCS device (Soterix
Medical Inc., USA). Dedicated Soterix software (HD-Targets and HD-Explore™)
was utilized to congure electrode montages and map electrical elds, allowing for
the maximization of stimulation in the target area [233]. Specically, a 4*1 ring
conguration was implemented, featuring one central anodal electrode surrounded
by four return cathodal electrodes. The anode was positioned over the left DLPFC
at F3 (10/20 EEG system), with the four cathodes placed at AF3, F5, F1, and FC3,
forming a circular arrangement. This HD-tDCS montage is widely employed to
target the left DLPFC in neuropsychiatric disorders [227]. Conductive gel was carefully applied to each individual electrode. Subsequently, the electrodes were rmly
afxed to the scalp by means of an electroencephalogram (EEG) cap. Before the
initiation of stimulation and throughout every session, impedance monitoring of the
interface between the electrodes and the scalp was meticulously carried out.
In the active group, a consistent 2mA current was administered for a duration of
20min. In contrast, in the sham group, the same current was delivered for merely
30s. It is worth noting that for both groups, there were 20-s “ramp up” and “ramp
down” periods incorporated. Participants were explicitly instructed to maintain a
state of relaxation and to refrain from engaging in any form of activity during the
entire stimulation period [220].
In other study, participant received 10 sessions of HD-tDCS at 2 mA for
20 min, administered twice daily over 5 days. The improvement in negative
symptoms within the active group was statistically signicant, with a p-value of
0.05 when compared to the sham group. These results suggest that HD-tDCS
may contribute to the improvement of negative symptoms in schizophrenia, indicating that its use as an adjunct to pharmacological treatment for these symptoms
may be worth considering [217].
5.3.2.4 Clinical Recommendations
Table 5.2 summarizes the optimization strategies for this treatment regimen. In a
comprehensive review of seven studies, all but one [234] consistently utilized a current intensity of 2mA at the stimulation site. In the exception, which compared the
effects of tDCS and HD-tDCS, a lower intensity of 0.5mA was employed for
HD-tDCS.The authors posited that this reduced intensity could account for the lack
of signicant effects observed in their ndings.
Moreover, another study that varied both current intensity (1mA vs. 2mA) and
stimulation duration (10 min vs. 20 min) demonstrated that the combination of
2mA for 20min yielded signicantly greater efcacy [235].