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•Despite their major effects on positive symptoms, antipsychotics do not have a significant effect on cognition in schizophrenia•Bilateral high frequency rTMS targeting dorsolateral prefrontal cortices has been effective on working memory•Bilateral 20 Hz rTMS improved attention and verbal working memory in schizophrenia patients,•It also improved t...
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... this study, 21 (11:10; active:sham) subjects with schizophrenia and 11 healthy control subjects were analyzed. Subject selection and randomization diagram is shown in the Fig. 1. A total of 41 subjects with schizophrenia were recorded. 17 of them did not matched all the criteria, so only 24 subjects have been included. A female subject with schizophrenia had to leave the study at 17th session of the treatment because of a holiday plan with her family, two ones from the sham group left the study at 3rd and 16th ...
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Objective: This study aimed to determine the minimal scanning duration of functional magnetic resonance imaging (fMRI) for producing individualized repetitive transcranial magnetic stimulation (rTMS) targets that are superior to the group-level targets.
Materials and Methods: This study included 30 healthy subjects and 20 depressive patients with h...
Citations
... Brunelin and colleagues correctly state that utilizing multiple search databases is also necessary in a systematic review (Bramer et al., 2017), which could theoretically identify more studies that fit the search criteria. In this instance, the 21 articles they identified are all indexed on the PubMed Regarding the studies not included in our review, we thank Brunelin and colleagues for bringing these 21 additional articles utilizing accelerated rTMS in schizophrenia to our attention (Basavaraju et al., 2020;Basavaraju et al., 2021;Bation et al., 2021;Bor et al., 2009;Brady et al., 2019;Demirtas-Tatlidede et al., 2010;Dlabac-de Lange et al., 2015;Dollfus et al., 2018;Dollfus et al., 2008;Güleken et al., 2020;Jardri et al., 2012;Kim et al., 2014;Kimura et al., 2016;Koops et al., 2016;Montagne-Larmurier et al., 2009;Poulet et al., 2005;Poulet et al., 2009;Poulet et al., 2008;Rachid et al., 2013;Tyagi et al., 2022). We further commend the authors for reporting the study parameters using the same table format as in our review, which provides the reader a nice complement to Supplementary Tables 1-2 in Caulfield et al., 2022. ...
... First, of the 21 papers, 8 did not include abstracts or keywords, which precluded them from being identified in our literature search (Basavaraju et al., 2020;Bor et al., 2009;Dollfus et al., 2008;Jardri et al., 2012;Poulet et al., 2009;Poulet et al., 2008;Rachid et al., 2013). Of the 13 papers that had abstracts, 8 neither used terminology nor described delivering multiple rTMS sessions per day in the title, abstract, or keywords (Demirtas-Tatlidede et al., 2010;Dlabac-de Lange et al., 2015;Dollfus et al., 2018;Güleken et al., 2020;Kim et al., 2014;Koops et al., 2016;Montagne-Larmurier et al., 2009;Poulet et al., 2005). The remaining 5 articles had abstracts describing a delivery schedule of multiple rTMS sessions within a day (Basavaraju et al., 2021;Bation et al., 2021;Brady et al., 2019;Kimura et al., 2016;Tyagi et al., 2022). ...
... TMS is approved for the treatment of major depression (https:// www.accessdata.fda.gov/cdrh_docs/pdf6/K061053.pdf) and since the negative symptoms of schizophrenia and the symptoms of major depression both represent deficits of normal functions, TMS has also been explored as a potential treatment of negative symptoms among patients with schizophrenia [15][16][17][18] . Since the most recent reviews of the literature on TMS for treatment of negative symptoms [15][16][17][18] , several trials have been conductedsome using novel stimulation parameters as well as neuronavigation to improve targeting [19][20][21][22][23][24][25][26][27] . Due to these developments in the field, an updated synthesis would be of relevance. ...
... The means and standard deviations of PANSS-N was the most common missing piece of information (i.e., from studies where only the total PANSS scores were reported). From these 35 studies, three author groups provided data 21,26,35 , and data were extracted from graphs in an additional eight studies 27,[36][37][38][39][40][41][42] . Hence, 24 articles were excluded due to nonavailable data . ...
... Hence, 24 articles were excluded due to nonavailable data . In total, the search yielded 45 includable studies, with 51 comparisons as a result of studies including multiple interventions [19][20][21][22][23][24][25][26][27][35][36][37][38][39][40][41][42] . No additional studies were found in citations or in the database of clinicaltrials.gov. ...
Several trials have shown preliminary evidence for the efficacy of transcranial magnetic stimulation (TMS) as a treatment for negative symptoms in schizophrenia. Here, we synthesize this literature in a systematic review and quantitative meta-analysis of double-blind randomized controlled trials of TMS in patients with schizophrenia. Specifically, MEDLINE, EMBASE, Web of Science, and PsycINFO were searched for sham-controlled, randomized trials of TMS among patients with schizophrenia. The effect of TMS vs. sham on negative symptoms in each study was quantified by the standardized mean difference (SMD, Cohen’s d) with 95% confidence intervals (95%CI) and pooled across studies using an inverse variance random effects model. We identified 57 studies with a total of 2633 participants that were included in the meta-analysis. The pooled analysis showed statistically significant superiority of TMS (SMD = 0.41, 95%CI: 0.26; 0.56, p-value < 0.001), corresponding to a number needed to treat of 5. Furthermore, stratified analyses suggested that TMS targeting the left dorsolateral prefrontal cortex and using a stimulation frequency >1 Hz was most efficacious. There was, however, substantial heterogeneity and high risk of bias among the included studies. In conclusion, TMS appears to be an efficacious treatment option for patients with schizophrenia suffering from negative symptoms, but the optimal TMS parameters are yet to be established.
... In the schizophrenic spectrum thirteen studies were included in total. Five randomized trials had statistically significant results targeting the DLPFC ( Barr et al., 2013;Guan et al., 2020;Güleken et al., 2020;Mogg et al., 2007). Notably, in a parallel-design shamcontrolled study which lasted eight weeks, including in total 110 patients, a significant improvement in short term memory was noticed only for the active treatment group of 20 Hz but not for the active treatment group of 10 Hz stimulation frequency (Xiu et al., 2020). ...
... Improvement of other cognitive symptoms 43 (Hoffman et al., 2013) HVLT Baseline, after 3rd session, after 8th session, after 13th session No improvement in verbal memory and working memory. A significant improvement in auditory hallucinations 52 (Güleken et al., 2020) DST backwards The day before the first session, the following day after the 20th session Improvement in working memory (p < 0.05). Improvement of other cognitive symptoms 60 (Cohen et al., 1999) two subtests of the Wechsler memory scale 24 hours before the beginning of the treatment, 24 hours after the last session A significant improvement only in delayed visual memory (p < 0.05). ...
... ( Barr et al., 2013Barr et al., , 2011Fitzgerald et al., 2005;Francis et al., 2019;Guan et al., 2020;Güleken et al., 2020;Guse et al., 2013;Hasan et al., 2016;Hoffman et al., 2013;Mittrach et al., 2010;Mogg et al., 2007;Schneider et al., 2008;Xiu et al., 2020;Zhuo et al., ( Koch et al., 2018;Padala et al., 2018;Rutherford et al., 2015;Turriziani et al., 2012) (Hill et al., 2020;Hulst et al., 2017) Randomized singleblind parallel design (Fitzgerald et al., 2020(Fitzgerald et al., , 2018(Fitzgerald et al., , 2009Hoy et al., 2012;Latif et al., 2020;Rosa et al., 2006;Wajdik et al., 2014;Yang et Open-label (Fabre et al., 2004;Furtado et al., 2013;Harel et al., 2014Harel et al., , 2011Isserles et al., 2011;Kedzior et al., 2012;Levkovitz et al., 2009;Martis et al., 2003;Pallanti et al., 2012;Schulze-Rauschenbach et al., 2005;Triggs et al., 1999) (Cohen et al., 1999;Demirtas-Tatlidede et al., 2010;Levkovitz et al., 2011;Oh and Kim, 2011) (Rosenberg et al., 2002) ( Avirame et al., 2016;Bentwich et al., 2011;Devi et al., 2014;Gandelman-Marton et al., 2017;Nguyen et al., 2017;Rabey and Dobronevsky, 2016;Rutherford et al., 2015;Velioglu et al., 2021;Wu et al., 2020) ...
Objective
Repetitive transcranial magnetic stimulation (rTMS) is being used as a non-invasive, non-pharmacological treatment with emerging clinical applications. The objective of this systematic review is to assess the possible rTMS effect on memory performance in patients suffering from central nervous system diseases.
Methods
PubMed, Google Scholar, Science Direct and Cochrane Library were searched through April 2021 for rTMS clinical trials in neuropsychiatric conditions, assessing pre-post treatment patients’ memory performance with neuropsychological measures.
Results
One hundred and four clinical studies were included for evaluation. Overall, a large number of reports were detected with a positive outcome of patients’ memory performance, concerning primarily the working memory, whereas there were also inconsistent results. In particular, considerable results were observed in patients with mild cognitive impairment and early stage Alzheimer’s disease.
Conclusions
Despite the variability of reports and the limited ability to generalize our findings, this review offers further evidence regarding the possible use of rTMS as a memory enhancement tool.
Significance
The study provides an updated and broad review in the field and highlights the need for more adequate studies, focusing on treatment procedure characteristics, follow-up and maintenance options of this approach.
Optimal working memory (WM), the mental ability to internally maintain and manipulate task-relevant information, requires coordinated activity of dorsal-lateral prefrontal cortical (DLPFC) neurons. More specifically, during delay periods of tasks with WM features, DLPFC microcircuits generate persistent, stimulus-specific higher-frequency (e.g., gamma) activity. This activity largely depends on recurrent connections between parvalbumin positive inhibitory interneurons and pyramidal neurons in more superficial DLPFC layers. Due to the size and organization of pyramidal neurons (especially apical dendrites), local field potentials generated by DLPFC microcircuits are strong enough to pass outside the skull and can be detected using electroencephalography (EEG). Since patients with schizophrenia (SCZ) exhibit both DLPFC and WM abnormalities, EEG markers of DLPFC microcircuit activity during WM may serve as effective biomarkers or treatment targets. In this review, we summarize converging evidence from primate and human studies for a critical role of DLPFC microcircuit activity during WM and in the pathophysiology of SCZ. We also present a meta-analysis of studies available in PubMed specifically comparing frontal gamma activity between participants with SCZ and healthy controls, to determine whether frontal gamma activity may be a valid biomarker or treatment target for patients with SCZ. We summarize the complex cognitive and neurophysiologic processes contributing to neural oscillations during tasks with WM features, and how such complexity has stalled the development of neurophysiologic biomarkers and treatment targets. Finally, we summarize promising results from early reports using neuromodulation to target DLPFC neural activity and improve cognitive function in participants with SCZ, including a study from our team demonstrating that gamma-EEG neurofeedback increases frontal gamma power and WM performance in participants with SCZ. From the evidence discussed in this review, we believe the emerging field of neuromodulation, which includes extrinsic (electrical or magnetic stimulation) and intrinsic (EEG neurofeedback) modalities, will, in the coming decade, provide promising treatment options targeting specific neurophysiologic properties of specific brain areas to improve cognitive and behavioral health for patients with SCZ.KeywordsCortical microcircuitDLPFCEEGGammaNeurofeedbackSchizophreniaWorking memory
It has been reported in the previous literatures that high-frequency (HF) neuronavigated
repetitive transcranial magnetic stimulation (rTMS) may improve neurocognitive functioning in patients
with schizophrenia. Nonetheless, the heterogeneity of the research findings with regards to the
effectiveness of HF-rTMS on the neurocognitive functioning in patients with schizophrenia greatly
hinders its clinical application. The current study was designed to determine the predictive role of
BDNF variants for neurocognitive improvements after rTMS administration in veterans with schizophrenia.
109 hospitalized veterans with schizophrenia were randomly allocated to active HF-rTMS
(n=63) or sham stimulation (n=46) over left DLPFC for 4 consecutive weeks. Neurocognitive functions
were assessed by using the Repeatable Battery for the Assessment of Neuropsychological Status
(RBANS) at baseline and at the end of week 4. BDNF polymorphism was genotyped by the
technicians. Compared with sham stimulation sessions, the immediate memory performance was
significantly increased in active sessions after neuronavigated HF-rTMS administration. In addition,
patients with the CC homozygotes demonstrated greater improvement of immediate memory after
rTMS treatment, while T allele carriers showed no significant improvement in immediate memory
domain relative to baseline performance of immediate memory. Our findings suggest that add-on
neuronavigated HF-rTMS is beneficial on immediate memory only in patients with CC homozygotes,
but not in T allele carriers. This pilot study provides further evidence for BDNF as a promise
biomarker in predicting the clinical response to rTMS stimulation.
