Theta Burst Stimulation Research Articles

Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé.

Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects. The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests. D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression. An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD.

Time dependent changes in protein expression induced by intermittent theta burst stimulation in a cell line

BackgroundIntermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, is recognized for its ability to modulate cortical neuronal activity. However, its effects over time and the dynamics following stimulation are less well understood. Understanding the temporal dynamics of iTBS effects is essential for optimizing the timing and frequency of stimulation in therapeutic applications.ObjectiveThis study investigated the temporal changes in protein expression induced by iTBS in Neuro-2a cells.MethodsWe analyzed protein expression in retinoic acid-differentiated Neuro-2a cells at multiple time points — 0.5, 3, 6, 12, and 24 hours post-iTBS — using Western blot and immunocytochemistry techniques.ResultsOur findings reveal a significant early increase in neurotransmitter receptor subunits, neurotrophic factors, and cytoskeletal proteins within the first 0.5 hour following iTBS. Notably, proteins such as mGLuR1, NMDAR1, GABBR2, and β-tubulin III showed substantial increase in expression. However, the effects of iTBS on protein expression was not sustained at later timepoints.ConclusionOur results suggest that iTBS can transiently alter the expression of specific proteins in Neuro-2a cells. Future research should investigate the potential benefits of repeated stimulations within the early time window to refine iTBS interventions, potentially expanding their research and clinical applications.

Prolonged transcranial magnetic stimulation in a pregnant patient with treatment-resistant depression: a case report

IntroductionPerinatal depression is a serious and highly prevalent medical condition in the USA. Nearly 85% of individuals with perinatal depression go untreated, leading to significant morbidity and mortality. There is an urgent need to develop and advance safe and effective treatments for perinatal depression. Transcranial magnetic stimulation is an established intervention for depression in non-pregnant individuals yet is not well studied in perinatal depression.Case presentationA 33-year-old pregnant Latina female presented with severe, recurrent, treatment-resistant depression and suicidal ideation. The patient had previously trialed psychotherapy, multiple antidepressants, and mood stabilizers and had achieved remission with lithium prior to pregnancy. Due to pregnancy and fetal safety concerns, the patient discontinued lithium and consequently suffered progressive worsening of perinatal depression. At 24 weeks gestation and after additional failed medication trials, a prolonged course of transcranial magnetic stimulation was initiated. Following 46 transcranial magnetic stimulation treatments over 9 weeks using two protocol types (repetitive transcranial magnetic stimulation and intermittent theta burst stimulation), she achieved near-remission of perinatal depression and resolution of suicidal ideation. There were no identified maternal or fetal adverse events at 6 weeks post-delivery.ConclusionTo our knowledge, this is the first published case of a pregnant individual with perinatal depression who received and tolerated a prolonged transcranial magnetic stimulation course with two distinct protocols (repetitive transcranial magnetic stimulation and intermittent theta burst stimulation) with clinically significant response. Transcranial magnetic stimulation is a well-tolerated and effective intervention that warrants further investigation for use in treatment-resistant perinatal depression.

Effects of Continuous Theta Burst Stimulation on Contralateral Primary Motor Cortex: A Concurrent TMS-EEG Study.

Continuous theta burst stimulation (cTBS) is a non-invasive brain stimulation technique. cTBS modulation is an effective treatment for motor dysfunction rehabilitation in post-stroke patients. However, there's currently a lack of research on the effects of cTBS stimulation on the contralesional hemisphere. To better understand the role of cTBS in motor rehabilitation, we investigated the neuroregulatory mechanisms of cTBS in the contralateral cortex using transcranial magnetic stimulation-evoked electroencephalography (TMS-EEG). In this randomized, sham-controlled, single-blind study, 18 healthy subjects received two separate stimulation conditions:cTBS or sham stimulation applied to the left M1. TMS-EEG measurements were taken before and immediately after stimulation. We investigated the TMS-evoked potentials (TEPs), evoked oscillatory responses (EOR), and phase synchronization index(PSI) of TMS-EEG. The effects of cTBS were analyzed using two-way repeated measures analysis of variance (RMANOVA). There was a significant "cTBS condition×time" interaction effect on the theta and gamma bands of EOR, as well as on inter-hemisphere PSI (inter-PSI) and global PSI in both cTBS stimulation conditions. (theta:F=4.526,p=0.041;gamma:F=5.574,p=0.024;inter-PSI:F=5.028,p=0.032;global PSI:F=5.129,p=0.030).After real cTBS modulation, the energy in the theta and gamma frequency bands was significantly higher than before (theta: F=5.747, p=0.022; gamma: F=5.545, p=0.024). The inter-PSI and global PSI significantly increased after real cTBS modulation (inter-PSI: F=6.209, p=0.018; global PSI: F=6.530, p=0.015). cTBS modulation significantly increased EOR and PSI in contralateral brain regions, thereby enhancing cortical excitability and cortical functional connectivity throughout the brain. This provides a theoretical basis for cTBS neuromodulation in stroke patients.

Randomised controlled trial comparing different intersession intervals of intermittent theta burst delivered to the dorsal medial prefrontal cortex

BackgroundIntermittent theta burst stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS) that can be administered in a fraction of the time of standard rTMS. Applying multiple daily...

Extended course accelerated intermittent theta burst stimulation as a substitute for depressed patients needing electroconvulsive therapy.

In response to restrictions on electroconvulsive therapy (ECT) access during COVID-19, we designed a trial to assess the clinical outcomes service impacts, employing an extended course of accelerated intermittent theta burst stimulation (aiTBS), in patients with moderate to severe depression in need of ECT. This open label clinical trial was comprised of 3 phases: (i) an acute phase, where iTBS treatments were administered 8 times daily, for up to 10 days; (ii) a tapering phase of 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks; and (iii) a symptom-based relapse prevention phase, whereby treatments were scheduled based on symptom re-emergence, for up to 6 months. Of the 155 patients who completed the acute phase of the study, the remission rate was 16.1%. The mean reduction from baseline on the HRSD-24 was 29.4% (p < 0.001) and the response rate was 25.2%. Of the 110 patients who completed the tapering phase, the mean reduction from baseline was 42.6% (p < 0.001) and response and remission rates were 49.6% and 34.8%, respectively. Of the 61 patients who were eligible for the relapse prevention phase, 43 completed, with a mean reduction from baseline of 60.1% (p < 0.001); 7 patients relapsed during this phase. This study demonstrated that an extended aiTBS protocol safely led to meaningful clinical outcomes in patients with severe depression, who otherwise would have received ECT, and thus reduced pressure on ECT services during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04384965 ( https://clinicaltrials.gov/study/NCT04384965?term=NCT04384965&rank=1 ).

Theta-burst transcranial magnetic stimulation attenuates chronic ischemic demyelination and vascular cognitive impairment in mice

Vascular cognitive impairment and dementia (VCID) is mainly caused by chronic cerebral hypoperfusion and subsequent white matter lesions. Noninvasive transcranial magnetic stimulation has been utilized in treating various neurological disorders. However, the function of theta-burst transcranial magnetic stimulation on VCID remains to be defined. We utilized 4-week bilateral carotid artery stenosis model of male mice to mimic VCID. Intermittent theta-burst stimulation (iTBS) or consecutive theta-burst stimulation (cTBS) was administered for 14 consecutive days. Through luxol fast blue staining, electron microscopy and immunofluorescence, we found that iTBS, not cTBS, significantly improved demyelination, axonal damage and β-amyloid deposition, without affecting cerebral blood flow in VCID mice. At cellular levels, iTBS rescued the loss of mature oligodendrocytes, promoted precursor cell differentiation, and inhibited pro-inflammatory activation of astrocytes and microglia. Notably, iTBS attenuated cognitive deterioration in both short-term retention and long-term spatial memory of VCID mice as indicated by serial neurobehavioral tests. To explore the molecular involvement of iTBS, mRNA sequencing was carried out. By real-time PCR and combined RNA fluorescence in situ hybridization with immunofluorescence, iTBS was confirmed to increase Rxrg expression specifically in mature oligodendrocytes. Collectively, iTBS could ameliorate vascular cognitive dysfunction, probably via mitigating white matter lesions and neuroinflammation in the corpus callosum. Rxrg signaling in mature oligodendrocytes, which was increased by iTBS, might be a potential target for VCID treatment.

A causal role of the right dorsolateral prefrontal cortex in random exploration

Decision to explore new options with uncertain outcomes or exploit familiar options with known outcomes is a fundamental challenge that the brain faces in almost all real-life decisions. Previous studies have shown that humans use two main explorative strategies to negotiate this explore-exploit tradeoff. Exploring for the sake of information is called directed exploration, and exploration driven by behavioral variability is known as random exploration. While previous neuroimaging studies have shown different neural correlates for these explorative strategies, including right frontopolar cortex (FPC), right dorsolateral prefrontal cortex (DLPFC), and dorsal anterior cingulate cortex (dACC), there is still a lack of causal evidence for most of these brain regions. Here, we focused on the right DLPFC, which was previously supported to be involved in exploration. Using the continuous theta burst stimulation (cTBS) and Horizon task on twenty-five healthy right-handed adult participants, we showed that inhibiting rDLPFC did not change directed exploration but selectively reduced random exploration, by increasing reward sensitivity over the average reward of each option. This suggests a causal role for rDLPFC in random exploration, and further supports dissociable neural implementations for these two explorative strategies.

Metabotropic NMDAR Signaling Contributes to Sex Differences in Synaptic Plasticity and Episodic Memory.

NMDA receptor (NMDAR) - mediated calcium influx triggers the induction and initial expression of Long-Term Potentiation (LTP). Here we report that in male rodents ion flux-independent (metabotropic) NMDAR signaling is critical for a third step in the production of enduring LTP, i.e., cytoskeletal changes that stabilize the activity-induced synaptic modifications. Surprisingly, females rely upon estrogen receptor alpha (ERα) for the metabotropic NMDAR operations used by males. Blocking NMDAR channels with MK-801 eliminated LTP expression in hippocampal field CA1 of both sexes but left intact theta burst stimulation (TBS)-induced actin polymerization within dendritic spines. A selective antagonist (Ro25-6981) of the NMDAR GluN2B subunit had minimal effects on synaptic responses but blocked actin polymerization and LTP consolidation in males only. Conversely, an ERα antagonist thoroughly disrupted TBS-induced actin polymerization and LTP in females while having no evident effect in males. In an episodic memory paradigm, Ro25-6981 prevented acquisition of spatial locations by males but not females whereas an ERα antagonist blocked acquisition in females but not males. Sex differences in LTP consolidation were accompanied by pronounced differences in episodic memory in tasks involving a minimal (for learning) cue-sampling. Males did better on acquisition of spatial information whereas females had much higher scores than males on tests for acquisition of the identity of cues (episodic 'what') and the order in which the cues were sampled (episodic 'when'). We propose that sex differences in synaptic processes used to stabilize LTP result in differential encoding of the basic elements of episodic memory.Significance Statement Calcium influx through NMDARs has long been recognized as the initiating event for LTP. Results of the present studies call for a substantial revision to this fundamental observation about learning-related synaptic plasticity. Specifically, we show cytoskeletal mechanisms that consolidate field CA1 LTP and episodic memory are triggered not by NMDAR-mediated calcium but by ion flux-independent (metabotropic) signaling. Males used metabotropic functions of the NMDARs for this purpose whereas females relied upon synaptic estrogen receptors. This unprecedented instance of sex differences in synaptic function was accompanied by surprisingly large male/female differences in the acquisition of the three basic elements of episodic memory.

The DLPFC is centrally involved in resolving Stroop conflicts, suppressing distracting sensory input within the auditory and visual system

IntroductionCognitive control is a prerequisite for successful, goal-oriented behavior. The dorsolateral prefrontal cortex (DLPFC) is assumed to be a key player in applying cognitive control; however, the neural mechanisms by which this process is accomplished are still unclear.MethodsTo further address this question, an audiovisual Stroop task was used, comprising simultaneously presented pictures and spoken names of actors and politicians. Depending on the task block, participants had to indicate whether they saw the face or heard the name of a politician or an actor (visual vs. auditory blocks). In congruent trials, both stimuli (visual and auditory) belonged to the same response category (actor or politician); in incongruent trials, they belonged to different categories. During this task, activity in sensory target regions was measured via functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively. Specifically, fNIRS was used to monitor activity levels within the auditory cortex, while the EEG-based event-related potential of the N170 was considered as a marker of FFA (fusiform face area) involvement. Additionally, we assessed the effects of inhibitory theta-burst stimulation—a specific protocol based on repetitive transcranial magnetic stimulation (rTMS)—over the right DLPFC. Non-invasive brain stimulation is one of the few means to draw causal conclusions in human neuroscience. In this case, rTMS was used to temporarily inhibit the right DLPFC as a presumed key player in solving Stroop conflicts in one of two measurement sessions; then, effects were examined on behavioral measures as well as neurophysiological signals reflecting task-related activity in the frontal lobes and sensory cortices.ResultsThe results indicate a central role of the DLPFC in the implementation of cognitive control in terms of a suppression of distracting sensory input in both the auditory cortex and visual system (FFA) in high-conflict situations. Behavioral data confirm a reduced Stroop effect following previous incongruent trials (“Gratton effect”) that was only accomplished with an intact DLPFC (i.e., following placebo stimulation).DiscussionBecause non-invasive brain stimulation is uniquely suited to causally test neuroscientific hypotheses in humans, these data give important insights into some of the mechanisms by which the DLPFC establishes conflict resolution across different sensory modalities.

A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI

BackgroundEmerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce...

Cross-Task Differences in Frontocentral Cortical Activations for Dynamic Balance in Neurotypical Adults.

Although significant progress has been made in understanding the cortical correlates underlying balance control, these studies focused on a single task, limiting the ability to generalize the findings. Different balance tasks may elicit cortical activations in the same regions but show different levels of activation because of distinct underlying mechanisms. In this study, twenty young, neurotypical adults were instructed to maintain standing balance while the standing support surface was either translated or rotated. The differences in cortical activations in the frontocentral region between these two widely used tasks were examined using electroencephalography (EEG). Additionally, the study investigated whether transcranial magnetic stimulation could modulate these cortical activations during the platform translation task. Higher delta and lower alpha relative power were found over the frontocentral region during the platform translation task when compared to the platform rotation task, suggesting greater engagement of attentional and sensory integration resources for the former. Continuous theta burst stimulation over the supplementary motor area significantly reduced delta activity in the frontocentral region but did not alter alpha activity during the platform translation task. The results provide a direct comparison of neural activations between two commonly used balance tasks and are expected to lay a strong foundation for designing neurointerventions for balance improvements with effects generalizable across multiple balance scenarios.

Low-Frequency rTMS in the Management of Auditory Hallucination Nonresponsive to ECT, Clozapine, and Continuous Theta Burst Stimulation

Low-Frequency rTMS in the Management of Auditory Hallucination Nonresponsive to ECT, Clozapine, and Continuous Theta Burst Stimulation

Effect of intermittent theta burst stimulation on upper limb function in stroke patients: a systematic review and meta-analysis.

Stroke is a serious health issue that affects individuals, families, and society. Particularly, the upper limb dysfunction caused by stroke significantly reduces the quality of life for patients and may lead to psychological issues. Current treatment modalities are not fully effective in helping patients regain upper limb motor function to optimal levels. Therefore, there is an urgent need to explore new rehabilitation methods to address this issue. The purpose of this meta-analysis and systematic review is to explore the effects of intermittent theta burst stimulation (iTBS) on upper limb function in stroke patients. We searched PubMed, Cochrane Library, Embase, Web of Science, PEDro and China National Knowledge Internet as of April 8, 2024. Retrieved a total of 100 articles. Standardized mean differences (SMDs) and 95% confidence intervals (CI) were calculated. The study included a total of 9 trials and involved 224 patients. The results demonstrate that compared to the control group, iTBS therapy significantly improved Fugl-Meyer assessment-upper extremity (FMA-UE) scores (SMD = 0.88; 95% CI = 0.11-1.66; P = 0.03, I 2 = 84%), Action Research Arm Test (ARAT) scores (SMD = 0.83; 95% CI = 0.16-1.50; P = 0.02, I 2 = 57%), and Barthel Index (BI) scores (SMD = 0.93; 95% CI = 0.53-1.32; P < 0.0001, I 2 = 0%) in stroke patients. The comprehensive evidence suggests that iTBS has superior effects in improving upper limb function and activities of daily living in stroke patients.

Role of Accelerated Continuous Theta Burst Stimulation in Hand Dystonia: from Acute Phase to Maintenance Treatment

Role of Accelerated Continuous Theta Burst Stimulation in Hand Dystonia: from Acute Phase to Maintenance Treatment

Continuous Theta Burst Stimulation Inhibits Oxidative Stress-Induced Inflammation and Autophagy in Hippocampal Neurons by Activating Glutathione Synthesis Pathway, Improving Cognitive Impairment in Sleep-Deprived Mice.

Sleep deprivation (SD) has been reported to have a negative impact on cognitive function. Continuous theta burst stimulation (cTBS) shows certain effects in improving sleep and neurological diseases, and its molecular or cellular role in SD-induced cognition impairment still need further exploration. In this study, C57BL/6 mice were subjected to 48h of SD and cTBS treatment, and cTBS treatment significantly improved SD-triggered impairment of spatial learning and memory abilities in mice. Additionally, cTBS reduced malondialdehyde levels, increased superoxide dismutase activities, and inhibited the production of inflammatory cytokines, alleviating oxidative stress and inflammation levels in hippocampal tissues of SD model mice. cTBS decreased LC3II/LC3I ratio, Beclin1 protein levels, and LC3B puncta intensity, and elevated p62 protein levels to suppress excessive autophagy in hippocampal tissues of SD-stimulated mice. Then, we proved that inhibiting oxidative stress alleviated inflammation, autophagy, and death of hippocampal neuron cells through an in vitro cellular model for oxidative stress, and cTBS treatment promoted the production of glutathione (GSH), the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expression of GSH synthesis-related genes to enhance antioxidant capacity in hippocampal tissues of SD mice. An Nrf2 inhibitor ML385 or a GSH synthesis inhibitor BSO reversed the alleviating effects of cTBS treatment on oxidative stress-associated damage of hippocampal tissues and cognitive impairment in SD model mice. Altogether, our study demonstrated that cTBS mitigates oxidative stress-associated inflammation and autophagy through activating the Nrf2-mediated GSH synthesis pathway, improving cognitive impairment in SD mice.

Therapeutic Effects of Theta Burst Stimulation on Cognition Following Brain Injury

Therapeutic Effects of Theta Burst Stimulation on Cognition Following Brain Injury

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.

Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but thishas not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12months except for short-term (< 2weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.

Increasing mind wandering with accelerated intermittent theta burst stimulation over the left dorsolateral prefrontal cortex

Mind wandering (MW) is the intentional or unintentional experience of attending to internal task-unrelated thoughts while being occupied with an external task. Even though maintaining task focus is assumed to require executive functions (EF), it is not clear how and to what extent MW and EF interact. Research has found that activity in the dorsolateral prefrontal cortex (DLPFC) is associated with EF and MW. To understand the causal role of the DLPFC in relation to MW and EF, researchers have turned to non-invasive brain stimulation. Thus far, most studies have used transcranial direct current stimulation, but the results have been inconclusive. To further elucidate the relationship between the DLPFC, EF and MW, we conducted a pre-registered, sham-controlled, triple-blinded within-subject experiment by combining intermittent theta burst stimulation (iTBS) interleaved with a recently developed MW-EF task. In contrast to our expectations, participants reported significantly more MW following real iTBS as compared to sham stimulation. However, at the same time, psychomotor precision and EF improved, indicating that participants were able to engage in resource-intensive MW while simultaneously performing well on the task. We argue that iTBS enhanced the underlying executive resources that could be used to increase both MW and task performance in line with the resource-control view of MW. This finding opens exciting avenues for studying the complex interplay between MW and EF and provides empirical support for the utility of iTBS in improving executive performance during a demanding cognitive task.

Polysomnographically mediated cognitive improvements in individuals with insomnia symptoms following continuous theta-burst stimulation of the default mode network

IntroductionInsomnia is associated with mild cognitive impairment, although the mechanisms of this impairment are not well-understood. Timing of slow-wave and rapid eye movement sleep may help explain cognitive impairments common in insomnia. This investigation aimed to determine whether cognitive changes following continuous theta-burst stimulation (cTBS) are attributable to active stimulation, polysomnographic parameters of sleep, or both.MethodData presented here are part of a pilot clinical trial aiming to treat insomnia by targeting a node in the default mode network using an inhibitory 40-s (cTBS). A double-blind counterbalanced sham-controlled crossover design was conducted. Participants (N = 20) served as their own controls on two separate in-laboratory visits—one with active cTBS and the other with sham cTBS. Each visit included cognitive assessments before and after stimulation and following a night of sleep in the lab monitored with polysomnography.ResultsSlow wave sleep duration influenced working memory in the active cTBS condition, with shorter duration predicting improvements in working memory post sleep (B = −0.003, p = 0.095). Onset latency to rapid eye movement sleep predicted subsequent working memory, regardless of treatment condition (B = −0.001, p = 0.040). Results suggest that changes in attention and processing speed were primarily due to slow wave sleep onset (B = −0.001, p = 0.017) and marginally predicted by slow wave sleep duration (B = 0.002, p = 0.081) and sleep efficiency (B = 0.006, p = 0.090).ConclusionsFindings emphasize the important role that timing of slow-wave and rapid eye movement sleep have on information processing. Future work using larger sample sizes and more stimulation sessions is needed to determine optimal interactions between timing and duration of slow wave and rapid eye movement throughout the sleep period.Clinical trial registrationThis study is registered on ClinicalTrials.gov (NCT04953559). https://clinicaltrials.gov/study/NCT04953559?locStr=Arizona&amp;amp;country=United%20States&amp;amp;state=Arizona&amp;amp;cond=insomnia&amp;amp;intr=tms%20&amp;amp;rank=1