Supplementary Motor Area Research Articles

Divergent subregional information processing in mouse prefrontal cortex during working memory

Working memory (WM) is a critical cognitive function allowing recent information to be temporarily held in mind to inform future action. This process depends on coordination between prefrontal cortex (PFC) subregions and other connected brain areas. However, few studies have examined the degree of functional specialization between these subregions throughout WM using electrophysiological recordings in freely-moving mice. Here we record single-units in three neighboring mouse medial PFC (mPFC) subregions—supplementary motor area (MOs), dorsomedial PFC (dmPFC), and ventromedial (vmPFC)—during a freely-behaving non-match-to-position WM task. The MOs is most active around task phase transitions, when it transiently represents the starting sample location. Dorsomedial PFC contains a stable population code, including persistent sample-location-specific firing during the delay period. Ventromedial PFC responds most strongly to reward-related information during choices. Our results reveal subregionally segregated WM computation in mPFC and motivate more precise consideration of the dynamic neural activity required for WM.

Effects of repetitive transcranial magnetic stimulation at different targets on brain function in stroke patients: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) can improve post stroke motor function. However, there is little research on targets. The purpose of this study is to investigate the effects of rTMS therapy with different targets on post stroke motor function and neural plasticity. Fifty-four subjects were randomly divided into M1 (Primary motor area) group, SMA (supplementary motor area) group and Sham group, and were given 10 Hz on the affected M1 area, SMA area and sham stimulation rTMS. The primary outcomes included Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE), Fugl-Meyer Assessment Lower Extremity Scale (FMA-LE) and Berg balance scale (BBS). Secondary outcomes: amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were analyzed by functional magnetic resonance imaging (fMRI) to evaluate brain functional activation and functional connectivity changes. The 2-way repeated-measures ANOVA revealed a significant group × time interaction (F = 23.494, p < 0.001; F = 10.801, p < 0.001; F = 17.812, p < 0.001) in the FMA-UE, FMA-LE and BBS scores. Post hoc analysis indicated that 4 weeks of SMA rTMS resulted in an increase in FMA-UE, FMA-LE and BBS scores compared with Sham group (p = 0.006; p = 0.033; p = 0.012), SMA group was significantly increased in BBS compared with M1 group (p = 0.034). Moreover, there were significant effects of time in all 3 groups in the FMA-UE, FMA-LE and BBS scores (p < 0.001). In addition, the increase of ALFF in the supramarginal gyrus on the affected side was correlated with better FMA-UE recovery, the increase of ALFF in the middle temporal gyrus and the middle frontal gyrus on the affected side was positively correlated with the improvement of BBS, and the ALFF in the cerebellum on the healthy side was negatively correlated with the improvement of BBS. There was a positive correlation between FC (SMA - ipsilateral cerebellum) changes and BBS changes in SMA group. In conclusion, SMA-rTMS intervention has a better recovery effect on motor dysfunction after stroke than Sham-rTMS. SMA-rTMS led to similar improvement on motor function but significantly greater improvement on balance compared to M1-rTMS, and this may pave a new way for stroke rehabilitation. Registration number: ChiCTR2200060955, https://www.chictr.org.cn/.

Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

Neural Dynamics Associated with Biological Variation in Normal Human Brain Regions.

The processes involved in encoding and decoding signals in the human brain are a continually studied topic, as neuronal information flow involves complex nonlinear dynamics. This study examines awake human intracranial electroencephalography (iEEG) data from normal brain regions to explore how biological sex influences these dynamics. The iEEG data were analyzed using permutation entropy and statistical complexity in the time domain and power spectrum calculations in the frequency domain. The Bandt and Pompe method was used to assess time series causality by associating probability distributions based on ordinal patterns with the signals. Due to the invasive nature of data acquisition, the study encountered limitations such as small sample sizes and potential sources of error. Nevertheless, the high spatial resolution of iEEG allows detailed analysis and comparison of specific brain regions. The results reveal differences between sexes in brain regions, observed through power spectrum, entropy, and complexity analyses. Significant differences were found in the left supramarginal gyrus, posterior cingulate, supplementary motor cortex, middle temporal gyrus, and right superior temporal gyrus. This study emphasizes the importance of considering sex as a biological variable in brain dynamics research, which is essential for improving the diagnosis and treatment of neurological and psychiatric disorders.

Brain activation in older adults with hypertension and normotension during standing balance task: an fNIRS study.

Hypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies. In this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate. The mean velocity of the COP in the medial-lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p < 0.001). The standing balance function of older adults with HT does not appear to be worse based on COP parameters than those of older adults with NT. This study revealed that the changes in the central cortex related to standing balance appear to be more indicative of balance control deficits in older adults with HT than changes in peripheral COP parameters, suggesting the importance of the early evaluation of cortical activation in older adults with HT at risk of falls.

Abnormal brain regional activity in acute thyrotoxic myopathy assessed by resting-state functional MRI.

The neurophysiological mechanisms underlying manifestations of bulbar paralysis in acute thyrotoxic myopathy (ATM) and the afflicted brain areas are unclear. We used resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional brain activities in patients with ATM. In total, 16 patients with ATM, 16 patients with hyperthyroidism without ATM, and 16 healthy controls underwent functional MRI scans. By calculating the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), we assessed variations in resting-state cerebral activity. The correlation between the resting-state functional indexes and clinical assessments was also explored. Compared to the hyperthyroid patients, patients with ATM had stronger ReHo in the left precentral gyrus, reduced ReHo in the left orbitofrontal gyrus (OFG), and decreased FC in the left precentral gyri, left superior frontal gyrus (SFG), and left middle frontal gyrus (MFG). Patients with ATM showed reduced fALFF and ReHo in the right SFG and decreased ReHo in the bilateral supplementary motor area (SMA). A significantly decreased FC in the left SFG and left MFG, right precentral gyrus, and the orbital part of the right interior frontal gyrus was observed in patients with ATM compared to healthy controls. Additionally, fALFF and ReHo values were positively correlated with serum thyroid-related hormones and antibodies. The findings of rs-fMRI demonstrate that particular brain regions' functional activity was aberrant in individuals with ATM, especially in SFG area. This finding may help with better understanding of underlying pathophysiology of patients with ATM.

Structural neuroanatomy of human facial behaviors.

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior were related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e. greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e. greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.

Safety and efficacy of targeting the supplementary motor area with double-cone deep transcranial magnetic stimulation vs figure-eight coil in treatment of obsessive-compulsive disorder with comorbid major depressive disorder

Background and objectiveThe Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone “deep” TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). MethodsSixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. ResultsSubjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. ConclusionsSMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation.

Structural and functional brain alterations in laryngeal dystonia: A coordinate-based activation likelihood estimation meta-analysis.

Laryngeal dystonia (LD) is an isolated, task-specific, focal dystonia characterized by intermittent spasms of laryngeal muscles impairing speech production. Although recent studies have demonstrated neural alterations in LD, the consistency of findings across studies is not well-established, limiting their translational applicability. We conducted a systematic literature search to identify studies reporting stereotactic coordinates of peak structural and functional abnormalities in LD patients compared to healthy controls, followed by a coordinate-based activation likelihood estimation meta-analysis. A total of 21 functional and structural neuroimaging studies, including 31 experiments in 521 LD patients and 448 healthy controls, met the study inclusion criteria. The multimodal meta-analysis of these studies identified abnormalities in the bilateral primary motor cortices, the left inferior parietal lobule and striatum, the right insula, and the supplementary motor area in LD patients compared to healthy controls. The meta-analytical findings reinforce the current view of dystonia as a neural network disorder and consolidate evidence for future investigations probing these targets with new therapies.

“Apathetic look” is a valuable indicator of intraoperative supplementary motor area syndrome during awake craniotomy

“Apathetic look” is a valuable indicator of intraoperative supplementary motor area syndrome during awake craniotomy

Delayed Recovery of Bilateral Supplementary Motor Area Syndrome After the Resection of a Central Neurocytoma

Delayed Recovery of Bilateral Supplementary Motor Area Syndrome After the Resection of a Central Neurocytoma

Alterations of perfusion and functional connectivity of the cingulate motor area are associated with psychomotor retardation in major depressive disorder

AbstractPsychomotor retardation, characterized by slowing of speech, thoughts, and a decrease of movements, is frequent in patients with major depressive disorder (MDD). However, its neurobiological correlates are still poorly understood. This study aimed to explore if cerebral blood flow (CBF) and resting state functional connectivity (rs-FC) of the motor network are altered in patients with MDD and if these changes are associated with psychomotor retardation. Thirty-six right-handed patients with depression and 19 right-handed healthy controls (HC) that did not differ regarding age and sex underwent arterial spin labelling (ASL) and resting-state functional MRI (rs-fMRI) scans. Psychomotor retardation was assessed with the motoric items of the core assessment of psychomotor change (CORE) questionnaire. Patients with MDD had more pronounced psychomotor retardation scores than HC. Patients with MDD had reduced CBF in bilateral cingulate motor area (CMA) and increased resting-state functional connectivity (rs-FC) between the cluster in the CMA and a cluster localized in bilateral supplementary motor areas (SMA). Furthermore, increased rs-FC between the CMA and the left SMA was associated with more pronounced psychomotor retardation. Our results suggest that reduced perfusion of the CMA and increased rs-FC between the CMA and the SMA are associated with psychomotor retardation in patients with depression.

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations: a functional magnetic resonance imaging study.

To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.

A comparative study of simulated electric fields of transcranial magnetic stimulation targeting different cortical motor regions.

This computational simulation study investigates the strength of transcranial magnetic stimulation (TMS)-induced electric fields (EF) in primary motor cortex (M1) and secondary motor areas. Our results reveal high interindividual variability in the strength of TMS-induced EF responses in secondary motor areas, relative to the stimulation threshold in M1. Notably, the activation of the supplementary motor area requires high-intensity stimulation, which could be attributed to the greater scalp-to-cortex distance observed over this area. These findings emphasize the importance of individualized planning using computational simulation for optimizing neuromodulation strategies targeting the cortical motor system.

Neuromechanisms of simulation-based arthroscopic skills assessment: a fNIRS study.

The neural mechanisms underlying differences in the performance of simulated arthroscopic skills across various skill levels remain unclear. Our primary objective is to investigate the learning mechanisms of simulated arthroscopic skills using functional near-infrared spectroscopy (fNIRS). We recruited 27 participants, divided into three groups: novices (n = 9), intermediates (n = 9), and experts (n = 9). Participants completed seven arthroscopic tasks on a simulator, including diagnostic navigation, triangulation, grasping stars, diagnostic exploration, meniscectomy, synovial membrane cleaning, and loose body removal. All tasks were videotaped and assessed via the simulator system and the Arthroscopic Surgical Skill Evaluation Tool (ASSET), while cortical activation data were collected using fNIRS. Simulator scores and ASSET scores were analyzed to identify different level of performance of all participants. Brain region activation and functional connectivity (FC) of different types of participants were analyzed from fNIRS data. Both the expert and intermediate groups scored significantly higher than the novice group (p < 0.001). There were significant differences in ASSET scores between experts and intermediates, experts and novices, and intermediates and novices (p = 0.0047, p < 0.0001, p < 0.0001), with the trend being experts > intermediates > novices. The intermediate group exhibited significantly greater activation in the left primary motor cortex (LPMC) and left prefrontal cortex (LPFC) compared to the novice group (p = 0.0152, p = 0.0021). Compared to experts, the intermediate group demonstrated significantly increased FC between the presupplementary motor area (preSMA) and the right prefrontal cortex (RPFC; p < 0.001). Additionally, the intermediate group showed significantly increased FC between the preSMA and LPFC, RPFC and LPFC, and LPMC and LPFC compared to novices (p = 0.0077, p = 0.0285, p = 0.0446). Cortical activation and functional connectivity reveal varying levels of activation intensity in the PFC, PMC, and preSMA among novices, intermediates, and experts. The intermediate group exhibited the highest activation intensity.

The Relevance of Dual Language Experience in Interhemispheric Brain Connectivity in Older Adults

Abstract Objectives to analyze the volumes of sections of the corpus callosum (CC) and the integrity of the interhemispheric fibers that connect homotopic regions of the frontal and temporal lobes in bilinguals and monolinguals and to correlate neuroimaging data with cognitive measures and bilingual variables. Method 107 bilinguals and 89 monolinguals from the 1Florida ADRC were clinically diagnosed as cognitively normal (CN), MCI, or dementia; mean age = 71.28 (10.94). CC volume was calculated from a T1-weighted scan using Freesurfer. Free water (FW) and free water-corrected fractional anisotropy (FAt) maps were calculated from a diffusion MRI scan within frontal and temporal transcallosal tracts (TCATT). Results Bilinguals had a larger proportion of the anterior CC volume compared to monolinguals independent of the diagnostic group. FAt values in the Supplementary Motor Area (SMA) and the inferior temporal lobe tracts (IT TCATTs) were higher in bilinguals compared to monolinguals indicating better white matter integrity. A significant interaction demonstrated that these values were higher in bilinguals for the dementia group. Correlations were significant between the SMA FW values and several cognitive tests particularly executive function tests in both language groups. In bilinguals, the IT TCATTs correlated with language test scores. FAt in the SMA TCATT correlated with the percentage of English exposure and FAt in the IT TCATTs positively correlated with English proficiency. Conclusions Bilingualism interacts with cognitive status in aging and is associated with CC volume and the integrity of white matter in the frontal and temporal lobes supporting its role in the increase of neural reserve.

Not All Stroop-Type Tasks Are Alike: Assessing the Impact of Stimulus Material, Task Design, and Cognitive Demand via Meta-analyses Across Neuroimaging Studies.

The Stroop effect is one of the most often studied examples of cognitive conflict processing. Over time, many variants of the classic Stroop task were used, including versions with different stimulus material, control conditions, presentation design, and combinations with additional cognitive demands. The neural and behavioral impact of this experimental variety, however, has never been systematically assessed. We used activation likelihood meta-analysis to summarize neuroimaging findings with Stroop-type tasks and to investigate whether involvement of the multiple-demand network (anterior insula, lateral frontal cortex, intraparietal sulcus, superior/inferior parietal lobules, midcingulate cortex, and pre-supplementary motor area) can be attributed to resolving some higher-order conflict that all of the tasks have in common, or if aspects that vary between task versions lead to specialization within this network. Across 133 neuroimaging experiments, incongruence processing in the color-word Stroop variant consistently recruited regions of the multiple-demand network, with modulation of spatial convergence by task variants. In addition, the neural patterns related to solving Stroop-like interference differed between versions of the task that use different stimulus material, with the only overlap between color-word, emotional picture-word, and other types of stimulus material in the posterior medial frontal cortex and right anterior insula. Follow-up analyses on behavior reported in these studies (in total 164 effect sizes) revealed only little impact of task variations on the mean effect size of reaction time. These results suggest qualitative processing differences among the family of Stroop variants, despite similar task difficulty levels, and should carefully be considered when planning or interpreting Stroop-type neuroimaging experiments.

Reducing pain by improving brain and muscle activity with motor cortical neuromodulation in women with interstitial cystitis/bladder pain syndrome: a study protocol for a randomized controlled trial

IntroductionInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction.This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes.Ethics and disseminationAll aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20–01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences.Trial registrationClinicalTrials.gov NCT04734847. Registered on February 1, 2021.

The Hippocampus Represents Information about Movements in Their Temporal Position in a Learned Motor Sequence.

Our repertoire of motor skills is filled with sequential movements that need to be performed in a specific order. Here, we used functional magnetic resonance imaging to investigate whether the human hippocampus, a region known to support temporal order in non-motor memory, represents information about the order of sequential motor actions in human participants (both sexes). We also examined such representations in other regions of the motor network (i.e., the premotor cortex, supplementary motor area, anterior superior parietal lobule, and striatum) already known for their critical role in motor sequence learning. Results showed that the hippocampus represents information about movements in their learned temporal position in the sequence, but not about movements or temporal positions in random movement patterns. Other regions of the motor network coded for movements in their learned temporal position, as well as movements and positions in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in primary, supplementary, and premotor cortices but not in striatal and parietal regions. Our findings deepen our understanding of how striatal and cortical regions contribute to motor sequence learning and point to the capacity of the hippocampus to represent movements in their temporal context, an ability possibly explaining its contribution to motor learning.

Metaanalysis of Repetitive Transcranial Magnetic Stimulation (rTMS) Efficacy for OCD Treatment: The Impact of Stimulation Parameters, Symptom Subtype and rTMS-Induced Electrical Field.

Background: Repetitive transcranial magnetic stimulation (rTMS) has recently demonstrated significant potential in treating obsessive-compulsive disorder (OCD). However, its effectiveness depends on various parameters, including stimulation parameters, OCD subtypes and electrical fields (EFs) induced by rTMS in targeted brain regions that are less studied. Methods: Using the PRISMA approach, we examined 27 randomized control trials (RCTs) conducted from 1985 to 2024 using rTMS for the treatment of OCD and conducted several meta-analyses to investigate the role of rTMS parameters, including the EFs induced by each rTMS protocol, and OCD subtypes on treatment efficacy. Results: A significant, medium effect size was found, favoring active rTMS (gPPC = 0.59, p < 0.0001), which was larger for the obsession subscale. Both supplementary motor area (SMA) rTMS (gPPC = 0.82, p = 0.048) and bilateral dorsolateral prefrontal cortex (DLPFC) rTMS (gPPC = 1.14, p = 0.04) demonstrated large effect sizes, while the right DLPFC showed a significant moderate effect size for reducing OCD severity (gPPC = 0.63, p = 0.012). These protocols induced the largest EFs in dorsal cognitive, ventral cognitive and sensorimotor circuits. rTMS protocols targeting DLPFC produced the strongest electrical fields in cognitive circuits, while pre-supplementary motor area (pre-SMA) and orbitofrontal cortex (OFC) rTMS protocols induced larger fields in regions linked to emotional and affective processing in addition to cognitive circuits. The pre-SMA rTMS modulated more circuits involved in OCD pathophysiology-sensorimotor, cognitive, affective, and frontolimbic-with larger electrical fields than the other protocols. Conclusions: While rTMS shows moderate overall clinical efficacy, protocols targeting ventral and dorsal cognitive and sensorimotor circuits demonstrate the highest potential. The pre-SMA rTMS appears to induce electrical fields in more circuits relevant to OCD pathophysiology.