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Background: Traumatic brain injury (TBI) and spinal cord injury (SCI) are acquired injuries to the central nervous system (CNS) caused by external forces that cause temporary or permanent sensory and motor impairments and the potential for long‐term disability or even death. These conditions currently lack effective treatments and impose substantial physical, social, and economic burdens on millions of people and families worldwide. TBI and SCI involve intricate pathological mechanisms, and the inflammatory response contributes significantly to secondary injury in TBI and SCI. It plays a crucial role in prolonging the post‐CNS trauma period and becomes a focal point for a potential therapeutic intervention. Previous research on the inflammatory response has traditionally concentrated on glial cells, such as astrocytes and microglia. However, increasing evidence highlights the crucial involvement of lymphocytes in the inflammatory response to CNS injury, particularly CD8+ T cells and NK cells, along with their downstream XCL1‐XCR1 axis. Objective: This review aims to provide an overview of the role of the XCL1‐XCR1 axis and the T‐cell response in inflammation caused by TBI and SCI and identify potential targets for therapy. Methods: We conducted a comprehensive search of PubMed and Web of Science using relevant keywords related to the XCL1‐XCR1 axis, T‐cell response, TBI, and SCI. Results: This study examines the upstream and downstream pathways involved in inflammation caused by TBI and SCI, including interleukin‐15 (IL‐15), interleukin‐12 (IL‐12), CD8+ T cells, CD4+ T cells, NK cells, XCL1, XCR1+ dendritic cells, interferon‐gamma (IFN‐γ), helper T0 cells (Th0 cells), helper T1 cells (Th1 cells), and helper T17 cells (Th17 cells). We describe their proinflammatory effect in TBI and SCI. Conclusions: The findings suggest that the XCL1‐XCR1 axis and the T‐cell response have great potential for preclinical investigations and treatments for TBI and SCI. [ABSTRACT FROM AUTHOR]

Objective: The primary aim of this study was to evaluate the influence of targeted interventions, administered through comprehensive geriatric assessments on the incidence of hospitalization‐related complications among older adults diagnosed with pulmonary diseases. Methods: A retrospective analysis of medical records encompassed individuals aged 75 years and older who were admitted to a lung center during the period spanning from March to June 2023. These admissions occurred in a context where standardized geriatric management protocols were systematically implemented. This study's scope extended to assessing the prevalence of hospital‐related complications, encompassing delirium and pressure ulcers. A rigorous multivariate logistic regression analysis was conducted to discern and characterize associated factors. Results: The integration of comprehensive geriatric assessment yielded a substantial reduction in in‐hospital complications among the cohort of 118 patients (mean age : 82.1 ± 5.6 years, 44.5% women). The incidence of delirium decreased from 53.3% to 21.8% [odds ratio (OR): 0.246, 95% confidence interval (CI): 0.134–0.450, p < 0.001], whereas the presence of pressure ulcers decreased from 43.9% to 25% (OR: 0.395, 95% CI: 0.217–0.715, p < 0.001). The multivariate analysis uncovered independent associations between delirium and variables including community‐acquired pneumonia (OR: 4.417, 95% CI : 1.574–12.395, p = 0.005), severe disability (OR: 2.981, 95% CI: 1.140–7.798, p = 0.026), and hearing loss (OR: 3.219, 95% CI : 1.260–8.170, p = 0.014). Prolonged hospital stays emerged as the sole factor significantly associated with pressure ulcers (OR: 1.071, 95% CI: 1.033–1.109). Furthermore, an intricate bidirectional relationship was evident between delirium and pressure ulcers (OR: 7.158, 95% CI: 2.962–17.300, p < 0.01). Conclusion: In conjunction with its consequent interventions, geriatric evaluation assumes a pivotal role in ameliorating adverse outcomes stemming from hospitalization among older adults afflicted with pulmonary ailments. This role gains particular salience among subpopulations characterized by heightened susceptibility, such as individuals coping with hearing loss and severe disability. [ABSTRACT FROM AUTHOR]

Astrocytes are the most abundant and widespread glial cells in the central nervous system. The heterogeneity of astrocytes plays an essential role in spinal cord injury (SCI) repair. Decellularised spinal cord matrix (DSCM) is advantageous for repairing SCI, but little is known regarding the exact mechanisms and niche alterations. Here, we investigated the DSCM regulatory mechanism of glial niche in the neuro‐glial‐vascular unit using single‐cell RNA sequencing. Our single cell sequencing, molecular and biochemical experiments validated that DSCM facilitated the differentiation of neural progenitor cells through increasing the number of immature astrocytes. Upregulation of mesenchyme‐related genes, which maintained astrocyte immaturity, causing insensitivity to inflammatory stimuli. Subsequently, we identified serglycin (SRGN) as a functional component of DSCM, which involves inducing CD44–AKT signalling to trigger human spinal cord‐derived primary astrocytes (hspASCs) proliferation and upregulation of genes related to epithelial–mesenchymal transition, thus impeding astrocyte maturation. Finally, we verified that SRGN‐COLI and DSCM had similar functions in the human primary cell co‐culture system to mimic the glia niche. In conclusion, our work revealed that DSCM reverted astrocyte maturation and altered the glia niche into the repairing phase through the SRGN‐mediated signalling pathway. [ABSTRACT FROM AUTHOR]

Background: Delirium, an acute and fluctuating decline in cognitive functioning, increases mortality and length of hospital stays (LOS) and adversely affects functional outcomes. Previous studies suggested that the incidence of delirium may be increased in right‐hemisphere strokes. Similarly, spatial neglect, a disabling deficit in unilateral spatial processing, is more common and more severe following a right‐sided stroke. Spatial neglect has been established as a risk factor for delirium. Objective: It was hypothesized that functionally relevant spatial neglect and delirium are associated in patients with right‐hemisphere stroke during acute inpatient rehabilitation. Data were examined from consecutive unilateral stroke patients evaluated with the 3‐minute diagnostic interview for confusion assessment method (3D‐CAM) and the Catherine Bergego Scale (CBS) via the Kessler Foundation Neglect Assessment Process (KF‐NAP). Design: A retrospective, cohort study. Setting: Data collected in an acute inpatient rehabilitation facility. Participants: Six hundred twenty six patients with stroke were included. Main Outcome Measures: The measures were the relative risk of patients with right‐hemisphere stroke having delirium when also positive for spatial neglect compared to patients with right‐hemisphere stroke without spatial neglect, the incidence of 3D‐CAM positive results by stroke hemisphere, and the effect of spatial neglect and delirium on functional outcomes for patients with right‐brain stroke patients. Results: There was a significantly higher risk of delirium in patients with right‐hemisphere stroke with spatial neglect compared to patients with right‐hemisphere stroke without spatial neglect. The rates of 3D‐CAM positive results were not statistically different for left‐ compared to right‐hemisphere strokes. Both delirium and spatial neglect had significant adverse effects on right‐hemisphere stroke patients' functional independence. Conclusions: The results demonstrate an association between spatial neglect and delirium in patients with right hemisphere stroke in the acute inpatient rehabilitation setting. Because of the negative effect of these impairments on functional outcomes after stroke, prevention, early detection, and targeted treatments should be prioritized for these patients. [ABSTRACT FROM AUTHOR]

Background: A growing body of research shows that drug monomers from traditional Chinese herbal medicines have antineuroinflammatory and neuroprotective effects that can significantly improve the recovery of motor function after spinal cord injury (SCI). Here, we explore the role and molecular mechanisms of Alpinetin on activating microglia-mediated neuroinflammation and neuronal apoptosis after SCI. Methods: Stimulation of microglia with lipopolysaccharide (LPS) to simulate neuroinflammation models in vitro, the effect of Alpinetin on the release of pro-inflammatory mediators in LPS-induced microglia and its mechanism were detected. In addition, a co-culture system of microglia and neuronal cells was constructed to assess the effect of Alpinetin on activating microglia-mediated neuronal apoptosis. Finally, rat spinal cord injury models were used to study the effects on inflammation, neuronal apoptosis, axonal regeneration, and motor function recovery in Alpinetin. Results: Alpinetin inhibits microglia-mediated neuroinflammation and activity of the JAK2/STAT3 pathway. Alpinetin can also reverse activated microglia-mediated reactive oxygen species (ROS) production and decrease of mitochondrial membrane potential (MMP) in PC12 neuronal cells. In addition, in vivo Alpinetin significantly inhibits the inflammatory response and neuronal apoptosis, improves axonal regeneration, and recovery of motor function. Conclusion: Alpinetin can be used to treat neurodegenerative diseases and is a novel drug candidate for the treatment of microglia-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

The course of delirium is associated with increased hospital costs, healthcare complications, increased mortality, and long‐term poor outcomes. Despite delirium being long recognised as one of the most important prognostic components of patients with illnesses, delirium remains poorly understood, effective management options are limited, and no effective treatment has yet been established. This review evaluated the effects of delirium on mortality, institutionalisation, and dementia in various situations to clarify its prognostic seriousness to elucidate important areas for clinical practice and future research. The effect of delirium on mortality in COVID‐19 patients was similar to that in other diseases. The effect of delirium on mortality in patients with delirium between the ages of 18 and 65 may be higher than in those with delirium aged over 65, but studies are scarce. Promoting recognition of delirium at all ages is needed. With careful attention to the specific factors in younger patients that contribute to delirium, healthcare providers may be able to decrease the poor impact of delirium on clinical outcomes. Evaluation of the association between interventions for delirium such as sedation in present clinical practice and the prognosis of delirium is lacking, and further clinical studies are essential. [ABSTRACT FROM AUTHOR]

Aims: To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients. Method: This was a retrospective study of perioperative medical data from patients undergoing non‐cardiac and non‐neurology surgery over 65 years old from January 2014 to August 2019. Forty‐six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC‐ROC), sensitivity, specificity, and precision. Results: In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765–0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%. Conclusions: The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model. [ABSTRACT FROM AUTHOR]

Background and Purpose: The timing of decision‐making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC‐MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high‐risk patients. This study aims to determine the comparability of axial and sagittal PC‐MRI measurements of spinal cord motion with the prospect of improving the clinical workup. Methods: Sixty‐four DCM patients underwent a PC‐MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland‐Altman analyses. Results: The comparability of axial and sagittal PC‐MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude:.810‐.940; p <.001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: −0.12 ± 0.30 cm/second). Bland‐Altman analysis showed a good agreement between axial and sagittal PC‐MRI scans (coefficients of repeatability: minimum −0.23 cm/second at C2; maximum −0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. Conclusions: This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC‐MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high‐risk patients and improve clinical decision‐making (ie, timing of decompression). [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to investigate pharmacodynamic effects of drugs targeting cortical excitability using transcranial magnetic stimulation (TMS) combined with electromyography (EMG) and electroencephalography (EEG) in healthy subjects, to further develop TMS outcomes as biomarkers for proof‐of‐mechanism in early‐phase clinical drug development. Antiepileptic drugs presumably modulate cortical excitability. Therefore, we studied effects of levetiracetam, valproic acid and lorazepam on cortical excitability in a double‐blind, placebo‐controlled, 4‐way cross‐over study. Methods: In 16 healthy male subjects, single‐ and paired‐pulse TMS‐EMG–EEG measurements were performed predose and 1.5, 7 and 24 hours postdose. Treatment effects on motor‐evoked potential, short and long intracortical inhibition and TMS‐evoked potential amplitudes, were analysed using a mixed model ANCOVA and cluster‐based permutation analysis. Results: We show that motor‐evoked potential amplitudes decreased after administration of levetiracetam (estimated difference [ED] −378.4 μV; 95%CI: −644.3, −112.5 μV; P <.01), valproic acid (ED −268.8 μV; 95%CI: −532.9, −4.6 μV; P =.047) and lorazepam (ED −330.7 μV; 95%CI: −595.6, −65.8 μV; P =.02) when compared with placebo. Long intracortical inhibition was enhanced by levetiracetam (ED −60.3%; 95%CI: −87.1%, −33.5%; P <.001) and lorazepam (ED −68.2%; 95%CI: −94.7%, −41.7%; P <.001) at a 50‐ms interstimulus interval. Levetiracetam increased TMS‐evoked potential component N45 (P =.004) in a central cluster and decreased N100 (P <.001) in a contralateral cluster. Conclusion: This study shows that levetiracetam, valproic acid and lorazepam decrease cortical excitability, which can be detected using TMS‐EMG–EEG in healthy subjects. These findings provide support for the use of TMS excitability measures as biomarkers to demonstrate pharmacodynamic effects of drugs that influence cortical excitability. [ABSTRACT FROM AUTHOR]

Key points: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits.Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG); however, it is unclear whether these two measures represent the same activity when assessing motor cortex.We found that TMS‐EMG and TMS‐EEG measures of motor cortex excitability are differentially affected by sensory confounds at different time points, masking any actual relationship between them in the time domain.In the frequency domain, local high‐frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform.Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population. Transcranial magnetic stimulation (TMS) is a powerful tool for investigating cortical circuits. Changes in cortical excitability following TMS are typically assessed by measuring changes in either conditioned motor‐evoked potentials (MEPs) following paired‐pulse TMS over motor cortex or evoked potentials measured with electroencephalography following single‐pulse TMS (TEPs). However, it is unclear whether these two measures of cortical excitability index the same cortical response. Twenty‐four healthy participants received local and interhemispheric paired‐pulse TMS over motor cortex with eight inter‐pulse intervals, sub‐ and suprathreshold conditioning intensities, and two different pulse waveforms, while MEPs were recorded from a hand muscle. TEPs were also recorded in response to single‐pulse TMS using the conditioning pulse alone. The relationships between TEPs and conditioned‐MEPs were evaluated using metrics sensitive to both their magnitude at each time point and their overall shape across time. The impacts of undesired sensory potentials resulting from TMS pulse and muscle contractions were also assessed on both measures. Both conditioned‐MEPs and TEPs were sensitive to re‐afferent somatosensory activity following motor‐evoked responses, but over different post‐stimulus time points. Moreover, the amplitude of low‐frequency oscillations in TEPs was strongly correlated with the sensory potentials, whereas early and local high‐frequency responses showed minimal relationships. Accordingly, conditioned‐MEPs did not correlate with TEPs in the time domain but showed high shape similarity with the amplitude of high‐frequency oscillations in TEPs. Therefore, despite the effects of sensory confounds, the TEP and MEP measures share a response component, suggesting that they index a similar cortical response and perhaps the same neuronal populations. Key points: TMS is commonly used to study excitatory/inhibitory neurotransmission in cortical circuits.Changes in cortical excitability following TMS are typically measured from hand (using EMG; limited to motor cortex) or scalp (using EEG); however, it is unclear whether these two measures represent the same activity when assessing motor cortex.We found that TMS‐EMG and TMS‐EEG measures of motor cortex excitability are differentially affected by sensory confounds at different time points, masking any actual relationship between them in the time domain.In the frequency domain, local high‐frequency oscillations in EEG recordings were minimally confounded by sensory artefacts and demonstrated strong correlations with EMG measures of cortical excitability across time, regardless of TMS intensity or waveform.Therefore, despite the effects of sensory artefacts, the two measures of motor cortex excitability share a response component, suggesting that they index a similar cortical activity and perhaps the same neuronal population. [ABSTRACT FROM AUTHOR]

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can depolarize the neurons directly under the coil when applied to the cerebral cortex, and modulate the neural circuit associated with the stimulation site, which makes it possible to measure the neurophysiological index to evaluate excitability and inhibitory functions. Concurrent TMS and electroencephalography (TMS‐EEG) has been developed to assess the neurophysiological characteristics of cortical regions other than the motor cortical region noninvasively. The aim of this review is to comprehensively discuss TMS‐EEG research in the healthy brain focused on excitability, inhibition, and plasticity following neuromodulatory TMS paradigms from a neurophysiological perspective. A search was conducted in PubMed to identify articles that examined humans and that were written in English and published by September 2018. The search terms were as follows: (TMS OR 'transcranial magnetic stimulation') AND (EEG OR electroencephalog*) NOT (rTMS OR 'repetitive transcranial magnetic stimulation' OR TBS OR 'theta burst stimulation') AND (healthy). The study presents an overview of TMS‐EEG methodology and neurophysiological indices and reviews previous findings from TMS‐EEG in healthy individuals. Furthermore, this review discusses the potential application of TMS‐EEG neurophysiology in the clinical setting to study healthy and diseased brain conditions in the future. Combined TMS‐EEG is a powerful tool to probe and map neural circuits in the human brain noninvasively and represents a promising approach for determining the underlying pathophysiology of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Key points: Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase‐dependent manner.Larger motor‐evoked responses are obtained in a hand muscle when transcranial magnetic stimulation (TMS) is synchronized to the phase of the sensorimotor μ‐rhythm.In this study we further showed that TMS applied at the negative vs. positive peak of the μ‐rhythm is associated with higher absolute amplitude of the evoked EEG potential at 100 ms after stimulation.This demonstrates that cortical responses are sensitive to excitability fluctuation with brain oscillationsOur results indicate that brain state‐dependent stimulation is a new useful technique for the investigation of stimulus‐related cortical dynamics. Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase‐dependent manner. Transcranial magnetic stimulation (TMS) of the human primary motor cortex elicits larger motor‐evoked potentials (MEPs) when applied at the negative vs. positive peak of the sensorimotor μ‐rhythm recorded with EEG, demonstrating that this phase represents a state of higher excitability of the cortico‐spinal system. Here, we investigated the influence of the phase of the μ‐rhythm on cortical responses to TMS as measured by EEG. We tested different stimulation intensities above and below resting motor threshold (RMT), and a realistic sham TMS condition. TMS at 110% RMT applied at the negative vs. positive peak of the μ‐rhythm was associated with higher absolute amplitudes of TMS‐evoked potentials at 70 ms (P70) and 100 ms (N100). Enhancement of the N100 was confirmed with negative peak‐triggered 90% RMT TMS, while phase of the μ‐rhythm did not influence evoked responses elicited by sham TMS. These findings extend the idea that TMS applied at the negative vs. positive peak of the endogenous μ‐oscillation recruits a larger portion of neurons as a function of stimulation intensity. This further corroborates that brain oscillations determine fluctuations in cortical excitability and establishes phase‐triggered EEG‐TMS as a sensitive tool to investigate the effects of brain oscillations on stimulus‐related cortical dynamics. Key points: Oscillatory brain activity coordinates the response of cortical neurons to synaptic inputs in a phase‐dependent manner.Larger motor‐evoked responses are obtained in a hand muscle when transcranial magnetic stimulation (TMS) is synchronized to the phase of the sensorimotor μ‐rhythm.In this study we further showed that TMS applied at the negative vs. positive peak of the μ‐rhythm is associated with higher absolute amplitude of the evoked EEG potential at 100 ms after stimulation.This demonstrates that cortical responses are sensitive to excitability fluctuation with brain oscillationsOur results indicate that brain state‐dependent stimulation is a new useful technique for the investigation of stimulus‐related cortical dynamics. [ABSTRACT FROM AUTHOR]

Objective: Transcranial magnetic stimulation (TMS) produces characteristic deflections in the EEG signal named TMS‐evoked EEG potentials (TEPs), which can be used to assess drug effects on cortical excitability. TMS can also be used to determine the resting motor threshold (RMT) for eliciting a minimal muscle response, as a biomarker of corticospinal excitability. XEN1101 is a novel potassium channel opener undergoing clinical development for treatment of epilepsy. We used TEPs and RMT to measure the effects of XEN1101 in the human brain, to provide evidence that XEN1101 alters cortical excitability at doses that might be used in future clinical trials. Methods: TMS measurements were incorporated in this Phase I clinical trial to evaluate the extent to which XEN1101 modulates TMS parameters of cortical and corticospinal excitability. TEPs and RMT were collected before and at 2‐, 4‐, and 6‐hours post drug intake in a double‐blind, placebo‐controlled, randomized, two‐period crossover study of 20 healthy male volunteers. Results: Consistent with previous TMS investigations of antiepileptic drugs (AEDs) targeting ion channels, the amplitude of TEPs occurring at early (15–55 msec after TMS) and at late (150–250 msec after TMS) latencies were significantly suppressed from baseline by 20 mg of XEN1101. Furthermore, the RMT showed a significant time‐dependent increase that correlated with the XEN1101 plasma concentration. Interpretation: Changes from baseline in TMS measures provided evidence that 20 mg of XEN1101 suppressed cortical and corticospinal excitability, consistent with the effects of other AEDs. These results support the implementation of TMS as a tool to inform early‐stage clinical trials. [ABSTRACT FROM AUTHOR]