Effects of percutaneous cryoablation for renal tumor on overall and split renal function.

PURPOSE: To evaluate retrospectively the influence of percutaneous cryoablation for small renal tumors on total and affected kidney function and risk factors associated with worsening function of the affected kidney. MATERIALS AND METHODS: Between April 2016 and March 2022, 27 patients who underwent cryoablation for small renal tumors at our institution participated in this study, which investigated time-dependent changes in postoperative renal function. We evaluated estimated glomerular filtration rates (eGFRs) and split renal function revealed by scintigraphy using 99 m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before cryoablation and at 1 week, 1 month, and 6 months after cryoablation. Numerous variables were analyzed to assess risk factors for worsening renal function. RESULTS: Baseline eGFR (mean ± standard deviation) was 56.5 ± 23.7 mL/min/1.73 m2 (mean ± SD; range, 20.5-112.5). Mean eGFRs at 1 week, 1 month, and 6 months after cryoablation were 57.4 ± 24.5 (19.1-114.9), 57.1 ± 25.1 (21.5-114.9), and 53.8 ± 23.9 mL/min/1.73 m2 (20.0-107.5), respectively. Changes were statistically insignificant (p = 1.0000, = 0.6749, and = 0.0761, respectively). Regarding split renal function, mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 49.7% ± 6.0% (38.8-63.3%); these rates at 1 week, 1 month, and 6 months after cryoablation were 43.7% ± 8.8 (29.1-70.6%), 46.2% ± 7.7% (32.6-70.3%), and 46.0% ± 8.5% (32.5-67.6%), respectively. Differences from baseline were significant for all periods (p < 0001, < 0001, = 0.0001, respectively). Serum C reactive protein and lactate dehydrogenase at 1 day following cryoablation, tumor's nearness to the collecting system or sinus, and volume of ablated normal renal parenchyma were significantly correlated with decreased contributions of the affected kidney by > 10% after cryoablation. CONCLUSION: Unlike total renal function, affected kidney function could worsen after cryoablation.

A comparative study of the dorsolateral prefrontal cortex targeting approaches for transcranial magnetic stimulation treatment: Insights from the healthy control data.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for medication-resistant depression. Several targeting methods for the left DLPFC have been proposed including identification with resting-state functional magnetic resonance imaging (rs-fMRI) neuronavigation, stimulus coordinates based on structural MRI, or electroencephalography (EEG) F3 site by Beam F3 method. To date, neuroanatomical and neurofunctional differences among those approaches have not been investigated on healthy subjects, which are structurally and functionally unaffected by psychiatric disorders. This study aimed to compare the mean location, its dispersion, and its functional connectivity with the subgenual cingulate cortex (SGC), which is known to be associated with the therapeutic outcome in depression, of various approaches to target the DLPFC in healthy subjects. Fifty-seven healthy subjects underwent MRI scans to identify the stimulation site based on their resting-state functional connectivity and were measured their head size for targeting with Beam F3 method. In addition, we included two fixed stimulus coordinates over the DLPFC in the analysis, as recommended in previous studies. From the results, the rs-fMRI method had, as expected, more dispersed target sites across subjects and the greatest anticorrelation with the SGC, reflecting the known fact that personalized neuronavigation yields the greatest antidepressant effect. In contrast, the targets located by the other methods were relatively close together with less dispersion, and did not differ in anticorrelation with the SGC, implying their limitation of the therapeutic efficacy and possible interchangeability of them.

Real-world retrospective study of repetitive transcranial magnetic stimulation (TMS) treatment for bipolar and unipolar depression using TMS registry data in Tokyo.

Despite the prevalence of empirical practice, evidence supporting the use of repetitive transcranial magnetic stimulation (rTMS) in treating bipolar depression (BD) is sparse compared to that for unipolar depression. Therefore, this study aimed to conduct a retrospective observational analysis using TMS registry data to compare the efficacy of rTMS treatment for BD and unipolar depression. Data from 20 patients diagnosed with unipolar and BD were retrospectively extracted from the TMS registry to ensure age and sex matching. The primary outcomes of this registry study were measured using the 21-item Hamilton Depression Rating Scale (HAM-D21) and Montgomery-Åsberg Depression Rating Scale (MADRS). Analysis did not reveal significant differences between the two groups in terms of depression severity, motor threshold, or stimulus intensity at baseline. Similarly, no significant differences were observed in absolute or relative changes in the total HAM-D21 and MADRS scores. Furthermore, the response and remission rates following rTMS treatment did not differ significantly between groups. The only adverse event reported in this study was scalp pain at the stimulation site; however, the incidence and severity were not significantly different between the groups. In conclusion, this retrospective study, using real-world TMS registry data, suggests that rTMS treatment for BD could be as effective as that for unipolar depression. These findings underscore the need for further validation in prospective randomized controlled trials with larger sample sizes.

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia.

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues' magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility-volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group's nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.gov identifier: NCT02998580) were analyzed using binary logistic regression and conditional inference tree (CIT) modeling. Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. The CIT predicted a higher likelihood of achieving remission for patients with a total score of 19 or lower on the Montgomery-Åsberg Depression Rating Scale, 1 or fewer prior antidepressant treatment failures, and a total score of 23 or higher on the Montreal Cognitive Assessment. Our results indicate that older adults with lower severity of depression, fewer antidepressant treatment failures, and higher global cognition benefit more from current forms of rTMS. The results suggest that there is potentially higher value in using rTMS earlier in the treatment pathway for depression in older adults.

Decreased short-latency afferent inhibition in individuals with mild cognitive impairment: A TMS-EEG study.

TMS combined with EEG (TMS-EEG) is a tool to characterize the neurophysiological dynamics of the cortex. Among the TMS paradigms, short-latency afferent inhibition (SAI) allows the investigation of inhibitory effects mediated by the cholinergic system. The aim of this study was to compare cholinergic function in the DLPFC between individuals with mild cognitive impairment (MCI) and healthy controls (HC) using TMS-EEG with the SAI paradigm. In this study, 30 MCI and 30 HC subjects were included. The SAI paradigm consisted of 80 single pulse TMS and 80 SAI stimulations applied to the left DLPFC. N100 components, global mean field power (GMFP) and total power were calculated. As a result, individuals with MCI showed reduced inhibitory effects on N100 components and GMFP at approximately 100 ms post-stimulation and on ß-band activity at 200 ms post-stimulation compared to HC. Individuals with MCI showed reduced SAI, suggesting impaired cholinergic function in the DLPFC compared to the HC group. We conclude that these findings underscore the clinical applicability of the TMS-EEG method as a powerful tool for assessing cholinergic function in individuals with MCI.

Aberrant heartbeat-evoked potential in schizophrenia.

Self-disturbance is considered a core feature underlying the psychopathology of schizophrenia. Interoception has an important role in the development of a sense of self, leading to increased interest in the potential contribution of abnormal interoception to self-disturbances in schizophrenia. Several neuropsychological studies have demonstrated aberrant interoception in schizophrenia. However, cortical interoceptive processing has not yet been thoroughly investigated. Thus, we sought to examine resting-state heartbeat-evoked potential (HEP) in this population. We hypothesized that patients with schizophrenia would exhibit significant alterations in HEP compared to healthy controls (HCs). In this cross-sectional electroencephalogram (EEG) study, we compared the HEPs between age- and sex-matched groups of patients with schizophrenia and HCs. A 10-min resting-state EEG with eyes closed and an electrocardiogram (ECG) were recorded and analyzed for the time window of 450 ms to 500 ms after an ECG R peak. A positive HEP shift was observed in the frontal-central regions (F [1, 82] = 7.402, p = 0.008, partial η2 = 0.009) in patients with schizophrenia (n = 61) when compared with HCs (n = 31) after adjusting for confounders such as age, sex, and heart rate. A cluster-based correction analysis revealed that the HEP around the right frontal area (Fp2, F4, and F8) showed the most significant group differences (F [1, 82] = 10.079, p = 0.002, partial η2 = 0.021), with a peak at the F4 electrode site (F [1, 82] = 12.646, p < 0.001, partial η2 = 0.069). We observed no correlation between HEP and symptoms in patients with schizophrenia. A positive shift of HEP during the late component could reflect a trait abnormality in schizophrenia. Further research is required to determine the association between the altered cortical interoceptive processing indexed with HEP and self-disturbances in schizophrenia.

Short-Term Effect of Auditory Stimulation on Neural Activities: A Scoping Review of Longitudinal Electroencephalography and Magnetoencephalography Studies.

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing musicians and non-musicians as well as longitudinal studies with musicians. In contrast, studies that address the neural effects of short-term interventions whose duration lasts from minutes to hours are only beginning to be featured. Over the past decade, an increasing body of evidence has shown that short-term auditory interventions evoke rapid changes in neural activities, and oscillatory fluctuations can be observed even in the prestimulus period. In this scoping review, we divided the extracted neurophysiological studies into three groups to discuss neural activities with short-term auditory interventions: the pre-stimulus period, during stimulation, and a comparison of before and after stimulation. We show that oscillatory activities vary depending on the context of the stimuli and are greatly affected by the interplay of bottom-up and top-down modulational mechanisms, including attention. We conclude that the observed rapid changes in neural activitiesin the auditory cortex and the higher-order cognitive part of the brain are causally attributed to short-term auditory interventions.

Development of Artificial Intelligence for Determining Major Depressive Disorder Based on Resting-State EEG and Single-Pulse Transcranial Magnetic Stimulation-Evoked EEG Indices.

Depression is the disorder with the greatest socioeconomic burdens. Its diagnosis is still based on an operational diagnosis derived from symptoms, and no objective diagnostic indicators exist. Thus, the present study aimed to develop an artificial intelligence (AI) model to aid in the diagnosis of depression from electroencephalography (EEG) data by applying machine learning to resting-state EEG and transcranial magnetic stimulation (TMS)-evoked EEG acquired from patients with depression and healthy controls. Resting-state EEG and single-pulse TMS-EEG were acquired from 60 patients and 60 healthy controls. Power spectrum analysis, phase synchronization analysis, and phase-amplitude coupling analysis were conducted on EEG data to extract feature candidates to apply different types of machine learning algorithms. Furthermore, to address the limitation of the sample size, dimensionality reduction was performed in a manner to increase the quality of information by featuring robust neurophysiological metrics that showed significant differences between the two groups. Then, nine different machine learning models were applied to the data. For the EEG data, we created models combining four modalities, including (1) resting-state EEG, (2) pre-stimulus TMS-EEG, (3) post-stimulus TMS-EEG, and (4) differences between pre- and post-stimulus TMS-EEG, and evaluated their performance. We found that the best estimation performance (a mean area under the curve of 0.922) was obtained using receiver operating characteristic curve analysis when linear discriminant analysis (LDA) was applied to the combination of the four feature sets. This study showed that by using TMS-EEG neurophysiological indices as features, it is possible to develop a depression decision-support AI algorithm that exhibits high discrimination accuracy.

A Retrospective Case-Control Study on the Differences in the Effectiveness of Theta-Burst Stimulation Therapy for Depression with and without Antidepressant Medication.

Transcranial magnetic stimulation (TMS) therapy has few side effects and comparable therapeutic effects to antidepressant treatment, but few studies have introduced TMS therapy as an initial treatment for MDD. The objective of this study was to retrospectively compare the clinical outcomes between 50 MDD patients without antidepressants (i.e., TMS monotherapy) and 50 MDD patients with antidepressants plus TMS therapy, matched for age, sex, and depression severity. The presence or absence of antidepressant therapy in first-line treatment was determined via a detailed interview by psychiatrists. The study design was a retrospective observational case-control study using the TMS registry data. The key inclusion criteria were adult patients who met the diagnosis of MDD and received 20-30 sessions of intermittent theta-burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). In this study, the Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome measure. No significant group differences existed in the baseline MADRS total score between the unmedicated and medicated patient groups. Following TMS therapy, no significant group differences in response rate, remission rate, or relative total score change in the MADRS were observed. The main limitations were the retrospective design and the use of registry data as a source. Our findings suggest that TMS monotherapy may be as effective as TMS add-on therapy to antidepressants when used as the first-line therapy for MDD, but randomized controlled trials are needed.

Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS-EEG study.

Major depressive disorder affects over 300 million people globally, with approximately 30% experiencing treatment-resistant depression (TRD). Given that impaired neuroplasticity underlies depression, the present study focused on neuroplasticity in the dorsolateral prefrontal cortex (DLPFC). Here, we aimed to investigate the differences in neuroplasticity between 60 individuals with TRD and 30 age- and sex-matched healthy controls (HCs). To induce neuroplasticity, participants underwent a paired associative stimulation (PAS) paradigm involving peripheral median nerve stimulation and transcranial magnetic stimulation (TMS) targeting the left DLPFC. Neuroplasticity was assessed by using measurements combining TMS with EEG before and after PAS. Both groups exhibited significant increases in the early component of TMS-evoked potentials (TEP) after PAS (P < 0.05, paired t-tests with the bootstrapping method). However, the HC group demonstrated a greater increase in TEPs than the TRD group (P = 0.045, paired t-tests). Additionally, event-related spectral perturbation analysis highlighted that the gamma power significantly increased after PAS in the HC group, whereas it was decreased in the TRD group (P < 0.05, paired t-tests with the bootstrapping method). This gamma power modulation revealed a significant group difference (P = 0.006, paired t-tests), indicating an inverse relationship for gamma power modulation. Our findings underscore the impaired neuroplasticity of the DLPFC in individuals with TRD.

Acetaldehyde-mediated increase in glutamatergic and N-acetylaspartate neurometabolite levels in the midcingulate cortex of ALDH2*1/*2 heterozygous young adults.

BACKGROUND: To elucidate the neurobiology underlying alcohol's effect on the human brain, we examined the acute effects of moderate alcohol administration on levels of glutamatergic neurometabolites and N-acetylaspartate, an amino acid found in neurons, may reflect disordered neuronal integrity. METHODS: Eighteen healthy Japanese participants (7 males/11 females) aged 20-30 years who were heterozygous for an inactive allele of acetaldehyde dehydrogenase-2 (ALDH/*1/*2) were included. Participants underwent an intravenous alcohol infusion using the clamp method at a target blood alcohol concentration (BAC) of 0.50 mg/mL for 90 min within a range of ±0.05 mg/mL. We examined glutamate + glutamine (Glx) and N-acetylaspartate N-acetylaspartylglutamate (NAA) levels in the midcingulate cortex (MCC) using 3 T 1 H-MRS PRESS at baseline, 90 min, and 180 min (i.e., 90 min after alcohol infusion was finished). A two-way repeated-measures analysis of variance was used to assess longitudinal changes in Glx and NAA levels, with time and sex as within- and between-subject factors, respectively. Pearson's correlation coefficients were calculated among neurometabolite levels and BAC or blood acetaldehyde concentration (BAAC). RESULTS: Both Glx (F(2,32) = 8.15, p = 0.004, η2 = 0.15) and NAA (F(2,32) = 5.01, p = 0.04, η2 = 0.07) levels were increased after alcohol injection. There were no sex or time × sex interaction effects observed. NAA levels were positively correlated with BAAC at 90 min (r(13) = 0.77, p = 0.01). There were no associations between neurometabolite levels and BAC. CONCLUSIONS: Both Glx and NAA levels in the MCC increased in response to the administration of moderate concentrations of alcohol. Given positive associations between NAA levels and BAAC and the hypothetical glutamate release via dopamine pathways, the effects of drinking on the MCC in the acute phase may be ascribed to acetaldehyde metabolized from alcohol.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

Associations Between Structural Covariance Network and Antipsychotic Treatment Response in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia is associated with widespread cortical thinning and abnormality in the structural covariance network, which may reflect connectome alterations due to treatment effect or disease progression. Notably, patients with treatment-resistant schizophrenia (TRS) have stronger and more widespread cortical thinning, but it remains unclear whether structural covariance is associated with treatment response in schizophrenia. STUDY DESIGN: We organized a multicenter magnetic resonance imaging study to assess structural covariance in a large population of TRS and non-TRS, who had been resistant and responsive to non-clozapine antipsychotics, respectively. Whole-brain structural covariance for cortical thickness was assessed in 102 patients with TRS, 77 patients with non-TRS, and 79 healthy controls (HC). Network-based statistics were used to examine the difference in structural covariance networks among the 3 groups. Moreover, the relationship between altered individual differentiated structural covariance and clinico-demographics was also explored. STUDY RESULTS: Patients with non-TRS exhibited greater structural covariance compared with HC, mainly in the fronto-temporal and fronto-occipital regions, while there were no significant differences in structural covariance between TRS and non-TRS or HC. Higher individual differentiated structural covariance was associated with lower general scores of the Positive and Negative Syndrome Scale in the non-TRS group, but not in the TRS group. CONCLUSIONS: These findings suggest that reconfiguration of brain networks via coordinated cortical thinning is related to treatment response in schizophrenia. Further longitudinal studies are warranted to confirm if greater structural covariance could serve as a marker for treatment response in this disease.

The relationship between sleep, gut microbiota, and metabolome in patients with depression and anxiety: A secondary analysis of the observational study.

BACKGROUND: Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study. METHODS: Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20). RESULTS: The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group. CONCLUSIONS: Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.

Cost-effectiveness analysis comparing repetitive transcranial magnetic stimulation therapy with antidepressant treatment in patients with treatment-resistant depression in Japan.

Repetitive transcranial magnetic stimulation (rTMS) for patients with treatment-resistant depression (TRD) became covered by the National Health Insurance (NHI) in Japan since 2019. Although the evidence of rTMS for TRD is well established, the cost-effectiveness of rTMS versus antidepressants has not been thoroughly analyzed in Japan. Thus, we aimed to evaluate the cost-effectiveness of rTMS for TRD under the NHI system using a microsimulation model to compare the direct costs and quality-adjusted life years (QALYs). Model inputs of clinical parameters and the utility were derived from published literature. Cost parameters were estimated from the Japanese Claim Database. The robustness of the analyses was evaluated with sensitivity analysis and scenario analysis. The analysis estimated that rTMS increased effectiveness by 0.101QALYs and total cost by ¥94,370 ($689) compared with antidepressant medications. As a result, the incremental cost-effectiveness ratio (ICER) of rTMS was estimated to be ¥935,984 ($6,832)/QALY. In the sensitivity and scenario analyses, ICER did not exceed ¥5 million ($36,496)/QALY as the reference value of the Japanese public cost-effectiveness evaluation system. rTMS therapy for TRD can be a cost-effective treatment strategy compared to antidepressant medication under the NHI system in Japan.

Transcranial magnetic stimulation neurophysiology in patients with non-Alzheimer's neurodegenerative diseases: A systematic review and meta-analysis.

Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.

Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.

Although insulin resistance increases the risk of Alzheimer's disease (AD), the mechanisms remain unclear, partly because no animal model exhibits the insulin-resistant phenotype without persistent hyperglycemia. Here we established an AD model with whole-body insulin resistance without persistent hyperglycemia (APP/IR-dKI mice) by crossbreeding constitutive knock-in mice with P1195L-mutated insulin receptor (IR-KI mice) and those with mutated amyloid precursor protein (AppNL-G-F mice: APP-KI mice). APP/IR-dKI mice exhibited cognitive impairment at an earlier age than APP-KI mice. Since cholinergic dysfunction is a major characteristic of AD, pharmacological interventions on the cholinergic system were performed to investigate the mechanism. Antagonism to a nicotinic acetylcholine receptor α7 (nAChRα7) suppressed cognitive function and cortical blood flow (CBF) response to cholinergic-regulated peripheral stimulation in APP-KI mice but not APP/IR-dKI mice. Cortical expression of Chrna7, encoding nAChRα7, was downregulated in APP/IR-dKI mice compared with APP-KI. Amyloid ß burden did not differ between APP-KI and APP/IR-dKI mice. Therefore, insulin resistance, not persistent hyperglycemia, induces the earlier onset of cognitive dysfunction and CBF deregulation mediated by nAChRα7 downregulation. Our mouse model will help clarify the association between type 2 diabetes mellitus and AD.

Efficacy and moderators of prevention and treatment of delirium with melatonin receptor agonists: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Delirium is a complex and heterogeneous condition that significantly affects patient outcome. This study aimed to conduct a systematic review and meta-analysis to investigate the effects of melatonin and melatonin receptor agonists (MRAs) on delirium prevention and treatment. METHOD: Randomized controlled studies, using MRAs as an intervention and placebo as a control were included. We conducted meta-analyses with random-effects model and trial sequential analysis. RESULTS: A total of 33 studies involving 4850 participants were included. The meta-analysis revealed a significant preventive effect of MRAs on delirium (risk ratio = 0.65, p < 0.01), while no significant therapeutic effect was observed. Additionally, MRAs were associated with a significant reduction in mortality rate (risk ratio = 0.90, p = 0.02) in delirium prevention studies. Furthermore, subgroup analyses revealed that assessment scales and the frequency of delirium detection may be significant moderators of the delirium-preventive efficacy of MRAs. CONCLUSION: This study provides evidence of the potential effects of MRAs in preventing delirium and reducing mortality. Further research is required to elucidate the therapeutic potential of MRAs for delirium and identify specific patient populations that may benefit from this agent.