Search Results (1,350)

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that utilizes magnetic fields to induce cortical electric currents, enabling both the measurement and modulation of neuronal activity. Initially developed as a diagnostic tool, TMS now serves dual roles in clinical neurology, offering insight into neurophysiological dysfunctions and the therapeutic modulation of abnormal cortical excitability. This review examines key TMS outcome measures, including motor thresholds (MT), input–output (I/O) curves, cortical silent periods (CSP), and paired-pulse paradigms such as short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), intracortical facilitation (ICF), long interval cortical inhibition (LICI), interhemispheric inhibition (IHI), and short-latency afferent inhibition (SAI). These biomarkers reflect underlying neurotransmitter systems and can aid in differentiating neurological conditions. Diagnostic applications of TMS are explored in Parkinson’s disease (PD), dystonia, essential tremor (ET), Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Each condition displays characteristic neurophysiological profiles, highlighting the potential for TMS-derived biomarkers in early or differential diagnosis. Therapeutically, repetitive TMS (rTMS) has shown promise in modulating cortical circuits and improving motor and cognitive symptoms. High- and low-frequency stimulation protocols have demonstrated efficacy in PD, dystonia, ET, AD, and MCI, targeting the specific cortical regions implicated in each disorder. Moreover, the successful application of TMS in differentiating and treating AD and MCI underscores its clinical utility and translational potential across all neurodegenerative conditions. As research advances, increased attention and investment in TMS could facilitate similar diagnostic and therapeutic breakthroughs for other neurological disorders that currently lack robust tools for early detection and effective intervention. Moreover, this review also aims to underscore the importance of maintaining standardized TMS protocols. By highlighting inconsistencies and variability in outcomes across studies, we emphasize that careful methodological design is critical for ensuring the reproducibility, comparability, and reliable interpretation of TMS findings. In summary, this review emphasizes the value of TMS as a distinctive, non-invasive approach to probing brain function and highlights its considerable promise as both a diagnostic and therapeutic modality in neurology—roles that are often considered separately. Full article

Background/Objectives: Dementia, characterised by cognitive decline, significantly impacts language abilities. While the risk of dementia increases with age, it often manifests years before clinical diagnosis. Identifying early warning signs is crucial for timely intervention. Previous research has demonstrated that changes in language, such as reduced vocabulary diversity and simpler sentence structures, may be observed in individuals with dementia. This study investigates the potential of linguistic analysis to detect early signs of cognitive decline by examining the writing of Sir Terry Pratchett, a renowned author diagnosed with Posterior Cortical Atrophy (PCA), typically a form of dementia caused by Alzheimer’s disease. Methods: This study analysed 33 Discworld novels by Terry Pratchett, comparing linguistic features before and after a potential turning point identified through analysis of adjective type-token ratios (TTR). Results: A significant decrease in lexical diversity (TTR) was observed for nouns and adjectives in later works. Total wordcount increased, while lexical diversity decreased, suggesting a shift towards simpler language. This shift coincided with a decrease in adjective TTR below a defined threshold, occurring approximately ten years before Pratchett’s formal diagnosis. Conclusions: These findings suggest that subtle changes in linguistic patterns, such as decreased lexical diversity, may precede clinical diagnosis of dementia by a considerable margin. This research highlights the potential of linguistic analysis as a valuable tool for early detection of cognitive decline. Further research is needed to validate these findings in larger cohorts and explore the specific linguistic markers associated with different types of dementia. Full article

Background: Patients with a thin gingival phenotype and a narrow buccal alveolar plate are highly susceptible to periodontal complications during orthodontic expansion. Traditional biomechanics often fail to maintain root control in thin alveolar housing. This report presents two clinical cases illustrating soft- and hard-tissue responses to a novel biomechanical approach, the Bone Protection System (BPS), designed to reduce buccal cortical overload during expansion. Case Presentation: Two adult patients with a thin gingival phenotype assessed by a standardized periodontal probe transparency test and narrow alveolar ridges underwent orthodontic expansion. Patient 1 was treated with the full BPS protocol in both arches. Patient 2 received BPS only in the maxilla, while the mandible was treated conventionally, creating an intra-individual control model under identical systemic conditions. Soft-tissue phenotype and cortical plate response were evaluated clinically and radiographically when applicable. Results: In Patient 1 clinically, the vestibular phenotype showed clear thickening and stabilization. In Patient 2, the maxillary arch treated with BPS exhibited progressive thickening of the vestibular phenotype, whereas the mandible treated conventionally presented thinning and increased translucency—features consistent with buccal compression in thin alveolar bone. No soft- or hard-tissue augmentation procedures were performed in either case. Conclusions: The Bone Protection System may contribute to improved periodontal safety during orthodontic expansion in thin-biotype patients by reducing buccal cortical loading and supporting adaptive soft-tissue and bone responses. Preliminary observations suggests that BPS has potential value for possibly expanding the biological limits of safe tooth movement. Further studies on larger cohorts are warranted. Full article

Traumatic brain injury (TBI) often leads to long-lasting motor deficits, but the underlying cellular mechanisms still remain poorly understood. In this study, we examined glial and neuronal responses after focal cortical aspiration injury of the right hindlimb sensorimotor cortex in adult male rats. This is a model we have previously shown induces persistent gait asymmetry and postural deficits. Immunohistochemical analysis of activated microglia/macrophages (CD11b, IBA-1), astrocytes (GFAP), and neurons (NeuN) was performed bilaterally in the peri-lesional cortex at 3, 7, 14, 21, and 28 days post-injury (n = 3–6 per time point). The injury induced an early, sharply localized increase in CD11b-positive myeloid cells in the injured hemisphere, suggesting an activation of both resident microglia and infiltrating monocyte-derived cell. This was followed by a more sustained IBA-1-positive microglial activation that gradually extended contralaterally. Astrocytic activation showed a delayed but prolonged profile, rising ipsilaterally within the first week, peaking around two weeks, and becoming bilaterally elevated by four weeks. Sham-operated animals showed only basal glial immunoreactivity without signs of hypertrophy or reactive morphology at any time point. NeuN immunoreactivity remained stable across timepoints, suggesting preservation of neuronal soma labeling without evidence of overt secondary neuronal loss. These findings reveal a staged and spatially distinct glial response to focal cortical injury, with early myeloid activation, prolonged microglial reactivity, and delayed bilateral astrogliosis. Together, these findings are consistent with the possibility that persistent motor deficits after focal TBI arise from both primary tissue loss within the lesion core and peri-lesional glial remodeling, highlighting glial–neuronal interactions as a potential therapeutic target. Full article

Fucoidan, a complex sulfated polysaccharide derived from marine brown seaweeds, exhibits broad biological activities, including anticoagulant, antitumor, antiviral, anti-inflammatory and lipid-lowering effects. Fucoidan confers neuroprotection in animal models of a broad spectrum of brain disorders such as Parkinson’s disease (PD) and depression. However, the effect of fucoidan on gut-derived neuroinflammation and associated behavioral changes has been scarcely investigated. In comparison to fucoidan from other brown seaweeds, that from Fucus vesiculosus exhibited a better neuroprotective effect in vivo and more potent radical scavenging activity in vitro. Fucoidan from Laminaria japonica ameliorates behavioral disorders related to acute ulcerative colitis (UC) in aged mice. It is of interest to assess the effects of fucoidan administration on intestinal and brain inflammation in the acute colitis mouse model. Fucoidan treatment ameliorated DSS-induced intestinal pathology, reduced the inflammatory mediator expression in the gut and brain, and activated intestinal macrophages and cortical microglia in the UC mice. It also protected the intestinal mucosal barrier and blood–brain barrier as well as prevented neuronal damage, while alleviating anxiety-like behavior in UC mice. These results suggest fucoidan supplementation may help prevent brain disorders, such as depression and PD, potentially involving gut–brain axis-related mechanisms, as fucoidan suppresses gut-derived neuroinflammation. Full article

Background and Clinical Significance: Focal hemorrhagic severity associated with posterior convexity pial brain arteriovenous malformation (AVM) cases can be exacerbated by hemodynamic stress focusing on focal areas of architectural weakness and by superficial venous outflow being restricted by non-redundant superficial venous drainage. This clinical case report exemplifies how bedside neurologic localization and angioarchitectural characteristics can inform the selection of microsurgical approaches for the treatment of ruptured AVMs that are directed at reducing hemorrhage recurrence risk through corridors based on rupture location. Case Presentation: An otherwise healthy young adult male (modified Rankin scale [mRS] pre-morbid = 0) initially presented with a thunderclap headache, emesis, photophobia, decreased level of consciousness (admitted Glasgow Coma Score [GCS] = 11; E3V3M5), and subsequent deficits including left-sided pyramidal weakness, visual field loss, and visuo-spatial neglect. A non-contrast computed tomogram (CT) confirmed an intraparenchymal hemorrhage (ICH) located within the right hemisphere’s posterior lobe. Angiographic evaluation of this AVM with catheter injection and three-dimensional reconstruction revealed a compact right occipital posterior convexity pial AVM (nidus 8 × 3 mm) supplied by distal cortical branches of the right middle cerebral artery (MCA); all blood draining from the nidus was directed to a single cortical vein which then drained into the superior sagittal sinus; there were two additional intranidal saccular aneurysms (approximately 3 × 2 mm and 3 × 3 mm). Because of the acute worsening secondary to ICH and because all venous drainage was superficial-only, a single-stage approach was selected given the urgency: decompressive evacuation of the hematoma via a corridor to the site of the AVM, followed by microsurgical removal of the AVM. The removal of the AVM was accomplished in a feeder-first, vein-last sequence, and en-passage arteries and parasagittal bridging veins were preserved throughout the procedure. Additionally, the two intranidal aneurysms identified as potential weak points during progressive devascularization of the AVM were specifically treated during the removal procedure. Following the successful removal of the AVM, the patient experienced a rapid recovery and returned to a nearly premorbid state of functioning, excepting a persistent small area of quadrantanopia. Conclusions: Rupture of posterior convexity AVMs may result in increased hemorrhagic severity due to localized architectural weaknesses in addition to the overall size of the AVM nidus. By correlating neurological findings, the topography of the hemorrhage, and angioarchitectural features early after rupture, emergency decisions regarding management can be better informed. The application of a hematoma-corridor, feeder-first/vein-last microsurgical approach for the treatment of such AVMs can achieve definitive curative results while minimizing damage to posterior cortical regions. Full article

Brain–computer interface-based (BCI) training induces neural plasticity and promotes motor recovery in stroke patients by pairing movement intentions with congruent electrical stimulation of the affected limb, eliciting somatosensory afferent feedback. However, this training can potentially be refined further to enhance rehabilitation outcomes. It is not known how specific the afferent feedback needs to be with respect to the efferent activity from the brain. This study investigated how corticospinal excitability, a marker of neural plasticity, was modulated by four types of BCI-like interventions that varied in the specificity of afferent feedback relative to the efferent activity. Fifteen able-bodied participants performed four interventions: (1) wrist extensions paired with radial nerve peripheral electrical stimulation (PES) (matching feedback), (2) wrist extensions paired with ulnar nerve PES (non-matching feedback), (3) wrist extensions paired with sham radial nerve PES (no feedback), and (4) palmar grasps paired with radial nerve PES (partially matching feedback). Each intervention consisted of 100 pairings between visually cued movements and PES. The PES was triggered based on the peak of maximal negativity of the movement-related cortical potential associated with the visually cued movement. Before, immediately after, and 30 min after the intervention, transcranial magnetic stimulation-elicited motor-evoked potentials were recorded to assess corticospinal excitability. Only wrist extensions paired with radial nerve PES significantly increased the corticospinal excitability with 57 ± 49% and 65 ± 52% immediately and 30 min after the intervention, respectively, compared to the pre-intervention measurement. In conclusion, maximizing the induction of neural plasticity with an associative BCI requires that the afferent feedback be precisely matched to the efferent brain activity. Full article

Background and Clinical Significance: This report presents the case of a 33-year-old female with recurrent miscarriage, investigated for an adrenal cortical adenoma characterized by autonomous secretion of 17-hydroxyprogesterone (17-OHP). The findings challenge the established diagnostic paradigm, which predominantly attributes elevated serum 17-OHP to congenital adrenal hyperplasia (CAH) or non-classical CAH (NCCAH). Case Presentation: The patient was found to have elevated serum 17-OHP and a 2 cm left adrenal mass. Normal testosterone and precursor levels, along with whole-exome sequencing (WES), argued against a diagnosis of non-classical 21-hydroxylase deficiency (NC-21OHD). An ACTH stimulation test elicited a mild-to-moderate rise in 17-OHP, while adrenal venous sampling (AVS) confirmed marked lateralization of 17-OHP hypersecretion to the left side. Postoperative normalization of 17-OHP levels further supported the diagnosis of a 17-OHP-secreting tumor. Histopathological analysis identified tumor regions with non-uniformly high expression of CYP17A1 and CYP21A2. Preliminary transcriptomic profiling revealed that differentially expressed genes (DEGs) were enriched in microRNA-related and PI3K-Akt signaling pathways. Conclusions: This paradigm-shifting case indicates that, in addition to 21OHD, a 17-OHP-hypersecreting adrenal adenoma should be considered in the differential diagnosis of elevated 17-OHP. The integration of multimodal diagnostic techniques, particularly AVS, is valuable for localizing hormonally active tumors. Preliminary mechanistic insights suggest a potential role for epigenetic dysregulation in the pathogenesis of this tumor type. Full article

Background/Objectives: Post-traumatic epileptogenesis is a frequent and clinically relevant consequence of traumatic brain injury (TBI), often contributing to worsened neurological and functional outcomes. In patients experiencing early post-injury seizures, rehabilitative strategies that support recovery while considering increased epileptogenic risk are needed. This case study explores the potential benefits of combining neurofeedback (NFB) with motor therapy on cognitive and motor recovery. Methods: A patient hospitalized for severe TBI who experienced an acute symptomatic seizure in the early post-injury phase underwent baseline quantitative EEG (qEEG), neuromotor, functional, and neuropsychological assessments. The patient then completed a three-week rehabilitation program (five days/week) including 30 sensorimotor rhythm (SMR) NFB sessions (35 min each) combined with daily one-hour motor therapy. qEEG and clinical assessments were repeated post-intervention and at 6-month follow-up. Results: Post-intervention qEEG showed significant reductions in Delta and Theta power, reflecting decreased cortical slowing and enhanced neural activation. Relative power analysis indicated reduced Theta activity and Alpha normalization, suggesting improved cortical stability. Increases were observed in Beta and High-beta activity, alongside significant reductions in the Theta/Beta ratio, consistent with improved attentional regulation. Neuropsychological outcomes revealed reliable improvements in global cognition, memory, and visuospatial abilities, mostly maintained or enhanced at follow-up. Depressive and anxiety symptoms decreased markedly. Motor and functional assessments demonstrated meaningful improvements in motor performance, coordination, and functional independence. Conclusions: Findings suggest that integrating NFB with motor therapy may support recovery processes and be associated with sustained neuroplastic changes in the early post-injury phase after TBI, a condition associated with elevated risk for post-traumatic epilepsy. Full article

Background: Deep brain stimulation (DBS) is increasingly understood as a precision-oriented neuromodulation therapy capable of influencing distributed basal ganglia–thalamo–cortical and cerebellothalamic networks. Although its symptomatic benefits in Parkinson’s disease, essential tremor, and dystonia are well established, the extent to which DBS supports motor learning, adaptive plasticity, and participation in rehabilitation remains insufficiently defined. Traditional interpretations of DBS as a focal or lesion-like intervention are being challenged by electrophysiological and imaging evidence demonstrating multiscale modulation of circuit dynamics. Objectives and methods: DBS may enhance rehabilitation outcomes by stabilizing pathological oscillations and reducing moment-to-moment variability in motor performance, thereby enabling more consistent task execution and more effective physiotherapy, occupational therapy, and speech–language interventions. However, direct comparative evidence demonstrating additive or synergistic effects of DBS combined with rehabilitation remains limited. As a result, this potential is not fully realized in clinical practice due to interindividual variability, limited insight into how individual circuit architecture shapes therapeutic response, and the limited specificity of current connectomic biomarkers for predicting functional gains. Results: Technological advances such as tractography-guided targeting, directional leads, sensing-enabled devices, and adaptive stimulation are expanding opportunities to align neuromodulation with individualized circuit dysfunction. Despite these developments, major conceptual and empirical gaps persist. Few controlled studies directly compare outcomes with versus without structured rehabilitation following DBS. Heterogeneity in therapeutic response and rehabilitation access further complicates the interpretation of outcomes. Clarifying these relationships is essential for developing precision-informed frameworks that integrate DBS with rehabilitative strategies, recognizing that current connectomic and physiological biomarkers remain incompletely validated for predicting functional outcomes. Conclusions: This review synthesizes mechanistic, imaging, and technological evidence to outline a network-informed perspective of DBS as a potential facilitator of rehabilitation-driven functional improvement and identifies priorities for future research aimed at optimizing durable functional restoration. Full article

Background: The current biomarker classification system does not fully explain the increased prevalence of both Alzheimer’s disease (AD) and vascular risk factors for AD—such as diabetes and hypertension--among African Americans (AAs) compared to White participants. Research on cognitive aging has traditionally focused on how declines in cortical and hippocampal regions influence cognition. However, tau pathology emerges decades before amyloid pathology, initially appearing in the brainstem, particularly in the locus coeruleus (LC), the primary source of the brain’s norepinephrine (NE). Further, postmortem studies suggest that the loss of LC neurons is a better predictor of AD symptom severity than amyloid-beta/neurofibrillary tangle pathology in any other brain region. Methods: Our decade-long studies in humans using a norepinephrine transporter (NET)-selective radiotracer ([¹¹C]MRB) have demonstrated that LC is uniquely vulnerable to aging and stress. In this retrospective study, regression slopes with age (RSAs) for regional NET availability were compared across groups and tested for statistical significance. Results: In our primary analysis, higher NET availability was observed in AAs (N = 14; 7 males aged 23–49), particularly at younger ages, as compared to White (N = 16; 11 males aged 24–55) participants. Our preliminary data also suggest that the rate of decline in NET availability is faster in AAs, with a potential trend toward a more pronounced effect in AA males as compared to White males (e.g., in the left thalamus, RSA was −3.03%/year [95%CI: −5.80% to 1.19%] for AA males vs. RSA = −0.14 for White males [95%CI: −0.79% to 0.47%]. Additionally, in the right anterior cingulate cortex, RSA was −3.4%/year [95%CI: −4.6% to −1.4%] for AA males, compared to RSA = 0.3%/year [95%CI: 0.04% to 1.03%] for White males). Conclusions: This report reveals that NET availability (measured with [¹¹C]MRB) can serve as a biomarker to index the function of the LC-NE system and that the fast-decline rate of NET in AAs implicates a potential molecular mechanism underlying health disparities observed in the disproportionate AD prevalence. Full article

Functional Near-Infrared Spectroscopy (fNIRS), a non-invasive neuroimaging technique, has demonstrated unique advantages in linguistic research in recent years. By monitoring changes in the concentrations of oxygenated and deoxygenated hemoglobin during cortical activation, fNIRS provides new insights into the mechanisms underlying language processing. Its ecological validity and high compatibility enable seamless integration into real-world environments, minimizing interference and ensuring the authenticity of the collected data. In the realm of linguistics, fNIRS has been applied to studies on language perception, function, acquisition, cross-linguistic processing, and the assessment of language disorders, revealing the intricate mechanisms of language processing and showcasing its potential for clinical applications. This article reviews the latest advancements in the utilization of fNIRS in linguistic research, aiming to provide valuable references for researchers and to foster deeper exploration and innovative development in this field. Meanwhile, this article systematically examines the limitations of fNIRS in current research, provides a critical assessment of its methodological and applicative value, and, on this basis, outlines future directions and potential breakthroughs for this technology in the field of language research. Full article

Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal conditions and at varying levels of oxidative stress. Male SHRSP rats were assigned to five experimental groups and subjected to RNS at different frequencies, with infusions of vehicle, tempol, tempol plus catalase (tem + cat), diethyldithiocarbamic acid (DETC), or L-nitro-arginine methyl ester (L-NAME) at the renal cortico-medullary border (CMB). Regional blood perfusion of the renal cortex and medulla (CBP and MBP, respectively) was assessed using Laser-Doppler flowmetry. RNS significantly reduced CBP and MBP by 43 ± 8% and 23 ± 4%, respectively, at 8 Hz. Co-infusion of tempol plus catalase significantly attenuated the RNS-induced reductions in both CBP and MBP. Similarly, DETC infusion mitigated RNS-induced decreases in CBP and MBP. In contrast, tempol alone and L-NAME did not protect against the RNS-induced under-perfusion of the renal cortex and medulla. The results suggest that simultaneous removal of superoxide anion and hydrogen peroxide (H₂O₂) can alleviate the reduction in renal blood perfusion caused by RNS, emphasizing a crucial role for H₂O₂ in renal hemodynamic regulation. Interestingly, DETC, which is expected to elevate superoxide anion levels, also mitigated RNS-induced under-perfusion, suggesting the presence of a potentially novel indirect protective mechanism that warrants further investigation. Full article

Background/Objectives: Biopsychosocial pain neuroscience education (PNE) has recently gained attention in preparing patients for surgery. PNE is expected to influence pain coping strategies and descending nociceptive inhibition. The goal of this study was to compare cortical evoked responses during experimental pain processing using a conditioned pain modulation (CPM) paradigm between patients receiving perioperative PNE (PPNE) or perioperative biomedical back school education (PBSE). Methods: This predefined EEG subgroup analysis included only participants with complete EEG recordings at baseline and 6 weeks. Of these, twenty-three patients with low back-related leg pain, scheduled for lumbar spine surgery, were randomized to either two sessions of PPNE or two sessions of PBSE. All patients were stimulated electrically at the median nerve of the symptomatic side and the sural nerve of the symptomatic and non-symptomatic side before and 6 weeks after the educational sessions, while evoked potentials were recorded by electroencephalography (EEG). Subsequently, this protocol was repeated during the application of the CPM paradigm by immersing the hand contralateral to the symptomatic side into cold water. Results: A significant decrease in the amplitude of the waveforms during CPM was found compared to the waveforms before CPM at the non-symptomatic sural nerve. No significant differences were found at the other test locations. For the waveforms of the CPM effect (subtracted waveforms), no significant treatment effects were revealed between the PPNE and PBSE groups. Conclusions: These exploratory findings suggest that PPNE was not associated with differential modulation of EEG evoked potentials during CPM compared with PBSE at 6 weeks post-surgery. Full article

Fractal geometry offers a mathematical framework to quantify the complexity of brain structure and function. The fractal dimension (FD) captures self-similarity and irregularity across spatial and temporal scales, surpassing the limits of traditional Euclidean metrics. In neuroscience, FD serves as a key descriptor of the brain’s hierarchical organization—from dendritic arborization and cortical folding to neural dynamics measured by diverse neuroimaging techniques. This review summarizes theoretical foundations and methodological advances in FD estimation, including the box-counting approach for imaging, and Higuchi’s and Katz’s algorithms for electrophysiological data, addressing reliability and reproducibility issues. In addition, we illustrate how fractal analysis characterizes brain complexity in health and disease. Clinical applications include detecting white matter alterations in multiple sclerosis, atypical maturation in intrauterine growth restriction, reduced cortical complexity in Alzheimer’s disease, and altered neuroimaging patterns in schizophrenia. Emerging evidence highlights FD’s potential for distinguishing consciousness states and quantifying neural integration and differentiation. Bridging mathematics, physics, and neuroscience, fractal analysis provides a quantitative lens on the brain’s multiscale organization and pathological deviations. FD thus stands as both a theoretical descriptor and a translational biomarker whose standardization could advance precision diagnostics and understanding of neural dynamics. Full article