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34 pages, 2164 KiB  
Review
Non-Drug and Non-Invasive Therapeutic Options in Alzheimer’s Disease
by Alina Simona Șovrea, Adina Bianca Boșca, Eleonora Dronca, Anne-Marie Constantin, Andreea Crintea, Rada Suflețel, Roxana Adelina Ștefan, Paul Andrei Ștefan, Mădălin Mihai Onofrei, Christoph Tschall and Carmen-Bianca Crivii
Biomedicines 2025, 13(1), 84; https://doi.org/10.3390/biomedicines13010084 - 1 Jan 2025
Viewed by 107
Abstract
Despite the massive efforts of modern medicine to stop the evolution of Alzheimer’s disease (AD), it affects an increasing number of people, changing individual lives and imposing itself as a burden on families and the health systems. Considering that the vast majority of [...] Read more.
Despite the massive efforts of modern medicine to stop the evolution of Alzheimer’s disease (AD), it affects an increasing number of people, changing individual lives and imposing itself as a burden on families and the health systems. Considering that the vast majority of conventional drug therapies did not lead to the expected results, this review will discuss the newly developing therapies as an alternative in the effort to stop or slow AD. Focused Ultrasound (FUS) and its derived Transcranial Pulse Stimulation (TPS) are non-invasive therapeutic approaches. Singly or as an applied technique to change the permeability of the blood–brain–barrier (BBB), FUS and TPS have demonstrated the benefits of use in treating AD in animal and human studies. Adipose-derived stem Cells (ADSCs), gene therapy, and many other alternative methods (diet, sleep pattern, physical exercise, nanoparticle delivery) are also new potential treatments since multimodal approaches represent the modern trend in this disorder research therapies. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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<p>New alternative non-drug therapeutic options for AD.</p>
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<p>FUS application bioeffects.</p>
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<p>Biological effects of TPS.</p>
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<p>Positive and negative effects of HBOT.</p>
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20 pages, 3795 KiB  
Article
Exploring Machine Learning Classification of Movement Phases in Hemiparetic Stroke Patients: A Controlled EEG-tDCS Study
by Rishishankar E. Suresh, M S Zobaer, Matthew J. Triano, Brian F. Saway, Parneet Grewal and Nathan C. Rowland
Brain Sci. 2025, 15(1), 28; https://doi.org/10.3390/brainsci15010028 - 29 Dec 2024
Viewed by 387
Abstract
Background/Objectives: Noninvasive brain stimulation (NIBS) can boost motor recovery after a stroke. Certain movement phases are more responsive to NIBS, so a system that auto-detects these phases would optimize stimulation timing. This study assessed the effectiveness of various machine learning models in identifying [...] Read more.
Background/Objectives: Noninvasive brain stimulation (NIBS) can boost motor recovery after a stroke. Certain movement phases are more responsive to NIBS, so a system that auto-detects these phases would optimize stimulation timing. This study assessed the effectiveness of various machine learning models in identifying movement phases in hemiparetic individuals undergoing simultaneous NIBS and EEG recordings. We hypothesized that transcranial direct current stimulation (tDCS), a form of NIBS, would enhance EEG signals related to movement phases and improve classification accuracy compared to sham stimulation. Methods: EEG data from 10 chronic stroke patients and 11 healthy controls were recorded before, during, and after tDCS. Eight machine learning algorithms and five ensemble methods were used to classify two movement phases (hold posture and reaching) during each of these periods. Data preprocessing included z-score normalization and frequency band power binning. Results: In chronic stroke participants who received active tDCS, the classification accuracy for hold vs. reach phases increased from pre-stimulation to the late intra-stimulation period (72.2% to 75.2%, p < 0.0001). Late active tDCS surpassed late sham tDCS classification (75.2% vs. 71.5%, p < 0.0001). Linear discriminant analysis was the most accurate (74.6%) algorithm with the shortest training time (0.9 s). Among ensemble methods, low gamma frequency (30–50 Hz) achieved the highest accuracy (74.5%), although this result did not achieve statistical significance for actively stimulated chronic stroke participants. Conclusions: Machine learning algorithms showed enhanced movement phase classification during active tDCS in chronic stroke participants. These results suggest their feasibility for real-time movement detection in neurorehabilitation, including brain–computer interfaces for stroke recovery. Full article
(This article belongs to the Special Issue The Application of EEG in Neurorehabilitation)
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<p>(<b>A</b>) A total of 10 participants with chronic stroke and 11 healthy controls were randomized into active and sham stimulation groups. (<b>B</b>) The participants were fitted with EEG electrodes and HD-tDCS delivering anodal stimulation to the ipsilesional side (contralateral to the motor deficit); for healthy participants, laterality was randomized. (<b>C</b>) During the stimulation phase, the participants performed a VR motor task involving reaches toward a virtual blue sphere target (3 cm radius) placed 0.3–0.5 m away. The task had three steps: hold, prep (Cue), and move. An example VR scene is shown. (<b>D</b>) Sham participants received 30 s of ramp-up current, then no stimulation, while active stimulation included 30 s ramp-up followed by 20 min of stimulation. Twelve reaches were performed at each time period. EEG was recorded at pre, 5 min (intra5), 15 min (intra15), and post-stimulation (post). (<b>E</b>) The raw EEG signal was recorded from all channels. After normalization, the power spectral density was calculated and binned across frequency bands to complete feature extraction. (<b>F</b>) Thirteen ML models were trained using 70% of the pre-stim data and then tested on 30% of the pre-stim data and 100% of the data from other time periods. This was performed to simulate ex vivo training of an onboard BCI.</p>
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<p>(<b>A</b>) Classification of disease state (healthy versus chronic stroke) using all frequencies from 1 to 50 Hz and all electrodes. Although most algorithms detected differences prior to stimulation, LDA was not affected. (<b>B</b>) Mean accuracies. (<b>C</b>) To account for baseline differences at the pre-stimulation time periods, we normalized the accuracies to the pre-stimulation accuracy for each group. Asterisks (*) indicate a significant difference between active and sham groups. We observed a significantly increased classification accuracy for the active stim group at the intra5 and post-stimulation time periods, with accuracies converging at intra15. Values in parentheses represent the number of algorithms per group at each time period.</p>
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<p>(<b>A</b>) Hold versus reach movement classification using all frequencies of 1–50 Hz and all electrodes. In the CS active group, the classification accuracy increased after stimulation and peaked at intra15 (*, asterisk). Furthermore, the accuracy at this time period was significantly higher than in the CS sham group at the same time (†, cross). (<b>B</b>) Movement classification was higher at intra15 than pre in the CS active group. (<b>C</b>) Movement classification was higher for intra15 CS active than intra15 CS sham. Values in parentheses represent the number of algorithms per group at each time period. (<b>D</b>) Mean accuracies. Values in parentheses represent the number of algorithms per group at each time period. (<b>E</b>) We observed a tradeoff between the training time and accuracy, as LDA produced the highest accuracy with a short training time compared to the other models with the exception of DT, which obtained a slightly higher mean accuracy but required the longest training time.</p>
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<p>(<b>A</b>) Hold versus reach movement classification using all frequencies of 1–50 Hz and all electrodes by the frequency band used (delta through gamma) in CS active participants only. Gamma PSD alone produced the highest classification accuracy for most models, although this was not statistically significant. (<b>B</b>) Mean accuracies. (<b>C</b>) When comparing the classification accuracy over time by band, we observe a broadband increase in the accuracy, seen in all bands at intra15. We also observe some differences in the band response, highlighted here using colored asterisks corresponding to each band. Values in parentheses represent the number of algorithms per individual frequency band at each time period. (<b>D</b>) When aggregating algorithms by method, we observed that ensemble methods (such as global voting, or hard voting) resolved frequency bands more so than other models, although this was not significant. Dimensionality reduction (LDA) and regression (LR) methods outperformed the others. Values in parentheses represent the number of algorithms per method at each time period.</p>
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<p>(<b>A</b>) Hold versus reach movement classification using C3 or C4 electrodes and all frequencies of 1–50 Hz. Number of asterisks (*) represents significance level between contra- and ipsi-lesional accuracy. Here, we investigated the effect of recording electrode lesion laterality. We observed that contralesional classification accuracy significantly decreases during stimulation compared to ipsilesional accuracy in CS active participants; this is not seen in any of the other groups. Values in parentheses represent the number of algorithms per group at each time period. (<b>B</b>) Mean accuracies.</p>
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26 pages, 1809 KiB  
Review
Brain Stimulation Techniques in Research and Clinical Practice: A Comprehensive Review of Applications and Therapeutic Potential in Parkinson’s Disease
by Ata Jahangir Moshayedi, Tahmineh Mokhtari and Mehran Emadi Andani
Brain Sci. 2025, 15(1), 20; https://doi.org/10.3390/brainsci15010020 - 27 Dec 2024
Viewed by 373
Abstract
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods [...] Read more.
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), transcranial focused ultrasound stimulation (tFUS), and transcutaneous vagus nerve stimulation (tVNS), as well as invasive approaches like deep brain stimulation (DBS). We explore the efficacy and safety profiles of these techniques in alleviating both motor impairments, such as bradykinesia and rigidity, and non-motor symptoms, including cognitive decline, depression, and impulse control disorders. Current findings indicate that while non-invasive techniques present a favorable safety profile and are effective for milder symptoms, invasive methods like DBS provide significant relief for severe cases that are unresponsive to other treatments. Future research is needed to optimize stimulation parameters, establish robust clinical protocols, and expand the application of these technologies across various stages of PD. This review underscores the potential of brain stimulation as a vital therapeutic tool in managing PD, paving the way for enhanced treatment strategies and improved patient outcomes. Full article
(This article belongs to the Special Issue Noninvasive Neuromodulation Applications in Research and Clinics)
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<p>The reviewed paper analyses: (<b>A</b>) review Prisma diagram, and (<b>B</b>) the papers based on publishers.</p>
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<p>Timeline of brain stimulation methods for the treatment of PD.</p>
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<p>Brain regions relevant to Parkinson’s Disease (PD). The areas highlighted include Substantia Nigra (01), Dopamine Pathway (02), Putamen (Striatum; 03), and Caudate Nucleus (Striatum; 04). The figure illustrates the five stages of PD, along with brain stimulation methods employed for PD patients.</p>
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14 pages, 5683 KiB  
Communication
The Thermal Ablation with MRgFUS: From Physics to Oncological Applications
by Mario Leporace, Ferdinando F. Calabria, Roberto Siciliano, Carlo Capalbo, Dimitrios K. Filippiadis and Roberto Iezzi
Cancers 2025, 17(1), 36; https://doi.org/10.3390/cancers17010036 - 26 Dec 2024
Viewed by 288
Abstract
The growing interest in minimal and non-invasive therapies, especially in the field of cancer treatment, highlights a significant shift toward safer and more effective options. Ablative therapies are well-established tools in cancer treatment, with known effects including locoregional control, while their role as [...] Read more.
The growing interest in minimal and non-invasive therapies, especially in the field of cancer treatment, highlights a significant shift toward safer and more effective options. Ablative therapies are well-established tools in cancer treatment, with known effects including locoregional control, while their role as modulators of the systemic immune response against cancer is emerging. The HIFU developed with magnetic resonance imaging (MRI) guidance enables treatment precision, improves real-time procedural control, and ensures accurate outcome assessment. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) induces deep coagulation necrosis within an elliptical focal area, effectively encompassing the entire tumor site and allowing for highly targeted radical ablation. The applications of MRgFUS in oncology are rapidly expanding, offering pain relief and curative treatment options for bone metastatic lesions. Additionally, the MRgFUS plays an effective role in targeted optional therapies for early prostate and breast cancers. Emerging research also focuses on the potential uses in treating abdominal cancers and harnessing capabilities to stimulate immune responses against tumors or to facilitate the delivery of anticancer drugs. This evolving landscape presents exciting opportunities for improving patient outcomes and advancing cancer treatment methodologies. In neuro-oncology, MRgFUS utilizes low-intensity focused ultrasound (LIFU) along with intravenous microbubbles to open the blood-brain barrier (BBB) and enhance the intra-tumoral delivery of chemotherapy drugs. Full article
(This article belongs to the Special Issue Medical Imaging and Artificial Intelligence in Cancer)
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<p>The diagram illustrates an MRI scanner equipped with a high-intensity focused ultrasound (HIFU) transducer on the patient table. It showcases the configuration of the MR-guided Focused Ultrasound (MRgFUS) system, which includes an integrated focused ultrasound unit within the MRI bed. Patients are positioned carefully to ensure that the area of interest aligns directly above the FUS transducer. The concave transducer, submerged in degassed water and using a coupling gel pad, effectively transmits acoustic waves through the patient’s body. This multi-element ultrasonic transducer focuses ultrasound waves on the targeted area (focal zone), generating heat that leads to precise tissue ablation via necrosis. This advanced procedure is performed while the patient is inside the bore-MRI, always adhering to strict treatment planning protocols.</p>
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<p>Schematic drawing of the sonication and thermal cytotoxic effects of the HIFU in the focal zone. The necrotic post-ablative lesions are elliptical; multiple sonications without gaps are necessary to target the entire lesion and achieve radical tumor ablation.</p>
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<p>The thermo-mechanical effect of HIFU can be exploited to improve drug distribution and absorption by promoting the release of anticancer molecules encapsulated in a carrier (liposome) within the target tumor site.</p>
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<p>HIFU ablation can induce an immune response. The generation of tumor debris in situ increases the circulation of tumor-associated antigens. This activates the immune response mediated by the interaction between antigen-presenting cells (APCs) and T lymphocytes (T cells) and will target cancer cells that expose that specific antigen. The activated T lymphocytes can infiltrate the tumor site and attack tumor cells by passing through the systemic circulation.</p>
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3 pages, 428 KiB  
Editorial
Emerging Trends in Non-Invasive Brain Stimulation: The New Kids on the Block
by Andre R. Brunoni, Paul E. Croarkin and Lais B. Razza
Biomedicines 2025, 13(1), 14; https://doi.org/10.3390/biomedicines13010014 - 25 Dec 2024
Viewed by 292
Abstract
In the Sustainable Development Goals of the United Nations for 2030, mental health has been identified as a global priority, emphasizing the need to reduce the prevalence, morbidity, and premature mortality associated with mental disorders [...] Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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<p>Established and newer forms of non-invasive brain stimulation.</p>
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19 pages, 1342 KiB  
Article
The Modulatory Effects of Transcranial Alternating Current Stimulation on Brain Oscillatory Patterns in the Beta Band in Healthy Older Adults
by Kenya Morales Fajardo, Xuanteng Yan, George Lungoci, Monserrat Casado Sánchez, Georgios D. Mitsis and Marie-Hélène Boudrias
Brain Sci. 2024, 14(12), 1284; https://doi.org/10.3390/brainsci14121284 - 20 Dec 2024
Viewed by 705
Abstract
Background: In the last few years, transcranial alternating current stimulation (tACS) has attracted attention as a promising approach to interact with ongoing oscillatory cortical activity and, consequently, to enhance cognitive and motor processes. While tACS findings are limited by high variability in young [...] Read more.
Background: In the last few years, transcranial alternating current stimulation (tACS) has attracted attention as a promising approach to interact with ongoing oscillatory cortical activity and, consequently, to enhance cognitive and motor processes. While tACS findings are limited by high variability in young adults’ responses, its effects on brain oscillations in older adults remain largely unexplored. In fact, the modulatory effects of tACS on cortical oscillations in healthy aging participants have not yet been investigated extensively, particularly during movement. This study aimed to examine the after-effects of 20 Hz and 70 Hz High-Definition tACS on beta oscillations both during rest and movement. Methods: We recorded resting state EEG signals and during a handgrip task in 15 healthy older participants. We applied 10 min of 20 Hz HD-tACS, 70 Hz HD-tACS or Sham stimulation for 10 min. We extracted resting-state beta power and movement-related beta desynchronization (MRBD) values to compare between stimulation frequencies and across time. Results: We found that 20 Hz HD-tACS induced a significant reduction in beta power for electrodes C3 and CP3, while 70 Hz did not have any significant effects. With regards to MRBD, 20 Hz HD-tACS led to more negative values, while 70 Hz HD-tACS resulted in more positive ones for electrodes C3 and FC3. Conclusions: These findings suggest that HD-tACS can modulate beta brain oscillations with frequency specificity. They also highlight the focal impact of HD-tACS, which elicits effects on the cortical region situated directly beneath the stimulation electrode. Full article
(This article belongs to the Special Issue The Application of EEG in Neurorehabilitation)
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<p>Schematic of the experimental timeline. Participants attended three different experimental sessions (each separated at least by a week), two active HD-tACS sessions (20 Hz and 70 Hz), and one Sham (control) session. Sessions were counterbalanced across participants. Each session started with baseline EEG recording for 5 min at resting state followed by 50 trials of the handgrip task. After that, active or Sham HD-tACS stimulation was applied while performing another 50 trials of the handgrip task. Resting-state EEG and handgrip-task EEG were performed again 15 min and 45 min post-tACS/Sham.</p>
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<p>Computer screens showing the paradigm to the participant. During resting state, the participant looked at a black screen with a white cross in the center for 5 min. During the handgrip task, one trial consisted of reaching a threshold (red line inside the white bar), which was set to 15% of their maximum voluntary contraction, with a dynamometer using their right hand and staying on that threshold for 4 s. Each trial was followed by an inter-trial resting interval of 8 to 10 s. The stimulation electrodes that delivered HD-tACS were positioned on 5 recording electrodes over left M1 (anode: C3; cathodes: FC5, FC1, C3, CP5, and CP1).</p>
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<p>Effects of HD-tACS on average beta power at electrode C3 and CP3 normalized to baseline. Error bars represent standard error. Color indicates stimulation condition: orange = Sham, purple = 20 Hz, and pink = 70 Hz. (*** = <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Temporal evolution of MRBD on electrodes that showed significant changes (C3 and FC3) across the different NIBS (20 Hz HD-tACS, 70 Hz HD-tACS, and Sham). Time zero is motor task onset and Time 4 is motor task offset. Applying 20 Hz HD-tACS induced a more negative MRBD only after 15 min and 70 Hz HD-tACS induced a more positive MRBD after 15 min in both electrodes and after 45 min only on FC3. No changes were significant during Sham stimulation.</p>
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<p>Effects of HD-tACS on average MRBD percentage at electrode FC3 and C3 normalized to baseline. Error bars represent standard error. Color indicates stimulation condition: orange = Sham, purple = 20 Hz, and pink = 70 Hz. (* = <span class="html-italic">p</span> &lt; 0.05; *** = <span class="html-italic">p</span> &lt; 0.001)).</p>
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26 pages, 1026 KiB  
Review
Efficacy of Transcranial Direct Current Stimulation (tDCS) on Neuropsychiatric Symptoms in Multiple Sclerosis (MS)—A Review and Insight into Possible Mechanisms of Action
by James Chmiel and Marta Stępień-Słodkowska
J. Clin. Med. 2024, 13(24), 7793; https://doi.org/10.3390/jcm13247793 - 20 Dec 2024
Viewed by 534
Abstract
Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and [...] Read more.
Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal–midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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<p>Flowchart depicting the different phases of the systematic review.</p>
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<p>Flowchart describing potential mechanisms of action of tDCS in depressive and anxiety symptoms in MS.</p>
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15 pages, 915 KiB  
Review
Neurophysiologic Innovations in ALS: Enhancing Diagnosis, Monitoring, and Treatment Evaluation
by Ryan Donaghy and Erik P. Pioro
Brain Sci. 2024, 14(12), 1251; https://doi.org/10.3390/brainsci14121251 - 13 Dec 2024
Viewed by 479
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies. Full article
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<p>Relative percent drop of the motor unit number index (MUNIX) in a patient with ALS is greater and detected earlier than changes in the revised ALS functional rating scale (ALSFRS-R) score and slow vital capacity (SVC). (Modified and used with permission from reference [<a href="#B19-brainsci-14-01251" class="html-bibr">19</a>]).</p>
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<p>Transcranial magnetic stimulation excites a network of neurons in the underlying primary motor cortex (PMC) with a motor evoked potential (MEP) recorded over a contralateral intrinsic hand muscle (abductor pollicis brevis). (Modified and used with permission from reference [<a href="#B53-brainsci-14-01251" class="html-bibr">53</a>]).</p>
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18 pages, 1764 KiB  
Review
Audiological Features in Patients with Rheumatoid Arthritis: A Systematic Review
by Jiann-Jy Chen, Chih-Wei Hsu, Yen-Wen Chen, Tien-Yu Chen, Bing-Syuan Zeng and Ping-Tao Tseng
Int. J. Mol. Sci. 2024, 25(24), 13290; https://doi.org/10.3390/ijms252413290 - 11 Dec 2024
Viewed by 590
Abstract
Hearing impairment in patients with rheumatoid arthritis has been underestimated for decades. Rheumatoid arthritis can affect both the middle ear (specifically, the incudomalleolar and incudostapedial joints) and inner ear (including the cochlea and acoustic nerve) simultaneously. Despite ongoing research, consensus on effective treatments [...] Read more.
Hearing impairment in patients with rheumatoid arthritis has been underestimated for decades. Rheumatoid arthritis can affect both the middle ear (specifically, the incudomalleolar and incudostapedial joints) and inner ear (including the cochlea and acoustic nerve) simultaneously. Despite ongoing research, consensus on effective treatments for hearing impairment in these patients remains elusive. This systematic review aims to consolidate clinically relevant information for healthcare providers by summarizing current evidence on hearing impairment in rheumatoid arthritis patients. We conducted the current systematic review by searching platforms of PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect to retrieve eligible articles regarding hearing impairment related to rheumatoid arthritis. We extract any data on characteristics, pathophysiology, examination, and treatment related to rheumatoid arthritis. Based on the currently available evidence, we advocate for the use of specific audiometric tests to facilitate early detection of hearing impairment in these patients. Regular audiological assessments are recommended to monitor hearing ability and potentially prevent further deterioration. Finally, we propose a modified treatment protocol that integrates steroids, hydroxychloroquine, and non-invasive brain stimulation as a novel therapeutic approach for managing these symptoms. This protocol aims to offer clinicians new strategies to address hearing impairment in patients with rheumatoid arthritis effectively. Full article
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<p>PRISMA2020 Flowchart of current systematic review. <a href="#ijms-25-13290-f001" class="html-fig">Figure 1</a> illustrates the flowchart outlining the procedure of the present systematic review.</p>
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<p>Schematic diagram of the physiopathology of rheumatoid arthritis in audiology dysfunction. <a href="#ijms-25-13290-f002" class="html-fig">Figure 2</a>, which was drawn by the first author, illustrates the pathophysiology of rheumatoid arthritis-related antibodies and the formation of immune reactions contributing to audiological dysfunction. It overall consisted of six mechanisms, including (1) autoantibodies-induced vasculitis, (2) immune complex deposition in the labyrinthine artery, (3) degenerative changes in the organ of Corti, (4) direct neuritis, (5) incudomalleolar and incudostapedial joints stiffness, and (6) retro-cochlear auditory neuropathy.</p>
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<p>Flowchart of the multi-aspect treatment protocol for managing audiology dysfunction related to rheumatoid arthritis. <a href="#ijms-25-13290-f003" class="html-fig">Figure 3</a> presents a modified multi-aspect treatment protocol focusing on a 3-phase trial involving steroids, hydroxychloroquine, and non-invasive brain stimulation for managing audiological dysfunction related to rheumatoid arthritis. Note: This is a proposal of a future study protocol.</p>
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<p>A brief summary of the current systematic review. <a href="#ijms-25-13290-f004" class="html-fig">Figure 4</a> summarizes the key findings of the current systematic review.</p>
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22 pages, 3453 KiB  
Systematic Review
Noninvasive Brain Stimulation for Improving Cognitive Deficits and Clinical Symptoms in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis
by Yao Yin, Xueke Wang and Tingyong Feng
Brain Sci. 2024, 14(12), 1237; https://doi.org/10.3390/brainsci14121237 - 9 Dec 2024
Viewed by 578
Abstract
Objective: Noninvasive brain stimulation (NIBS) is a promising complementary treatment for attention-deficit/hyperactivity disorder (ADHD). However, its efficacy varies due to diverse participant profiles and methodologies. This meta-analysis, registered with PROSPERO (CRD42023457269), seeks to assess NIBS efficacy in improving cognitive deficits and clinical [...] Read more.
Objective: Noninvasive brain stimulation (NIBS) is a promising complementary treatment for attention-deficit/hyperactivity disorder (ADHD). However, its efficacy varies due to diverse participant profiles and methodologies. This meta-analysis, registered with PROSPERO (CRD42023457269), seeks to assess NIBS efficacy in improving cognitive deficits and clinical symptoms in individuals with ADHD. Methods: We systematically searched five databases (October 2024) for randomized controlled trials focusing on cognitive functions and clinical symptoms in individuals meeting the DSM/ICD criteria for ADHD. A meta-analytical synthesis was conducted using RevMan 5.4.1. Results: Meta-analyses found significant improvement in inhibitory control, working memory, and inattention in active transcranial direct current stimulation (tDCS) groups compared with sham groups. Conversely, repetitive transcranial magnetic stimulation (rTMS) did not demonstrate significant therapeutic benefits for ADHD symptoms. Additionally, four transcranial random noise stimulation (tRNS) and three transcranial alternating current stimulation (tACS) studies demonstrated promising improvements in executive functions and the alleviation of ADHD symptoms. Conclusions: The findings from this meta-analysis highlight NIBS as a promising adjunctive therapy for managing ADHD, advancing both theoretical knowledge and practical treatment options in this field. Full article
(This article belongs to the Special Issue Advances in ADHD—Second Edition)
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<p>PRISMA diagram of identifying eligible studies.</p>
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<p>The risk bias of tDCS studies [<a href="#B13-brainsci-14-01237" class="html-bibr">13</a>,<a href="#B14-brainsci-14-01237" class="html-bibr">14</a>,<a href="#B15-brainsci-14-01237" class="html-bibr">15</a>,<a href="#B16-brainsci-14-01237" class="html-bibr">16</a>,<a href="#B19-brainsci-14-01237" class="html-bibr">19</a>,<a href="#B24-brainsci-14-01237" class="html-bibr">24</a>,<a href="#B31-brainsci-14-01237" class="html-bibr">31</a>,<a href="#B32-brainsci-14-01237" class="html-bibr">32</a>,<a href="#B33-brainsci-14-01237" class="html-bibr">33</a>,<a href="#B34-brainsci-14-01237" class="html-bibr">34</a>,<a href="#B37-brainsci-14-01237" class="html-bibr">37</a>,<a href="#B38-brainsci-14-01237" class="html-bibr">38</a>,<a href="#B39-brainsci-14-01237" class="html-bibr">39</a>,<a href="#B41-brainsci-14-01237" class="html-bibr">41</a>,<a href="#B43-brainsci-14-01237" class="html-bibr">43</a>,<a href="#B44-brainsci-14-01237" class="html-bibr">44</a>].</p>
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<p>The risk bias of rTMS studies [<a href="#B17-brainsci-14-01237" class="html-bibr">17</a>,<a href="#B30-brainsci-14-01237" class="html-bibr">30</a>,<a href="#B40-brainsci-14-01237" class="html-bibr">40</a>].</p>
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<p>The risk bias of tACS and tRNS studies [<a href="#B18-brainsci-14-01237" class="html-bibr">18</a>,<a href="#B19-brainsci-14-01237" class="html-bibr">19</a>,<a href="#B45-brainsci-14-01237" class="html-bibr">45</a>,<a href="#B46-brainsci-14-01237" class="html-bibr">46</a>,<a href="#B48-brainsci-14-01237" class="html-bibr">48</a>,<a href="#B49-brainsci-14-01237" class="html-bibr">49</a>,<a href="#B50-brainsci-14-01237" class="html-bibr">50</a>].</p>
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<p>Meta−analysis of measures of (<b>A</b>) inhibitory control, (<b>B</b>) working memory, (<b>C</b>) cognitive flexibility, (<b>D</b>) inattention, and (<b>E</b>) hyperactivity/impulsivity in tDCS studies [<a href="#B13-brainsci-14-01237" class="html-bibr">13</a>,<a href="#B14-brainsci-14-01237" class="html-bibr">14</a>,<a href="#B15-brainsci-14-01237" class="html-bibr">15</a>,<a href="#B16-brainsci-14-01237" class="html-bibr">16</a>,<a href="#B19-brainsci-14-01237" class="html-bibr">19</a>,<a href="#B24-brainsci-14-01237" class="html-bibr">24</a>,<a href="#B31-brainsci-14-01237" class="html-bibr">31</a>,<a href="#B32-brainsci-14-01237" class="html-bibr">32</a>,<a href="#B33-brainsci-14-01237" class="html-bibr">33</a>,<a href="#B34-brainsci-14-01237" class="html-bibr">34</a>,<a href="#B37-brainsci-14-01237" class="html-bibr">37</a>,<a href="#B38-brainsci-14-01237" class="html-bibr">38</a>,<a href="#B39-brainsci-14-01237" class="html-bibr">39</a>,<a href="#B41-brainsci-14-01237" class="html-bibr">41</a>,<a href="#B43-brainsci-14-01237" class="html-bibr">43</a>,<a href="#B44-brainsci-14-01237" class="html-bibr">44</a>].</p>
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<p>Meta−analysis of measures of (<b>A</b>) inhibitory control, (<b>B</b>) working memory, (<b>C</b>) cognitive flexibility, (<b>D</b>) inattention, and (<b>E</b>) hyperactivity/impulsivity in tDCS studies [<a href="#B13-brainsci-14-01237" class="html-bibr">13</a>,<a href="#B14-brainsci-14-01237" class="html-bibr">14</a>,<a href="#B15-brainsci-14-01237" class="html-bibr">15</a>,<a href="#B16-brainsci-14-01237" class="html-bibr">16</a>,<a href="#B19-brainsci-14-01237" class="html-bibr">19</a>,<a href="#B24-brainsci-14-01237" class="html-bibr">24</a>,<a href="#B31-brainsci-14-01237" class="html-bibr">31</a>,<a href="#B32-brainsci-14-01237" class="html-bibr">32</a>,<a href="#B33-brainsci-14-01237" class="html-bibr">33</a>,<a href="#B34-brainsci-14-01237" class="html-bibr">34</a>,<a href="#B37-brainsci-14-01237" class="html-bibr">37</a>,<a href="#B38-brainsci-14-01237" class="html-bibr">38</a>,<a href="#B39-brainsci-14-01237" class="html-bibr">39</a>,<a href="#B41-brainsci-14-01237" class="html-bibr">41</a>,<a href="#B43-brainsci-14-01237" class="html-bibr">43</a>,<a href="#B44-brainsci-14-01237" class="html-bibr">44</a>].</p>
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<p>Meta-analysis of measures of core symptoms in rTMS studies [<a href="#B17-brainsci-14-01237" class="html-bibr">17</a>,<a href="#B30-brainsci-14-01237" class="html-bibr">30</a>,<a href="#B40-brainsci-14-01237" class="html-bibr">40</a>].</p>
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13 pages, 4259 KiB  
Review
Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) in Neurosurgery: Unexplored Path Towards Personalized Brain Surgery
by Martim Oliveira, Sofia Ribeiro, Asfand Baig Mirza, Amisha Vastani, Alba Díaz-Baamonde, Masumi Tanaka, Ali Elhag, Francesco Marchi, Prajwal Ghimire, Feras Fayez, Sabina Patel, Richard Gullan, Ranjeev Bhangoo, Keyoumars Ashkan, Francesco Vergani, Ana Mirallave-Pescador and José Pedro Lavrador
J. Pers. Med. 2024, 14(12), 1144; https://doi.org/10.3390/jpm14121144 - 9 Dec 2024
Viewed by 763
Abstract
Background: Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) is a non-operative technique that allows for magnetic cortical stimulation (TMS) and analysis of the electrical currents generated in the brain (EEG). Despite the regular utilization of both techniques independently, little is known about the potential impact of [...] Read more.
Background: Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) is a non-operative technique that allows for magnetic cortical stimulation (TMS) and analysis of the electrical currents generated in the brain (EEG). Despite the regular utilization of both techniques independently, little is known about the potential impact of their combination in neurosurgical practice. Methods: This scoping review, conducted following PRISMA guidelines, focused on TMS-EEG in epilepsy, neuro-oncology, and general neurosurgery. A literature search in Embase and Ovid MEDLINE returned 3596 records, which were screened based on predefined inclusion and exclusion criteria. After full-text review, three studies met the inclusion criteria. Two independent investigators conducted study selection and data extraction, with mediators resolving disagreements. The NHLBI tool was used to assess risk of bias in the included studies. Results: A total of 3596 articles were screened following the above-mentioned criteria: two articles and one abstract met the inclusion criteria. TMS-EEG is mentioned as a promising tool to evaluate tumor–brain interaction, improve preoperative speech mapping, and for lateralization epileptic focus in patients undergoing epilepsy surgery. Lack of detailed patient and outcome information preclude further considerations about TMS-EEG use beyond the potential applications of this technique. Conclusions: TMS-EEG research in neurosurgery is required to establish the role of this non-invasive brain stimulation-recording technique. Tumor–brain interaction, preoperative mapping, and seizure lateralization are in the front row for its future applications. Full article
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<p>Schematic workflow for TMS-EEG concept—created with BioRender.com.</p>
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<p>PRISMA flowchart.</p>
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<p>Brain–tumor interface, focus epilepticus detection, and speech mapping—created with BioRender.com.</p>
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<p>Number of papers returned at each step of search. Please note the * (asterisk) in a search is used as a truncation symbol to find variations of a word that share the same root.</p>
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58 pages, 2176 KiB  
Systematic Review
Advancing Neuropsychological Rehabilitation in Primary Progressive Aphasia Based on Principles of Cognitive Neuroscience: A Scoping Review and Systematic Analysis of the Data
by Evgenia Gkintoni and Emilia Michou
Brain Sci. 2024, 14(12), 1234; https://doi.org/10.3390/brainsci14121234 - 8 Dec 2024
Viewed by 618
Abstract
Background/Objectives: This systematic review of neuropsychological rehabilitation strategies for primary progressive aphasia will consider recent developments in cognitive neuroscience, especially neuroimaging techniques such as EEG and fMRI, to outline how these tools might be integrated into clinical practice to maximize treatment outcomes. Methods: [...] Read more.
Background/Objectives: This systematic review of neuropsychological rehabilitation strategies for primary progressive aphasia will consider recent developments in cognitive neuroscience, especially neuroimaging techniques such as EEG and fMRI, to outline how these tools might be integrated into clinical practice to maximize treatment outcomes. Methods: A systematic search of peer-reviewed literature from the last decade was performed following the PRISMA guidelines across multiple databases. A total of 63 studies were included, guided by predefined inclusion and exclusion criteria, with a focus on cognitive and language rehabilitation in PPA, interventions guided by neuroimaging, and mechanisms of neuroplasticity. Results: Integration of neuroimaging techniques contributes to the increase in the efficacy of interventions with critical information about the neural mechanisms underlying language deficits in the aphasias. Traditional rehabilitation strategies, technology-assisted interventions, and non-invasive brain stimulation techniques hold considerable promise for language improvement. Neuroimaging was also found to be necessary in subtype-specific differentiation toward tailoring therapeutic intervention. Evidence also shows that directed and sustained interventions using neuroplasticity can have long-term effects in managing the symptoms of PPA. Conclusions: The present review underlines the necessity of including cognitive neuroscience techniques within neuropsychological rehabilitation to enhance therapeutic outcomes in PPA. In addition, neuroimaging modalities such as EEG and fMRI are also of great importance in understanding the underlying neurobiology of language disturbances and guiding tailored interventions. Long-term benefits of these approaches should be evaluated, including their applicability in routine clinical practice. Full article
(This article belongs to the Section Behavioral Neuroscience)
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<p>Flowchart of PRISMA methodology.</p>
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<p>Heat map of brain regions affected by PPA variants.</p>
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<p>Trend line of intervention effectiveness in PPA rehabilitation.</p>
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<p>Venn diagram of PPA rehabilitation approaches.</p>
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17 pages, 4587 KiB  
Article
Improving Brain Metabolite Detection with a Combined Low-Rank Approximation and Denoising Diffusion Probabilistic Model Approach
by Yeong-Jae Jeon, Kyung Min Nam, Shin-Eui Park and Hyeon-Man Baek
Bioengineering 2024, 11(11), 1170; https://doi.org/10.3390/bioengineering11111170 - 20 Nov 2024
Viewed by 628
Abstract
In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive technique for monitoring brain metabolites. However, it is challenged by a low signal-to-noise ratio (SNR), often necessitating extended scan times to compensate. One of the conventional techniques for noise reduction is signal averaging, [...] Read more.
In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive technique for monitoring brain metabolites. However, it is challenged by a low signal-to-noise ratio (SNR), often necessitating extended scan times to compensate. One of the conventional techniques for noise reduction is signal averaging, which is inherently time-consuming and can lead to participant discomfort, thus posing limitations in clinical settings. This study aimed to develop a hybrid denoising strategy that integrates low-rank approximation and denoising diffusion probabilistic model (DDPM) to enhance MRS data quality and shorten scan times. Using publicly available 1H MRS datasets from 15 subjects, we applied the Casorati SVD and DDPM to obtain baseline and functional data during a pain stimulation task. This method significantly improved SNR, resulting in outcomes comparable to or better than averaging over 32 signals. It also provided the most consistent metabolite measurements and adequately tracked temporal changes in glutamate levels, correlating with pain intensity ratings after heating. These findings demonstrate that our approach enhances MRS data quality, offering a more efficient alternative to conventional methods and expanding the potential for the real-time monitoring of neurochemical changes. This contribution has the potential to advance MRS techniques by integrating advanced denoising methods to increase the acquisition speed and enhance the precision of brain metabolite analyses. Full article
(This article belongs to the Special Issue Monitoring and Analysis of Human Biosignals, 3rd Edition)
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<p>Overview of the CSVD and DDPM denoising process for functional MRS data. (<b>A</b>) The functional MRS data are displayed, illustrating the target spectrum with different signals from 1 to 320. (<b>B</b>) Casorati matrix <math display="inline"><semantics> <mrow> <mi>C</mi> </mrow> </semantics></math> is constructed using the functional MRS dataset and decomposed by the Casorati singular value decomposition (CSVD) into components <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>U</mi> </mrow> <mrow> <mi>r</mi> </mrow> </msub> <mrow> <msub> <mo stretchy="false">∑</mo> <mrow> <mi>r</mi> </mrow> </msub> <mrow> <msubsup> <mrow> <mi>V</mi> </mrow> <mrow> <mi>r</mi> </mrow> <mrow> <mo>*</mo> </mrow> </msubsup> </mrow> </mrow> </mrow> </semantics></math>. (<b>C</b>) Denoising diffusion probabilistic model (DDPM) is trained to the target data, illustrating the forward diffusion process from the initial state <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>s</mi> </mrow> <mrow> <mn>0</mn> </mrow> </msub> </mrow> </semantics></math> to noise <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>s</mi> </mrow> <mrow> <mi>T</mi> </mrow> </msub> </mrow> </semantics></math> and the reverse denoising process to recover the signal. NSA represents the number of signal averages; subscript t in DDPM indicates diffusion steps, while subscript <span class="html-italic">i</span> denotes the index for <span class="html-italic">i</span>-th non-averaged MRS data; and ns refers to the number of sample points.</p>
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<p>Comparison of methods for the baseline dataset (N = 15). Representative spectrum (1/32) in the baseline data for the following methods: NSA1 (no average, blue), NSA32 (average of 32 NSA1 scans, red), CSVD (denoising of NSA1 using CSVD, yellow), DDPM10 (denoising of NSA1 data using DDPM, violet), CSVD+DDPM2 (denoising of CSVD-denoised data using DDPM, green).</p>
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<p>SNR (<b>left</b>) and FWHM (<b>right</b>) values (mean <math display="inline"><semantics> <mrow> <mo>±</mo> </mrow> </semantics></math> standard deviation) using different approaches, calculated from 15 baseline MRS datasets. Asterisks at the top of the boxplot indicate statistical significance: * <span class="html-italic">p</span>-value &lt; 0.05, ** <span class="html-italic">p</span>-value &lt; 0.01, *** <span class="html-italic">p</span>-value &lt; 0.001. Methods include NSA1 (no signal average), DDPM10 (DDPM reverse denoising with 10 steps on NSA1 data), CSVD (Casorati singular value decomposition denoising on NSA1 data), NSA32 (32 signal averages), and CSVD+DDPM2 (DDPM reverse denoising with 2 steps on CSVD-denoised NSA1 data). SNR stands for signal-to-noise ratio, FWHM represents full width at half maximum. Significant differences were calculated using pairwise <span class="html-italic">t</span>-tests.</p>
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<p>Comparisons of CRLB values from the baseline MRS dataset (mean <math display="inline"><semantics> <mrow> <mo>±</mo> </mrow> </semantics></math> standard deviation) across different denoising methods. Asterisks above the boxplot indicate statistical significance levels: * <span class="html-italic">p</span>-value &lt; 0.05, ** <span class="html-italic">p</span>-value &lt; 0.01, *** <span class="html-italic">p</span>-value &lt; 0.001. Significant differences were assessed using pairwise <span class="html-italic">t</span>-tests. CRLB refers to the Cramer–Rao lower bound, which represents the standard error estimates returned by LCModel; lower CRLB values are associated with improved metabolite estimation.</p>
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<p>Comparisons of concentration values from the baseline MRS dataset (mean <math display="inline"><semantics> <mrow> <mo>±</mo> </mrow> </semantics></math> standard deviation) on different denoising methods. Asterisks at the top of the boxplot indicate statistical significance: * <span class="html-italic">p</span>-value &lt; 0.05. Significant differences were calculated using pairwise <span class="html-italic">t</span>-tests.</p>
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<p>Changes in metabolite concentrations from average values in the functional MRS dataset (N = 13). Panels show (<b>A</b>) Glu, (<b>B</b>) Glu/tCr, (<b>C</b>) tCr, (<b>D</b>) NAA, (<b>E</b>) NAA/tCr, (<b>F</b>) Glx, (<b>G</b>) Glx/tCr, (<b>H</b>) tCho, and (<b>I</b>) tCho/tCr. Blue lines represent NSA1, red lines indicate CSVD, yellow lines show DDPM10, and violet lines illustrate CSVD+DDPM2. Green lines denote NRS (pain intensity ratings). Yellow shaded region represents the baseline period with no stimulation (Time &lt; 0, duration = 3.12 min), while with capsaicin pain stimulation (Time &gt; 0, duration = 22.4 min), the blue shaded region indicates the heat-activated period (duration = 4.4 min).</p>
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<p>Changes in Glu concentrations from average values in the representative individual subjects. Panels show (<b>A</b>) subject #5, (<b>B</b>) subject #7, and (<b>C</b>) subject #8. Blue lines represent NSA1, red lines indicate CSVD, yellow lines show DDPM10, and violet lines illustrate CSVD+DDPM2. Green lines denote pain intensity rating (NRS) values.</p>
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15 pages, 1322 KiB  
Systematic Review
Audiovestibular Dysfunction Related to Anti-Phospholipid Syndrome: A Systematic Review
by Jiann-Jy Chen, Chih-Wei Hsu, Yen-Wen Chen, Tien-Yu Chen, Bing-Yan Zeng and Ping-Tao Tseng
Diagnostics 2024, 14(22), 2522; https://doi.org/10.3390/diagnostics14222522 - 11 Nov 2024
Cited by 1 | Viewed by 1324
Abstract
Background: Anti-phospholipid syndrome (APS) has emerged as a significant issue in autoimmune diseases over recent decades. Its hallmark feature is thromboembolic events, potentially affecting any vascularized area including the microcirculation of the inner ear. Since the first case report of APS-related audiovestibular dysfunction [...] Read more.
Background: Anti-phospholipid syndrome (APS) has emerged as a significant issue in autoimmune diseases over recent decades. Its hallmark feature is thromboembolic events, potentially affecting any vascularized area including the microcirculation of the inner ear. Since the first case report of APS-related audiovestibular dysfunction described in 1993, numerous reports have explored the association between APS-related antibodies and audiovestibular dysfunction. These studies indicate a higher prevalence of APS-related antibodies in patients with sensorineural hearing loss compared to healthy controls. Unlike other idiopathic hearing loss disorders, audiovestibular dysfunction associated with APS may respond to appropriate treatments, highlighting the importance of timely recognition by clinicians to potentially achieve favorable outcomes. Therefore, this systematic review aims to consolidate current evidence on the characteristics, pathophysiology, assessment, and management of audiovestibular dysfunction linked to APS. Methods: This systematic review utilized electronic searches of the PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect online platforms. The initial search was performed on 27 January 2024, with the final update search completed on 20 June 2024. Results: Based on theoretical pathophysiology, anticoagulation emerges as a pivotal treatment strategy. Additionally, drawing from our preliminary data, we propose a modified protocol combining anticoagulants, steroids, and non-invasive brain stimulation to offer clinicians a novel therapeutic approach for managing these symptoms. Conclusions: Clinicians are encouraged to remain vigilant about the possibility of APS and its complex audiovestibular manifestations, as prompt intervention could stabilize audiovestibular function effectively. Full article
(This article belongs to the Special Issue Etiology, Diagnosis, and Treatment of Congenital Hearing Loss)
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<p>Flowchart of the whole systematic review procedure.</p>
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<p>Schematic diagram of the physiopathology of anti-phospholipid syndrome in audiovestibular dysfunction.</p>
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<p>Flowchart of the modified anticoagulants plus steroid and non-invasive brain stimulation treatment protocol to manage anti-phospholipid syndrome-related audiovestibular dysfunction. Note: this is a proposal of a future study protocol.</p>
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23 pages, 5435 KiB  
Review
Transcranial Focused Ultrasound Neuromodulation in Psychiatry: Main Characteristics, Current Evidence, and Future Directions
by Ahmadreza Keihani, Claudio Sanguineti, Omeed Chaichian, Chloe A. Huston, Caitlin Moore, Cynthia Cheng, Sabine A. Janssen, Francesco L. Donati, Ahmad Mayeli, Khaled Moussawi, Mary L. Phillips and Fabio Ferrarelli
Brain Sci. 2024, 14(11), 1095; https://doi.org/10.3390/brainsci14111095 - 30 Oct 2024
Viewed by 2036
Abstract
Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely [...] Read more.
Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely and non-invasively stimulate deep brain structures with millimetric precision, offering distinct advantages in terms of accessibility to non-cortical regions over other NIBS methods. However, to date, several tFUS aspects still need to be characterized; furthermore, there are only a handful of studies that have utilized tFUS in psychiatric populations. This narrative review provides an up-to-date overview of key aspects of this NIBS technique, including the main components of a tFUS system, the neuronavigational tools used to precisely target deep brain regions, the simulations utilized to optimize the stimulation parameters and delivery of tFUS, and the experimental protocols employed to evaluate the efficacy of tFUS in psychiatric disorders. The main findings from studies in psychiatric populations are presented and discussed, and future directions are highlighted. Full article
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<p><b>Overview of key components of the tFUS setup.</b> (Left panel): The top left panel displays the main components of the tFUS setup, including the tFUS parameter space control unit and its transducer (image adapted from the BrainBox manufacturer, Cardiff, UK). The lower left panel shows the neuronavigation system, featuring infrared cameras for subject tracking and transducer positioning to assist in targeting during stimulation (image adapted from the NEUROLITH-TPS manufacturer, Tägerwilen, Switzerland). (Right panel): An example of real-time neuronavigation while tracking the subject and transducer with an infrared camera (images created using Brainsight software V2.5.3, Montréal, Canada). The top right panel shows scalp points (in green) that are taken for coregistering the brain MRI with the subject’s head position in real time. The bottom right panel displays the target and transducer positions, which are utilized to ensure an accurate and optimized stimulation.</p>
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<p><b>Illustration of the geometry and parameters of the tFUS transducer.</b> Aperture diameter (D), curvature radius (R), fundamental frequency (FF), sonication duration (SD), acoustic pressure (P(t)), pulse duration (PD), interstimulus interval (ISI), and pulse repetition frequency (PRF) are displayed. These parameters define the sonication protocol.</p>
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<p><b>Depiction of the acoustic simulation estimated for tFUS targeting of a brain region.</b> The simulation, which relies on individual neuroimaging data, determines the trajectory and target depth based on MNI or native space coordinates. The transducer position, acoustic focus, and predicted sonication protocol are simulated to assess both acoustic and thermal effects on the targeted brain region (image created with k-plan software (<a href="https://brainbox-neuro.com/products/k-plan" target="_blank">https://brainbox-neuro.com/products/k-plan</a>) from BrainBox).</p>
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<p><b>Sham strategies and evaluation methods used in tFUS studies.</b> (Left panel): The illustration presents the subject enrollment and blinding process, in which participants are randomized into either active (tFUS ON) or sham (tFUS OFF) conditions. The choice of gel-pad type can further enhance blinding by minimizing differences in scalp perception between active and sham sessions (the 3D visualization of the transducer on the head model was adapted from [<a href="#B62-brainsci-14-01095" class="html-bibr">62</a>]). (Right panel): Different experimental approaches for evaluating the effects of tFUS on brain function. These include offline methods, such as pre- and post-tFUS resting-state fMRI (rs-fMRI) or hd-EEG (EEG electrode cap image adapted from Compumedics Neuroscan company, Victoria, Australia), and online methods using concurrent tFUS with either rs-fMRI or hd-EEG to capture immediate neurophysiological changes induced by the stimulation.</p>
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