Search Results (735)

Background/Objectives: There is a bidirectional relationship between major depressive disorder (MDD) and type 2 diabetes (T2D), as MDD increases the risk of T2D by 38% to 67%, and T2D increases the risk of MDD by 15% to 33%. Many factors contribute to the occurrence of comorbid MDD and T2D, including converging pathophysiological pathways like inflammation. The objective of this review was to comprehensively summarize available evidence on the relationship between MDD, T2D, and inflammation. Results: Although the precise mechanisms linking T2D and MDD are still not fully understood, shared inflammatory mechanisms likely contributes to the heightened risk of developing this comorbidity. To date, the evidence supports that chronic low-grade inflammation is a feature of both MDD and T2D and has been shown to interact with pathways that are relevant to the development of both chronic disorders, including the hypothalamic–pituitary–adrenal (HPA) axis, neuroplastic processes, gut microbiome, insulin resistance, and adipose tissue dysfunction. Through their impact on inflammation, dietary and physical activity interventions can play a role in the risk and management of MDD and T2D. Conclusions: Deepening our understanding of the mechanisms underlying the augmented inflammatory responses observed in individuals with the MDD and T2D comorbidity is essential for tailoring appropriate therapeutic strategies. Full article

Major depressive disorder (MDD) is a debilitating mental illness, and it is considered to be one of the leading causes of disability globally. The etiology of MDD is multifactorial, involving an interplay between biological, psychological, and social factors. Early life represents a critical period for development. Exposure to adverse childhood experiences is a major contributor to the global burden of disease and disability, doubling the risk of developing MDD later in life. Evidence suggests that stressful events experienced during that timeframe play a major role in the emergence of MDD, leading to epigenetic modifications, which might, in turn, influence brain structure, function, and behavior. Neuroplasticity seems to be a primary pathogenetic mechanism of MDD, and, similarly to epigenetic mechanisms, it is particularly sensitive to stress in the early postnatal period. In this review, we will collect and discuss recent studies supporting the role of epigenetics and neuroplasticity in the pathogenesis of MDD, with a focus on early life stress (ELS). We believe that understanding the epigenetic mechanisms by which ELS affects neuroplasticity offers potential pathways for identifying novel therapeutic targets for MDD, ultimately aiming to improve treatment outcomes for this debilitating disorder. Full article

Studies about the effects of SARS-CoV-2 on pregnant women and children born to positive women are controversial with regard to possible inner ear-related damage but most of them do not detect the involvement of this virus in auditory function. However, only a few studies on long-term effects on language development are currently available because of the recent onset of the pandemic. The aim of this study was to investigate the impact of SARS-CoV-2 infection on perceptual and expressive abilities and the emerging development of communication in young children. To this purpose, the MacArthur–Bates Communicative Development Inventory—Words and Gestures form (CDI-WG), was administered to parents. In total, 115 children whose mother was infected by SARS-CoV-2 during pregnancy were enrolled in the study and evaluated at the Audiology Service of the Modena University Hospital. All children underwent Otoacoustic Emissions (OAE) at birth: 114/115 had a “pass” result bilaterally, while 1 case had a unilateral “refer” result. Overall, 110/115 newborns (95.65%) underwent audiological evaluation between 10–18 months of age. In 5/110 patients (3.6%), the Pure Tone Average (PTA) result was equal to 35 dB; one case had a hearing threshold of around 50 dB due to a bilateral effusive otitis media. A notable finding was the percentage of children with tubal dysfunction in both evaluations, within 2 months of age and around 12 months of age. Most children revealed normal hearing. The CDI-WG was completed by 56/115 families. The rate of children below the fifth percentile was 8.9% for sentences understood, 12.5% for words understood, and 5.4% for words produced. Concerning CDI-Gestures, only 2 children (3.6%) were below the fifth percentile. A structured audiological follow-up in association with the evaluation of communication skills of children appears fundamental, particularly in the years of maximum neuroplasticity. Long-term studies are still necessary to evaluate the possible consequences of the pandemic. Full article

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor because it does not bind to a known specific receptor on the plasma membrane and functions primarily as an unfolded protein response (UPR) regulator in the endoplasmic reticulum. Data on the effects of CDNF on nonmotor behavior and monoamine metabolism are limited. Here, we performed the intracerebroventricular injection of a recombinant CDNF protein at doses of 3, 10, and 30 μg in C57BL/6 mice. No adverse effects of the CDNF injection on feed and water consumption or locomotor activity were observed for 3 days afterwards. Decreases in body weight and sleep duration were transient. CDNF-treated animals demonstrated improved performance on the operant learning task and a substantial decrease in anxiety and behavioral despair. CDNF in all the doses enhanced serotonin (5-HT) turnover in the murine frontal cortex, hippocampus, and midbrain. This alteration was accompanied by changes in the mRNA levels of the 5-HT1A and 5-HT7 receptors and in monoamine oxidase A mRNA and protein levels. We found that CDNF dramatically increased c-Fos mRNA levels in all investigated brain areas but elevated the phosphorylated-c-Fos level only in the midbrain. Similarly, enhanced CREB phosphorylation was found in the midbrain in experimental animals. Additionally, the upregulation of a spliced transcript of XBP1 (UPR regulator) was detected in the midbrain and frontal cortex. Thus, we can hypothesize that exogenous CDNF modulates the UPR pathway and overall neuronal activation and enhances 5-HT turnover, thereby affecting learning and emotion-related behavior. Full article

As our population ages, the medical challenges it faces become increasingly acute, with chronic kidney disease (CKD) becoming more prevalent among older adults. Frailty is alarmingly more common in CKD patients than in the general populace, putting the elderly at high risk of both physical and cognitive decline. CKD not only accelerates physical deterioration, but also heightens vascular dysfunction, calcification, arterial rigidity, systemic inflammation, oxidative stress, and cognitive impairment. Cognitive frailty, a distinct syndrome marked by cognitive deficits caused by physiological causes (excluding Alzheimer’s and other dementias), is a critical concern. Although cognitive impairment has been well-studied, the molecular mechanisms driving cognitive frailty remain largely uncharted. Comprehensive interventions, including cutting-edge pharmaceuticals and lifestyle changes, are pivotal and effective, especially in the early stages of CKD. Recent research suggests that systematic exercise could counteract cognitive decline by improving brain blood flow, boosting neuroplasticity through the brain-derived neurotrophic factor (BDNF), and by triggering the release of neurotrophic factors such as insulin-like growth factor (IGF-1). This review delves into the molecular pathways of cognitive frailty in CKD, identifies key risk factors, and highlights therapeutic approaches, particularly the potent role of exercise in enhancing cognitive health. Full article

Background/Objectives: Functional MRI (fMRI) is widely used to assess language lateralization, but its application in patients with brain tumors can be hindered by cognitive impairments, compensatory neuroplasticity, and artifacts due to patient movement or severe aphasia. Gray matter volume (GMV) analysis via voxel-based morphometry (VBM) in language-related brain regions may offer a stable complementary approach. This study investigates the relationship between GMV and fMRI-derived language lateralization in healthy individuals and patients with left-hemisphere brain tumors, aiming to enhance accuracy in complex cases. Methods: The MRI data from 22 healthy participants and 28 individuals with left-hemisphere brain tumors were analyzed. Structural T1-weighted and functional images were obtained during three language tasks. Language lateralization was assessed based on activation in predefined regions of interest (ROIs), categorized as typical (left) or atypical (right or bilateral). The GMV in these ROIs was measured using VBM. Linear regressions explored GMV-lateralization associations, and logistic regressions predicted the lateralization based on the GMV. Results: In the healthy participants, typical left-hemispheric language dominance correlated with higher GMV in the left pars opercularis of the inferior frontal gyrus. The brain tumor participants with atypical lateralization showed increased GMV in six right-hemisphere ROIs. The GMV in the language ROIs predicted the fMRI language lateralization, with AUCs from 80.1% to 94.2% in the healthy participants and 78.3% to 92.6% in the tumor patients. Conclusions: GMV analysis in language-related ROIs effectively complements fMRI for assessing language dominance, particularly when fMRI is challenging. It correlates with language lateralization in both healthy individuals and brain tumor patients, highlighting its potential in preoperative language mapping. Further research with larger samples is needed to refine its clinical utility. Full article

Background/Objectives: Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and impaired motor performance. This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) during virtual reality (VR) tasks on the motor performance of women with FM. Methods: Participants were divided into two groups: Group A received active tDCS for 10 days followed by sham tDCS for 10 days, while Group B received the opposite sequence. Both groups performed VR tasks using MoveHero software (v. 2.4) during the tDCS sessions. Motor performance was assessed by the number of hits (movement with correct timing to reach the targets) and absolute (accuracy measure) and variable (precision measure) errors during VR tasks. Participants were 21 women, aged 30–50 years, and diagnosed with FM. Results: Group A, which received active tDCS first, presented significant improvements in motor performance (number of hits and absolute and variable errors). The benefits of active tDCS persisted into the sham phase, suggesting a lasting neuroplastic effect. Conclusions: tDCS during VR tasks significantly improved motor performance in women with FM, particularly in complex, extensive movements. These findings indicate that tDCS enhances neuroplasticity, leading to sustained motor improvements, making it a promising therapeutic tool in FM rehabilitation. Full article

Introduction: The spinal rehabilitation process plays a crucial role in SCI patients’ lives, and recent developments in VR have the potential to efficiently engage SCI patients in therapeutic activities and promote neuroplasticity. Objective: The primary objective of this study is to assess a complete review of the extended impacts of VR-assisted training on spine rehabilitation in SCI patients. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a single database search in PubMed/Medline between the dates 1 January 2010 and 1 February 2024. MESH terms and keywords were combined in the following search strategy: (Augmented Reality OR VR OR Virtual Reality) AND (Spine OR Spinal) AND Rehabilitation. Included articles were written in English, involved adults with SCI, included an intervention with VR, AR, or any mixed reality system, and assessed changes in outcomes after the intervention. Results: The search produced 257 articles, and 46 of them were allocated for data extraction to evaluate 652 patients. Both when VR training was analyzed and reviewed separately, and when compared to traditional training, the findings exhibited predominantly promising outcomes, reflecting a favorable trend in the study. VR technologies were used in different settings and customizations, and the medium total time of VR training among the studies was 60.46 h per patient. Conclusions: This auspicious outcome of the study further motivates the intervention of VR and AR in the rehabilitation of SCI patients along with ameliorating their overall holistic well-being. Full article

Introduction: Bulimia nervosa (BN) is a disorder primarily affecting adolescent females, characterized by episodes of binge eating followed by inappropriate compensatory behaviors aimed at preventing weight gain, including self-induced vomiting and the misuse of diuretics, laxatives, and insulin. The precise etiology of BN remains unknown, with factors such as genetics, biological influences, emotional disturbances, societal pressures, and other challenges contributing to its prevalence. First-line treatment typically includes pharmacotherapy, which has shown moderate effectiveness. Neuroimaging evidence suggests that altered brain activity may contribute to the development of BN, making interventions that directly target the brain extremely valuable. One such intervention is repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique that has been garnering interest in the medical community for many years. Methods: This review explores the use of rTMS in the treatment of BN. Searches were conducted in the PubMed/Medline, ResearchGate, and Cochrane databases. Results: Twelve relevant studies were identified. Analysis of the results from these studies reveals promising findings, particularly regarding key parameters in the pathophysiology of BN. Several studies assessed the impact of rTMS on binge episodes. While some studies did not find significant reductions, most reported decreases in binge eating and purging behaviors, with some cases showing complete remission. Reductions in symptoms of depression and food cravings were also demonstrated. However, results regarding cognitive improvement were mixed. The discussion focused heavily on potential mechanisms of action, including neuromodulation of brain networks, induction of neuroplasticity, impact on serotonergic dysfunction, anti-inflammatory action, and HPA axis modulation. rTMS was found to be a safe intervention with no serious side effects. Conclusions: rTMS in the treatment of BN appears to be a promising intervention that alleviates some symptoms characteristic of the pathophysiology of this disorder. An additional effect is a significant reduction in depressive symptoms. However, despite these findings, further research is required to confirm its effectiveness and elucidate the mechanisms of action. It is also recommended to further investigate the potential mechanisms of action described in this review. Full article

Background: Phantom limb pain (PLP) is highly prevalent after amputation. However, the influence of non-painful sensations (PLS) remains unclear. This study examines the PLP-PLS index as a novel tool to differentiate PLP from PLS and explores the association of clinical factors with the index. Methods: We conducted a cross-sectional analysis of baseline data from 112 participants in a previous factorial trial in patients with unilateral traumatic lower limb amputation. Linear regression models were used to examine the associations between the index and various demographic, psychological and clinical factors. Logistic and Poisson regression, and e-value calculation were utilized for sensitivity analyses. Results: Adjusted multivariable linear regression models demonstrated significant associations of phantom movement sensation (β: −1.532; 95% CI: −2.615 to −0.449; p = 0.006) and time since amputation (β: 0.005; 95% CI: 0.0006 to 0.0101; p = 0.026) with the PLP-PLS index. These findings were confirmed by multivariable logistic regression (phantom movement sensation OR: 0.469; 95% CI: 0.200 to 1.099, p = 0.082; time since amputation OR: 1.003; 95% CI: 1.00003 to 1.007; p = 0.048) and sensitivity analyses. Conclusions: Time since amputation and phantom movement sensation likely reflect distinct phenotypes and potential mechanisms for PLP and PLS. The PLP-PLS index is a promising clinical tool for selecting therapies to prevent/treat PLP and for measuring treatment effects to modulate phantom pain. These findings emphasize the importance of understanding the mechanisms underlying PLP and PLS for improving clinical management and guiding future research. Full article

This study explores neuroplasticity through the use of virtual reality (VR) and brain–computer interfaces (BCIs). Neuroplasticity is the brain’s ability to reorganize itself by forming new neural connections in response to learning, experience, and injury. VR offers a controlled environment to manipulate sensory inputs, while BCIs facilitate real-time monitoring and modulation of neural activity. By combining VR and BCI, researchers can stimulate specific brain regions, trigger neurochemical changes, and influence cognitive functions such as memory, perception, and motor skills. Key findings indicate that VR and BCI interventions are promising for rehabilitation therapies, treatment of phobias and anxiety disorders, and cognitive enhancement. Personalized VR experiences, adapted based on BCI feedback, enhance the efficacy of these interventions. This study underscores the potential for integrating VR and BCI technologies to understand and harness neuroplasticity for cognitive and therapeutic applications. The researchers utilized the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) method to conduct a comprehensive and systematic review of the existing literature on neuroplasticity, VR, and BCI. This involved identifying relevant studies through database searches, screening for eligibility, and assessing the quality of the included studies. Data extraction focused on the effects of VR and BCI on neuroplasticity and cognitive functions. The PRISMA method ensured a rigorous and transparent approach to synthesizing evidence, allowing the researchers to draw robust conclusions about the potential of VR and BCI technologies in promoting neuroplasticity and cognitive enhancement. Full article

Ketone bodies are considered alternative fuels for the brain when glucose availability is limited. To determine the neuroregenerative potential of D,L-sodium-beta-hydroxybutyrate (D/L-BHB), Sprague Dawley rat primary cortical neurons were exposed to simulated central nervous system injury using a scratch assay. The neuronal cell migration, cell density and degree of regeneration in the damaged areas (gaps) in the absence (control) and presence of BHB (2 mM) were documented with automated live-cell imaging by the CytoSMART system over 24 h, which was followed by immunocytochemistry, labeling synapsin-I and β3-tubulin. The cell density was significantly higher in the gaps with BHB treatment after 24 h compared to the control. In the control, only 1.5% of the measured gap areas became narrower over 24 h, while in the BHB-treated samples 49.23% of the measured gap areas became narrower over 24 h. In the control, the gap expanded by 63.81% post-injury, while the gap size decreased by 10.83% in response to BHB treatment, compared to the baseline. The cell density increased by 97.27% and the gap size was reduced by 74.64% in response to BHB, compared to the control. The distance travelled and velocity of migrating cells were significantly higher with BHB treatment, while more synapsin-I and β3-tubulin were found in the BHB-treated samples after 24 h, compared to the control. The results demonstrate that D/L-BHB enhanced neuronal migration and molecular processes associated with neural regeneration and axonogenesis. These results may have clinical therapeutic applications in the future for nervous system injuries, such as for stroke, concussion and TBI patients. Full article

Background. Incidentally discovered low-grade gliomas (iLGGs) are very rare and little is still known about their associated functional imaging activation patterns, white-matter status, and plasticity potential. Recent studies shed light on several clinical factors responsible for the good clinical status observed in these patients versus those with their symptomatic counterpart (sLGGs), including small volume. Comparisons were typically carried out by comparing iLGGs with the wider and more heterogeneous sLGG group. In this study, we investigated whether iLGGs affect the brain differently from comparably small sLGGs. Method. Starting from a sample of 13 patients with iLGG, in the current comparative cross-sectional study, we identified a group of patients with sLGGs, primarily matched by lesion volume. We looked for potential differences between the two groups in language-related functional and structural parameters (the fMRI network associated with naming and white-matter fascicles). Results. The t-test did not show significant differences in the fMRI network, but these emerged when performing masking. No significant differences were observed at the white-matter level. Conclusions. Given that small volumes characterized both groups and that demographic variables were comparable, too, we hypothesized that differences between the two groups could be attributed to alternative lesion-related parameters. We discussed these findings from clinical and neurosurgical perspectives. Full article

As the global prevalence of motor disabilities continues to rise, there is a pressing need for advanced solutions in physical rehabilitation. This systematic review examines the progress and challenges of implementing robotic technologies in the motor rehabilitation of patients with physical disabilities. The integration of robotic technologies such as exoskeletons, assistive training devices, and brain–computer interface systems holds significant promise for enhancing functional recovery and patient autonomy. The review synthesizes findings from the most important studies, focusing on the clinical effectiveness of robotic interventions in comparison to traditional rehabilitation methods. The analysis reveals that robotic therapies can significantly improve motor function, strength, co-ordination, and dexterity. Robotic systems also support neuroplasticity, enabling patients to relearn lost motor skills through precise, controlled, and repetitive exercises. However, the adoption of these technologies is hindered by high costs, the need for specialized training, and limited accessibility. Key insights from the review highlight the necessity of personalizing robotic therapies to meet individual patient needs, alongside addressing technical, economic, social, and cultural barriers. The review also underscores the importance of continued research to optimize these technologies and develop effective implementation strategies. By overcoming these challenges, robotic technologies can revolutionize motor rehabilitation, improving quality of life and social integration for individuals with motor disabilities. Full article

Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion–symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia. Full article