The maintenance of complex visual scenes in working memory may require activation of working memory manipulation circuits in the dlPFC: a preliminary report.

Past research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing,1,2,3 in addition to working memory4, 5. Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, we designed a task that looked at working memory performance during fMRI under both emotional and non-emotional conditions, and tested it in this preliminary report. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth6. Results showed a significant main effect of the 'sort' condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. Although preliminary, these results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these initial results show that the dlPFC is implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks.

Imaging Guidelines during Percutaneous Liver Ablation to Optimize Outcomes and Patient Safety.

Image-guided ablation procedures have become a mainstay in cancer therapy. Typically performed from a percutaneous approach, thermal-based ablation procedures rely heavily on imaging guidance both prior to and during the procedure itself. Advances in imaging as they relate to ablation procedures are as important to successful treatments as advancements in the ablation technology itself. Imaging as it relates to procedural planning, targeting and monitoring, and assessment of procedural endpoint is the focus of this article.

Rare Congenital Upper Lip Pit.

Congenital lip pits are characterized by sinuses or fistulas in the lips that can occur in isolation or as part of a genetic disorder. A 6-year-old girl with a right upper lip lesion present at birth presented with recurrent swelling and occasional erythema. Examination revealed a mildly swollen punctum at the right upper wet/dry vermillion with expressible serous drainage. There were no other phenotypic or cognitive concerns. The lesion was surgically excised using vertical wedge resection. The postoperative course showed well well-healed incision. The pathology report confirmed a lip pit. The family was referred to genetics for further evaluation. Van der Woude syndrome (VWS) is a genetic disorder associated with abnormal development of the paramedian lip. Most congenital lip pits are primarily found on the lower lips, with paramedian lip pits being the most common. Upper lateral lip pits with or without accompanying lip pits are considerably rarer. Though VWS is commonly associated with mutations in the interferon regulatory factor 6 or grainyhead-like protein 3 genes, ~25% of affected individuals lack an identified genetic etiology. A high index of suspicion for VWS is warranted if lip pits are present in the absence of other phenotypic abnormalities and should prompt genetic testing for interferon regulatory factor 6 and grainyhead-like protein 3 mutations. Multidisciplinary teams should consider patient self-esteem, quality of life, and potential family planning when deciding on surgical intervention for lip pits. Surgical management of pits should entail tissue-preserving techniques such as vertical wedge resection and inverted T-lip reduction to prevent whistle-lip deformity.

Eligibility for antiamyloid treatment: preparing for disease-modifying therapies for Alzheimer's disease.

BACKGROUND: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) have early evidence of efficacy. Widespread delivery of DMTs will require major service reconfiguration. Treatment pathways will need to include triaging for eligibility, regular infusions and baseline and follow-up MRI scanning. A critical step in planning is provision of real-world estimates of patients likely to be eligible for triaging, but these are challenging to obtain. METHODS: We performed a retrospective service evaluation of patients attending five memory services across North and East London and a national specialist cognitive disorders service. We examined the likely proportion of patients who would (1) be referred for triaging for DMTs and (2) potentially be suitable for treatments. RESULTS: Data from a total of 1017 patients were included, 517 of whom were seen in community memory services and 500 in a specialist clinic. In the memory services, 367/517 (71%) were diagnosed with possible AD. After exclusions of those in whom cognitive and frailty scores, MRI contraindications or anticoagulant use indicated they would be unlikely to be suitable, an estimated 32% would be eligible for triaging. In the specialist cognitive clinic, where additional investigations are available, 14% of those seen (70/500) would be potentially eligible for treatment. CONCLUSIONS: While a sizeable proportion of patients attending memory clinics may be referred for triaging for DMTs for AD, only a minority are likely to be suitable for these, as demonstrated in patients seen in specialist cognitive services. This will need to be considered when designing pathways for DMT delivery.

Intermittent theta-burst stimulation to the right dorsolateral prefrontal cortex may increase potentiated startle in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.

Threat of shock increases distractor susceptibility during the short-term maintenance of visual information.

Elevated arousal in anxiety is thought to affect attention control. To test this, we designed a visual short-term memory (VSTM) task to examine distractor suppression during periods of threat and no-threat. We hypothesized that threat would impair performance when subjects had to filter out large numbers of distractors. The VSTM task required subjects to attend to one array of squares while ignoring a separate array. The number of target and distractor squares varied systematically, with high (four squares) and low (two squares) target and distractor conditions. This study comprised two separate experiments. Experiment 1 used startle responses and white noise as to directly measure threat-induced anxiety. Experiment 2 used BOLD to measure brain responses. For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. For Experiment 2, we found that accuracy was affected by threat, such that the distractor load negatively impacted accuracy only in the threat condition. We also found threat-related differences in parietal cortex activity. Overall, these findings suggest that threat affects distractor susceptibility, impairing filtering of distracting information. This effect is possibly mediated by hyperarousal of parietal cortex during threat.

A Single-Center Experience with a Shear-Thinning Conformable Embolic.

The purpose of this study was to evaluate the technical success, effectiveness, and safety of transarterial embolization for acute bleeding management with a shear-thinning conformable embolic. This single-center retrospective study evaluated outcomes after embolization using Obsidio conformable embolic (OCE). Technical success was defined as performing transarterial embolization within the target vessel to complete stasis of antegrade flow. Treatment effectiveness was defined as cessation of bleeding for patients. Eleven patients underwent 11 embolization procedures. A total of 16 arteries were embolized. Indications for embolization were spontaneous tumor bleeding (6/11), hematuria (2/11), active duodenal bleeding (1/11), portal hypertensive bleeding (1/11), and rectus sheath hematoma (1/11). The technical success rate was 100%. The median vessel diameter was 2 mm (range, 1-3 mm). There were no adverse events or off-target embolization. OCE demonstrated technical success and treatment effectiveness with a short-term safety profile for transarterial embolization interventions.

Follmann Balanitis: An Unusual Case of Syphilis.

A 33-year-old man presented with suprapubic abdominal pain and small vesicular lesions on the foreskin of the penis. Based on the presentation, he was empirically treated for genital herpes, although the herpes simplex virus swab was negative. He returned to the emergency department 4 months after his initial presentation with worsening symptoms that were consistent with balanoposthitis and cystitis. He was tachycardic and febrile on presentation. He denied any sexual contact for the last 3 months, with previous negative screening tests for sexually transmitted infections. Syphilis was eventually diagnosed during this admission. The incidence rates of syphilis have increased in recent years, and the infection is often undiagnosed given atypical manifestations. Here we present an atypical manifestation of syphilis that was initially misdiagnosed as herpes simplex virus.

Neuromodulation's Role in Functional Restoration in Paraplegic and Quadriplegic Patients.

Neuromodulation is an alternative, minimally invasive treatment option that, at times, is used as a last resort for chronic pain conditions that are often refractory to other treatment modalities. Moreover, it offers promising prospects for individuals grappling with the formidable challenges posed by paraplegia and quadriplegia resulting from spinal cord injuries. This review article provides a comprehensive assessment of current treatment modalities specifically tailored for paraplegic and quadriplegic patients. We aim to evaluate the existing surgical and non-surgical interventions while delving into the role of neuromodulation in the restoration of function for individuals afflicted with these debilitating conditions. Additionally, we review the efficacy, limitations, and comparative outcomes of diverse treatment strategies available for the management of paraplegia and quadriplegia. Emphasizing the critical need for effective interventions beyond the initial 24 h surgical window, we elucidate the challenges associated with conventional therapies and their limited success in achieving comprehensive functional restoration. Central to this review is an in-depth exploration of neuromodulation's transformative potential in ameliorating the deficits caused by spinal cord injuries. With a particular focus on spinal cord stimulation (SCS), we analyze and compare the outcomes of neuromodulation modalities and traditional treatment regimens, shedding light on the promising strides made in fostering sensory perception, motor function, and patient satisfaction.

Mechanical Venous Thrombectomy for Deep Venous Thrombosis in Cancer Patients: A Single-Center Retrospective Study.

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.

Bimekizumab for the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin condition characterized by Th17 T cell-mediated inflammation. An emerging treatment option for psoriasis is bimekizumab, a humanized monoclonal antibody targeting cytokines IL-17A and IL-17F. Phase I trials evaluating bimekizumab reported strong safety, tolerability, and clinical efficacy with most common treatment emergent adverse events being mild to moderate in nature. Phase II trials evaluated dosing intervals, revealing that higher dosages or more frequent administration of bimekizumab resulted in minimal increases in adverse events. Phase III trials and open label extension studies demonstrated a rapid, sustained clinical response when compared with placebo and active comparators. Bimekizumab shows strong efficacy in the treatment of psoriasis and has potential in the treatment of other Th17-mediated pathologies.

Psoriasis is a chronic skin problem caused by the body's immune system. Bimekizumab, a new treatment, targets certain parts of the immune system involved in psoriasis. Studies testing bimekizumab in different phases showed it is safe and effective in treating psoriasis. Many patients taking bimekizumab had good results with mild side effects, and higher doses were well tolerated. When patients taking bimekizumab were followed for multiple years, the longitudinal study showed it worked well and continued to work. Bimekizumab works well for psoriasis but might help with similar immune-related conditions.

Correlation of transverse rotation of the spine using surface topography and 3D reconstructive radiography in children with idiopathic scoliosis.

PURPOSE: The relationship between axial surface rotation (ASR) measured by surface topography (ST) and axial vertebral rotation (AVR) measured by radiography in the transverse plane is not well defined. This study aimed to: (1) quantify ASR and AVR patterns and their magnitudes from T1 to L5; (2) determine the correlation or agreement between the ASR and AVR; and (3) investigate the relationship between axial rotation differences (ASR-AVR) and major Cobb angle. METHODS: This is a retrospective study evaluating patients (age 8-18) with IS or spinal asymmetry with both radiographic and ST measurements. Demographics, descriptive analysis, and correlations and agreements between ASR and AVR were evaluated. A piecewise linear regression model was further created to relate rotational differences to Cobb angle. RESULTS: Fifty-two subjects met inclusion criteria. Mean age was 14.1 ± 1.7 and 39 (75%) were female. Looking at patterns, AVR had maximal rotation at T8, while ASR had maximal rotation at T11 (r = 0.35, P = .006). Cobb angle was 24.1° ± 13.3° with AVR of - 1° ± 4.6° and scoliotic angle was 20.9° ± 11.5° with ASR of - 2.3° ± 6.6°. (ASR-AVR) vs Cobb angle was found to be very weakly correlated with a curve of less than 38.8° (r = 0.15, P = .001). CONCLUSION: Our preliminary findings support that ASR measured by ST has a weak correlation with estimation of AVR by 3D radiographic reconstruction. This correlation may further help us to understand the application of transverse rotation in some clinical scenarios such as specific casting manipulation, padding mechanism in brace, and surgical correction of rib deformity.

3D Back Contour Metrics in Predicting Idiopathic Scoliosis Progression: Retrospective Cohort Analysis, Case Series Report and Proof of Concept.

Adolescent Idiopathic Scoliosis is a 3D spinal deformity commonly characterized by serial radiographs. Patients with AIS may have increased average radiation exposure compared to unaffected patients and thus may be implicated with a modest increase in cancer risk. To minimize lifetime radiation exposure, alternative imaging modalities such as surface topography are being explored. Surface topography (ST) uses a camera to map anatomic landmarks of the spine and contours of the back to create software-generated spine models. ST has previously shown good correlation to radiographic measures. In this study, we sought to use ST in the creation of a risk stratification model. A total of 38 patients met the inclusion criteria for curve progression prediction. Scoliotic curves were classified as progressing, stabilized, or improving, and a predictive model was created using the proportional odds logistic modeling. The results showed that surface topography was able to moderately appraise scoliosis curvatures when compared to radiographs. The predictive model, using demographic and surface topography measurements, was able to account for 86.9% of the variability in the future Cobb angle. Additionally, attempts at classification of curve progression, stabilization, or improvement were accurately predicted 27/38 times, 71%. These results provide a basis for the creation of a clinical tool in the tracking and prediction of scoliosis progression in order to reduce the number of X-rays required.

Pharmacogenomic testing for CYP2C19 and CYP2D6 in cyclic vomiting syndrome.

BACKGROUND: Amitriptyline (AT) is recommended as first-line prophylactic therapy in patients with cyclic vomiting syndrome (CVS). However, significant side effects limit its use and dosing is based on trial and error. Though the Clinical Pharmacogenetic Implementation Consortium (CPIC) Guidelines recommend dosing for AT based on CY2D6 and CYP2C19 genotype profile, this is not followed in clinical practice. METHODS: This pilot study determined CYP2C19 and CYP2D6 genotypes and ascertained its association with adverse drug reactions (ADRs), clinical response, and serum concentration of AT and nortriptyline in a well-characterized cohort of adults with CVS. KEY RESULTS: Of 46 subjects with CVS, age 33 ± 12 years, 61% female, 85% Caucasian, a third (33%) had normal CYP2C19 metabolizer status, while 4% were poor, and 43% were ultrarapid metabolizers. Most (61%) had normal CYP2D6 genotype while 9% were poor and 2% were ultra-rapid metabolizers. There was no statistically significant association between genotype and ADRs, clinical response or serum drug concentration. There was a trend towards significance between genotype and clinical response, with 64% of responders having normal CYP2D6 metabolism versus 36% of nonresponders (p = 0.06). ADRs were encountered in 46% of patients with 28% discontinuing the medication as a result. CONCLUSIONS AND INFERENCES: A subset of patients with CVS have dysfunctional alleles of CYP2C19 and CYP2D6. Larger prospective studies to evaluate the clinical impact of pharmacogenomic testing in CVS are needed. This has the potential to optimize clinical management, predict ADRs and allow for personalized therapy.

Threat of shock increases distractor susceptibility during the short-term maintenance of visual information.

BACKGROUND: Work on anxiety related attention control deficits suggests that elevated arousal impacts the ability to filter out distractors. To test this, we designed a task to look at distractor suppression during periods of threat. We administered trials of a visual short-term memory (VSTM) task, during periods of unpredictable threat, and hypothesized that threat would impair performance during trials where subjects were required to filter out large numbers of distractors. METHOD: Experiment 1 involved fifteen healthy participants who completed one study visit. They performed four runs of a VSTM task comprising 32 trials each. Participants were presented with an arrow indicating left or right, followed by an array of squares. They were instructed to remember the target side and disregard the distractors on the off-target side. A subsequent target square was shown, and participants indicated whether it matched one of the previously presented target squares. The trial conditions included 50% matches and 50% mismatches, with an equal distribution of left and right targets. The number of target and distractor squares varied systematically, with high (4 squares) and low (2 squares) target and distractor conditions. Trials alternated between periods of safety and threat, with startle responses recorded using electromyography (EMG) following white noise presentations. Experiment 2 involved twenty-seven healthy participants who completed the same VSTM task inside an MRI scanner during a single study visit. The procedure mirrored that of Experiment 1, except for the absence of white noise presentations. RESULTS: For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. However, results suggested that the white noise probes interfered with performance. For Experiment 2, we found that both accuracy was affected by threat, such that distractor load negatively impacted accuracy only in the threat condition. CONCLUSION: Overall, these findings suggest that threat affects distractor susceptibility during the short-term maintenance of visual information. The presence of threat makes it more difficult to filter out distracting information. We believe that this is related to hyperarousal of parietal cortex, which has been observed during unpredictable threat.

Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration.

Volumetric muscle loss (VML) is a traumatic injury where at least 20% of the mass of a skeletal muscle has been destroyed and functionality is lost. The standard treatment for VML, autologous tissue transfer, is limited as approximately 1 in 10 grafts fail because of necrosis or infection. Tissue engineering strategies seek to develop scaffolds that can regenerate injured muscles and restore functionality. Many of these scaffolds, however, are limited in their ability to restore muscle functionality because of an inability to promote the alignment of regenerating myofibers. For aligned myofibers to form on a scaffold, myoblasts infiltrate the scaffold and receive topographical cues to direct targeted myofiber growth. We seek to determine the optimal pore size for myoblast infiltration and differentiation. We developed a method of tuning the pore size within collagen scaffolds while inducing longitudinal alignment of these pores. Significantly different pore sizes were generated by adjusting the freezing rate of the scaffolds. Scaffolds frozen at -20 °C contained the largest pores. These scaffolds promoted the greatest level of cell infiltration and orientation in the direction of pore alignment. Further research will be conducted to induce higher levels of myofiber formation, to ultimately create an off-the-shelf treatment for VML injuries.

Interleaved TMS/fMRI shows that threat decreases dlPFC-mediated top-down regulation of emotion processing.

Background: The right dorsolateral prefrontal cortex (dlPFC) has been indicated to be a key region in the cognitive regulation of emotion by many previous neuromodulation and neuroimaging studies. However, there is little direct causal evidence supporting this top-down regulation hypothesis. Furthermore, it is unclear whether contextual threat impacts this top-down regulation. By combining TMS/fMRI, this study aimed to uncover the impact of unpredictable threat on TMS-evoked BOLD response in dlPFC-regulated emotional networks. Based on the previous findings linking the dlPFC to the downregulation of emotional network activity, we hypothesized TMS pulses would deactivate activity in anxiety expression regions, and that threat would reduce this top-down regulation. Methods: 44 healthy controls (no current or history of psychiatric disorders) were recruited to take part in a broader study. Subjects completed the neutral, predictable, and unpredictable (NPU) threat task while receiving TMS pulses to either the right dlPFC or a control region. dlPFC targeting was based on data from a separate targeting session, where subjects completed the Sternberg working memory (WM) task inside the MRI scanner. Results: When compared to safe conditions, subjects reported significantly higher levels of anxiety under threat conditions. Additionally, TMS-evoked responses in the left insula (LI), right sensory/motor cortex (RSM), and a region encompassing the bilateral SMA regions (BSMA) differed significantly between safe and threat conditions. There was a significant TMS-evoked deactivation in safe periods that was significantly attenuated in threat periods across all 3 regions. Conclusions: These findings suggest that threat decreases dlPFC-regulated emotional processing by attenuating the top-down control of emotion, like the left insula. Critically, these findings provide support for the use of right dlPFC stimulation as a potential intervention in anxiety disorders.

The maintenance of complex visual scenes in working memory may require activation of working memory manipulation circuits in the dlPFC.

Past research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing, 1,2,3 in addition to working memory 4, 5 . Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, researchers designed an experiment that looked at working memory performance during fMRI under both emotional and non-emotional task conditions. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth 6 . Results showed a significant main effect of the 'sort' condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. These results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these results show that the dlPFC is clearly implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks.

Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients.

Alterations in cerebral glucose metabolism can be indicative of both normal and pathological aging processes. In this retrospective study, we evaluated global and regional neurological glucose metabolism in 73 healthy individuals (mean age: 35.8 ± 13.1 years; 82.5% female) using 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). This population exhibited a low prevalence of comorbidities associated with cerebrovascular risk factors. We utilized 18F-FDG-PET/CT imaging and quantitative regional analysis to assess cerebral glucose metabolism. A statistically significant negative correlation was found between age and the global standardized uptake value mean (SUVmean) of FDG uptake (p = 0.000795), indicating a decrease in whole-brain glucose metabolism with aging. Furthermore, region-specific analysis identified significant correlations in four cerebral regions, with positive correlations in the basis pontis, cerebellar hemisphere, and cerebellum and a negative correlation in the lateral orbital gyrus. These results were further confirmed via linear regression analysis. Our findings reveal a nuanced understanding of how aging affects glucose metabolism in the brain, providing insight into normal neurology. The study underscores the utility of 18F-FDG-PET/CT as a sensitive tool in monitoring these metabolic changes, highlighting its potential for the early detection of neurological diseases and disorders related to aging.