2026年 · 第02卷第03期

There is considerable controversy regarding the network systems underlying attention and consciousness. This communication reviews evidence suggesting that whole cortex mechanisms may complement network and regional effects on these functions. These diffuse changes could be assessed with waveform analysis, as used in statistical physics. Doing this might clarify the nature of mechanisms underlying attention, consciousness, and other natural phenomena, and lead to new approaches to diagnosis and treatment.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterized by social communication deficits, restricted and repetitive behavioral patterns, and sensory abnormalities. In this review, we posit that the core ASD symptoms originate from impaired brain energy metabolism, specifically within astrocytes, which play a key role in glucose uptake, glycogen storage, and energetic support for neurons. Neuronal signaling depends on a continuous supply of adenosine triphosphate (ATP), and glucose constitutes the principal energy substrate of the brain. Therefore, disrupted glucose delivery or utilization can significantly affect ATP availability in neurons and other brain cells, which can influence brain development and function. We hypothesize that ASD may represent a form of "energy-saving adaptation", wherein the brain economizes energetically by deprioritizing higher-order, energy-intensive processes, such as social communication, adaptation to novel information, cognitive flexibility, and sensory integration, and preserves ATP for basic survival functions. Building upon a comprehensive synthesis of the relevant literature, we argue that deficits in cellular metabolism in the brain, and subsequent suboptimal ATP generation and/or utilization, underlie ASD symptomatology, regardless of etiology. The conceptualization of ASD as a disorder of brain energy metabolism could catalyze new research agendas via cross-pollination of findings from related fields such as diabetes-linked cognitive dysfunction, schizophrenia, bipolar disorder (BP), and other neuropsychiatric and neurological conditions that implicate brain energy metabolism as a key pathogenic factor.

Mild traumatic brain injury (mTBI) is a globally prevalent, albeit underdiagnosed, neurological condition. Current acute imaging guidelines predate advances in neuroimaging and digital health, and significant interinstitutional variability persists in imaging practices, follow-up strategies, and technology integration. This narrative review synthesizes contemporary evidence on the diagnostic evaluation measures and technology-assisted management of mTBI, providing clinicians with a practical perspective on the role of emerging imaging and digital health tools in optimizing diagnostic accuracy, monitoring strategies, and rehabilitation outcomes. Clinical guidelines and peer-reviewed studies published between 2000 and 2025 were identified via PubMed and Google Scholar using the following search terms: "mild traumatic brain injury," "concussion," "neuroimaging," "rehabilitation technology," and "post-concussion syndrome." The Canadian computed tomography Head Rule (CCHR) and New Orleans Criteria (NOC) provide validated acute imaging frameworks; however, both possess structural limitations in special populations, such as children, older adults, and anticoagulant users, for whom modified decision tools and thresholds are needed. Advanced neuroimaging techniques (diffusion tensor imaging [DTI], susceptibility-weighted imaging [SWI], functional magnetic resonance imaging [fMRI], magnetoencephalography [MEG], magnetic resonance spectroscopy [MRS], and quantitative electroencephalography [qEEG]) reveal microstructural, functional, and metabolic injury aspects that are imperceptible in conventional imaging, although most remain investigational, pending protocol standardization. Technology-assisted recovery approaches such as digital symptom tracking, wearable biosensors, telemedicine, virtual reality-based interventions, and artificial intelligence-driven training demonstrate promise across the rehabilitation care continuum; nevertheless, the paucity of high-quality trial data and nonexistent implementation standards limit clinical translation. In general, the focal limitation is variability across imaging protocols, guideline applicability, technology validation, and care access. Coordinated multicenter research, population-specific guideline development, and equitable implementation frameworks can actualize the potentiality of emerging neuroimaging and rehabilitation technologies in mTBI management.

Glaucoma has conventionally been characterized as an optic neuropathy resulting from the degeneration of retinal ganglion cells (RGCs) and axonal loss of the optic nerve head (ONH). However, accumulating data suggest that glaucoma extends beyond ocular effects and encompasses widespread alterations in the brain anatomy, connectivity, and energy metabolism. Therefore, this review aimed to consolidate the current understanding of altered brain metabolism in glaucoma and situate it within the broader context of bioenergetic susceptibility. We investigated the role of mitochondrial malfunction, oxidative stress, glial activation, and impaired axonal transport in the development of energy insufficiency along the retinocerebral axis. Additionally, this review examined the mechanisms by which metabolic deficiencies disrupt synaptic homeostasis and functional connections, potentially leading to neurodegeneration. Notably, this review does not argue for a single causal hierarchy by which metabolic failure universally initiates glaucoma. Rather, we frame bioenergetic insufficiency as a convergent vulnerability state and a downstream amplifier that can interact bidirectionally with established upstream stressors such as intraocular pressure (IOP)-related mechanical strain and neurovascular dysregulation. Particularly, we focused on the bidirectional relationship between mechanical stress associated with IOP and brain metabolic failure, along with evidence that metabolic abnormalities can emerge early and, in longitudinal experimental models, may be detectable before overt structural degeneration; however, the temporal sequence remains unclear because much of the evidence is cross-sectional. Accordingly, mechanistic causality in this review was primarily grounded in experimental/preclinical studies. In contrast, human neuroimaging and metabolomic findings are interpreted primarily as associative biomarkers that support but do not by themselves contribute to glaucomatous neurodegeneration. We also investigated novel diagnostic instruments such as metabolic imaging, cerebrospinal fluid (CSF) biomarkers, and plasma-derived metabolomic signatures, which could facilitate the preclinical identification of glaucomatous neurodegeneration. Furthermore, this review discusses the innovative therapeutic strategies aimed at brain metabolism, including mitochondrial stabilizers, ketone-based therapies, neurovascular modulators, and activity-oriented neurorehabilitation. Collectively, these insights provide an integrative framework in which glaucoma is viewed as an ocular neurodegenerative disease with measurable systemic and cerebral metabolic correlates that may modulate susceptibility and progression, without implying that metabolic failure is a universal primary trigger.

Background: Adenosine A2A receptor antagonists—istradefylline, preladenant, and tozadenant—are adjunctive therapies for motor fluctuations in Parkinson’s disease (PD). However, the comparative efficacy and safety of different agents and doses remain unclear. Methods: We conducted pairwise and dose-stratified network meta-analyses (NMA) of randomized controlled trials (RCTs) evaluating A2A antagonists regarding OFF time, ON time with troublesome dyskinesia, Unified Parkinson’s Disease Rating Scale Part III (UPDRS III) scores, and adverse events (AEs). Random-effects models using restricted maximum likelihood (REML) accounted for within- and between-study variability. Heterogeneity and inconsistency were assessed using τ2, I2, and Q statistics. Results: Pairwise meta-analysis showed significant reductions in OFF time versus placebo (mean difference [MD] = - 0.35; 95% confidence interval [CI]: [- 0.52, - 0.18]), with benefits for istradefylline (MD = - 0.29; 95% CI: [- 0.57, - 0.01]) and preladenant (MD = - 0.36; 95% CI: [- 0.56, - 0.15]); tozadenant was ineffective. NMA of OFF time (11 RCTs, 45 comparisons) found modest benefits for istradefylline 20 mg (MD = - 0.33; 95% CI: [- 0.66, 0.01]) and 40 mg (MD = - 0.47; 95% CI: [- 0.83, - 0.11]) with moderate-certainty evidence; preladenant and tozadenant showed low or very low certainty. For ON time with troublesome dyskinesia (6 studies, n = 1439), istradefylline 40 mg significantly increased ON time (MD = 0.61; 95% CI: 0.14-1.07), while 20 mg showed a positive trend; preladenant was ineffective. UPDRS III scores (8 RCTs, 31 comparisons) showed no significant improvements, with substantial heterogeneity (τ2 = 2.107; I2 = 85.0%). In safety analyses (13 studies, n = 5364), istradefylline 20 mg (OR = 1.34; 95% CI: 1.04-1.72) and preladenant 10 mg (OR = 1.37; 95% CI: 1.05-1.80) increased AEs; other doses were similar to placebo. The network heterogeneity was low (I2 = 10.1%). Conclusions: Istradefylline 40 mg provided modest improvements in the OFF and ON times with moderate-certainty evidence; preladenant and tozadenant showed limited or uncertain efficacy. No agents significantly improved UPDRS III scores, and some doses increased AEs. Evidence is constrained by heterogeneity, imprecision, and methodological limitations. High-quality, large RCTs are needed to clarify dose-response effects and confirm the clinical role of A2A antagonists in PD.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease with four-repeat (4R)-tau pathology. Recent studies suggest tau deposition overlaps with iron dysregulation in vulnerable brain regions. We used second-generation fluorine-18 labeled PI-2620 tau positron emission tomography (18F-PI-2620 tau PET) imaging and quantitative susceptibility mapping (QSM) to explore intrinsic interactions during neurodegeneration in the PSP brain. Methods: Seventeen patients with PSP (including 11 PSP-Richardson’s syndrome [PSP-RS] subtype) and eight healthy controls underwent 18F-PI-2620 PET and 3.0 T brain magnetic resonance imaging (MRI) scans. Whole-brain tau uptake was analyzed using standardized uptake value ratio (SUVR) with cerebellum as the reference. Iron content in subcortical regions was quantified using mean susceptibility values (MSV). The effect of QSM on the association between tau uptake and brain volume was tested using mediation analysis. Results: PSP and PSP-RS patients showed increased tau uptake in bilateral globus pallidus (GP) and right subthalamic nucleus (STN), and reduced uptake in left caudate nucleus (CN) (all P <0.05). Tau uptake in STN, red nucleus (RN), and dentate nucleus (DN) in PSP yielded a unique internal correlation network (all P <0.05) and correlated with severity of patients’ non-motor symptoms (all P <0.01). Greater susceptibility was observed in bilateral CN, putamen (PUT), GP, STN, RN, and substantia nigra (SN) (all P <0.05). Structural atrophy of brain regions, including basal ganglia (all P <0.01), was found in brain volume analysis in both PSP and PSP-RS groups. Regional analysis revealed associations between tau-SUVR, QSM-MSV, and volume in multiple vulnerable regions. Mediation analysis showed that effects of tau burden on structural atrophy in left CN and right PUT could be partially or fully explained by iron accumulation. Conclusions: These findings show the strong relationships among 4R tauopathy, iron dysregulation, and structural atrophy in vivo. Advanced neurodegeneration may be explained by tau-dependent, iron-dependent, or synergistic mechanisms, providing insights into PSP pathogenesis.

Background: Grip strength is a reliable marker of overall muscle strength and nutritional status. This study aimed to investigate the relationship between year-to-year grip strength variability and subsequent cognitive trajectories among middle-aged and older Chinese adults. Methods: We analyzed longitudinal grip strength data from the first three waves (W1-W3) of the China Health and Retirement Longitudinal Study (CHARLS). Annual grip strength variations were assessed using the Variance Independent of Mean (VIM). To analyze the developmental trajectories of different subgroups in the longitudinal data, group-based trajectory modeling (GBTM) was used to systematically investigate age-related changes in cognitive aging trajectories. Associations between trajectory membership and grip strength variability were examined using multinomial logistic regression. Results: The study included 4205 participants aged 50-75 years, whose longitudinal cognitive trajectories were classified into four distinct patterns according to global cognitive performance. The largest subgroup, the "persistently high" trajectory (n = 1406, 33.4 %), maintained superior cognitive function throughout the follow-up period. A "fluctuating moderate" trajectory was identified in 976 participants (23.2 %), while the remaining participants were nearly evenly split between "persistently moderate" (n = 937, 22.3 %) and "persistently low" (n = 886, 21.1 %) trajectories, demonstrating stable intermediate and poor cognitive function, respectively. Participants exhibiting greater grip strength variability had significantly increased odds (odds ratio [OR]: 2.37, 95 % confidence interval [CI]: 1.69-3.30) of belonging to the "persistently low" trajectory of global cognitive function. Conclusions: The cumulative evidence from these analyses demonstrates that sustaining stable muscle strength over time is strongly associated with favorable cognitive aging outcomes. Elevated variability in grip strength was significantly linked to a higher likelihood of following a persistently low cognitive trajectory, regardless of overall trends or baseline values. Participants with high baseline grip strength who also exhibited low but increasing variability over time appeared to maintain a "persistently high" cognitive trajectory.