BackgroundChronic pain (CP) is a public health challenge recognized as involving large-scale functional brain dysregulation. Acupuncture is widely used as a non-pharmacological intervention for CP, yet its central mechanisms remain incompletely understood. fMRI provides an approach for investigating acupuncture-related brain alterations in CP.MethodsEight databases were searched from inception to March 27, 2025 for fMRI studies investigating acupuncture’s central effects in CP. Eligible studies included randomized controlled trials and observational studies involving migraine, knee osteoarthritis, fibromyalgia, sciatica, chronic shoulder pain, chronic neck pain, cervical spondylosis, chronic low back pain, and lumbar disk herniation. Data on characteristics, acupuncture protocols, neuroimaging findings, and outcomes were extracted and narratively synthesized. Reporting quality of acupuncture interventions was assessed using STRICTA, risk of bias of randomized controlled trials using RoB 2, and methodological quality of observational studies using the Newcastle–Ottawa Scale.ResultsA total of 64 studies were included. CP was characterized by widespread functional brain abnormalities, mainly involving the default mode network, sensorimotor network, and pain- and emotion-related regions such as the anterior cingulate cortex, precuneus, insula, and thalamus. Across longitudinal and controlled analyses, acupuncture-related brain changes were most consistently reflected in altered functional connectivity, local neural synchrony, and regional spontaneous activity. Functional connectivity findings suggested a potentially ACC-centered circuit pattern, whereas regional homogeneity findings revealed bidirectional modulation across multiple brain regions. Comparative evidence further indicated that VA, SA, and EEA may engage partially overlapping but distinct neural processes. Reporting of core acupuncture protocol components was generally adequate, whereas methodological quality remained heterogeneous.ConclusionCurrent fMRI evidence suggests that CP involves large-scale network-level functional imbalance and that acupuncture may be associated with modulation of key abnormal nodes and circuits related to pain perception, sensory processing, and emotional regulation. The available evidence supports a cautious interpretation that acupuncture-related brain effects may predominantly reflect a state-dependent recalibration of dysregulated brain networks. Future studies should prioritize large-sample, multicenter, longitudinal, and multimodal designs, together with rigorous control settings and more rigorous, externally validated machine learning-based prediction studies, to better distinguish differential central effects across intervention conditions and advance mechanism-informed personalized acupuncture in CP management.
Associations between serum tumor necrosis factor-alpha, hippocampal-prefrontal-ventricular volumes, and clinical profiles in schizophrenia: a biomarker and neuroimaging study in North Sumatera, Indonesia
IntroductionSchizophrenia is a neurodevelopmental disorder with systemic inflammation that is thought to play a role in its pathophysiology. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) has been reported to be dysregulated in individuals with schizophrenia, but its relationship with brain volume changes remains inconsistent. This study aimed to analyze differences in TNF-α levels and brain volume (hippocampus, prefrontal cortex, and lateral ventricles) and their correlations in schizophrenia patients compared to healthy controls.MethodsThis analytical cross-sectional investigation was conducted on 50 schizophrenia patients and 50 healthy Batak controls at the Prof. M. Ildrem Provincial Mental Hospital, Medan. Serum TNF-α levels were measured by ELISA, while brain structure volume was measured by 1.5 T MRI and analyzed using AnalyzePro software.ResultsTNF-α levels in the schizophrenia group were significantly lower (3.35 pg/dl) than in the control group (16.90 pg/dl). No significant differences in hippocampal and prefrontal cortex volume were found between the groups. However, lateral ventricle volume was significantly larger in schizophrenia. Correlation analysis showed a weak negative relationship between TNF-α and prefrontal cortex volume only in the schizophrenia group.DiscussionThe finding of low TNF-α in schizophrenia supports the complexity of immune dysfunction in schizophrenia, which may be influenced by medication or disease phase. Consistent ventricular enlargement reinforces previous neuroanatomical findings. The association of TNF-α with the prefrontal cortex only within the schizophrenia cohort indicates a specific interaction between inflammation and brain morphology in this patient population.ConclusionsThe findings support TNF-α dysregulation in schizophrenia, albeit at lower levels. Lateral ventricular enlargement was consistently found, while changes in hippocampal and prefrontal cortex volume may be more subtle in this population. The negative correlation between TNF-α and the prefrontal cortex in schizophrenia suggests a potential role for inflammation in the pathology of this brain region.
Multivariate age-related variations in quantitative MRI maps: widespread age-related differences revisited
This study applied multivariate ANOVA to investigate age-related microstructural changes in the brain tissues driven primarily by myelin, iron, and water content, as observed in MRI (semi-)quantitative R1, R2*, MTsat and PD maps. This is effectively a re-analysis of the data analyzed in a univariate way in a previous publication. Voxel-wise analyses were performed on gray matter (GM) and white matter (WM), in addition to region of interest (ROI) analyses. The multivariate approach identified brain regions showing coordinated alterations in multiple tissue properties and demonstrated bidirectional correlations between age and all examined modalities in various brain regions, including the caudate nucleus, putamen, insula, cerebellum, lingual gyri, hippocampus, and olfactory bulb. The multivariate model was more sensitive than univariate analyses, as evidenced by detecting a larger number of significant voxels within clusters in the supplementary motor area, frontal cortex, hippocampus, amygdala, occipital cortex, and cerebellum bilaterally. Though when cross validating the results by splitting the data into 2 subsets, sensitivity is strongly reduced, even more so for the multivariate approach. The examination of normalized, smoothed, and z-transformed maps within the ROIs revealed concurrent age-dependent alterations in myelin, iron, and water content. These findings contribute to our understanding of age-related brain differences and provide insights into the underlying mechanisms of aging. The study emphasizes the importance of multivariate analysis for detecting subtle microstructural changes associated with aging when dealing with multiple quantitative MRI parameter maps.
An Augmented Reality Audio-Motor Training Game for Improving Speech-in-Noise Perception: Single-Arm Pilot Feasibility Study
Background: Difficulty understanding speech in noisy environments is a primary challenge of hearing impairment, inadequately addressed by hearing aids alone. While auditory training can enhance selective attention and speech perception, current digital programs face poor user adherence and lack realistic 3D spatial audio. Objective: This pilot study evaluated the feasibility, usability, and preliminary efficacy of ARIA (Augmented Reality Immersive Auditory training), a handheld mobile intervention that provides gamified at-home auditory training to middle-aged adults via earbud-delivered spatial audio. Methods: In this single-arm, pre-post–follow-up pilot study, 11 adults (mean age 53.0, SD 3.0 y) with functional hearing not requiring amplification completed a 4-week at-home training program using ARIA on provided devices (iPhone 14 Pro, AirPods Pro 2). Speech-in-noise perception was assessed via the Korean Matrix Sentence Test at baseline, 4 weeks, and 8 weeks at 3 signal-to-noise ratios (SNRs; 0 dB, −6 dB, and −9 dB, respectively). Feasibility, usability (System Usability Scale), user experience (Player Experience of Need Satisfaction), in-game performance, and qualitative feedback were collected. Results: Protocol completion was 100% (11/11), demonstrating technical feasibility. Exploratory efficacy analyses revealed statistically significant speech-in-noise improvements posttraining across all conditions (0 dB: =3.43, =.02; −6 dB: =5.34, <.001; −9 dB: =4.34=.004). Gains were maintained at the 8-week follow-up. In-game localization improvements correlated significantly with speech perception gains at −6 dB SNR (ρ=0.639; =.03) and −9 dB SNR (ρ=0.612; =.045). User experience showed mixed results: the mean System Usability Scale score was 70.2 (SD 19.6; range 47.5‐92.5), reflecting substantial individual differences in usability perception. While 72% (n=8) reported difficulties with the augmented reality (AR) environmental setup, 63% reported genuine mastery-driven engagement with core gameplay. Thematic analysis revealed a dissociation between peripheral usability challenges (setup friction, “homework” characterization due to protocol structure) and successful engagement with the training paradigm itself. Conclusions: This pilot demonstrated the feasibility of AR-based audio-motor training for at-home delivery and revealed encouraging preliminary efficacy signals, warranting progression to controlled efficacy trials. Formative findings identified specific usability refinements needed for broader implementation, particularly streamlining AR setup while preserving the core gameplay elements that successfully fostered competence and engagement. These insights provide clear guidance for platform optimization and randomized controlled trial design.
1H-MRS brain metabolites as biomarkers of high-altitude hypobaric hypoxia following mild traumatic brain injury in mice
Introduction and objectivePopulations at high altitude (HA) face a higher incidence and severity of traumatic brain injury (TBI). This pilot study utilized longitudinal 1H-MRS to identify neurochemical biomarkers of HA adaptation and the subsequent metabolic response to mild TBI (mTBI).MethodsMale C57BL/6J mice were exposed to simulated HA (5,000 m) or sea level (SL) for 12 weeks. Following adaptation, a unilateral mTBI was induced via closed head injury (CHI). Mice were then monitored for an additional 2 weeks at HA (total duration of 14 weeks). In vivo1H-MRS spectra (7 T) were collected from the frontal cortex, hippocampi, and cerebellum at weeks 0, 4, 12 to assess HA adaptation. Following the CHI, subsequent measurements were collected at week 12 (post-injury) and week 14 to monitor longitudinal neurochemical responses to the mTBI.ResultsChronic HA exposure induced significant reductions in myo-inositol (Ins) and total choline (tCho) in the hippocampus, establishing a baseline of metabolic fragility that sensitized the brain to subsequent traumatic insult. Post-mTBI, the HA group exhibited a profound “metabolic crisis,” characterized by significantly lower tCho and failed recovery of total N-acetylaspartate (tNAA) compared to SL controls. Total creatine (tCr) was the most acutely affected metabolite, underscoring a depletion of the bioenergetic reserve.ConclusionChronic hypobaric hypoxia fundamentally alters baseline brain metabolism and impairs the neurochemical recovery from mTBI. These findings suggest that standard recovery protocols may be insufficient for HA-adapted populations and highlight 1H-MRS as a critical tool for detecting “invisible” metabolic vulnerability in extreme environments.
Steroid receptor coactivator-1: integrating steroid hormone signals to regulate brain function and disease
Steroid receptor coactivator-1 (SRC-1), also known as nuclear receptor coactivator-1 (NCOA1), represents the first identified member of the p160 nuclear receptor coactivator family and plays a pivotal role in integrating steroid hormone signals, regulating gene transcription, and maintaining neural homeostasis in the central nervous system (CNS). SRC-1 exhibits region-specific, cell-type-specific, and sexually dimorphic expression patterns in the brain, with prominent distribution in key regions including the hippocampus, cerebral cortex, hypothalamus, and amygdala. Functional studies demonstrate that SRC-1 participates in diverse neural functions such as learning and memory, energy metabolism, emotional regulation, and reproductive behavior through modulation of synaptic plasticity-related genes, neurotrophic factors, and metabolic pathways. Aberrant SRC-1 expression is closely associated with neurodegenerative diseases, autism spectrum disorders, and glioblastoma. This review systematically summarizes the molecular structure, expression characteristics, physiological functions of SRC-1, and its roles in neurological disorders, while discussing its potential applications as a diagnostic biomarker and therapeutic target.
Beyond distress relief: the Anhedonic Subtype of nonsuicidal self-injury and the imperative for Positive Affect Treatment
This perspective article argues that the theoretical landscape of nonsuicidal self-injury (NSSI) has long been stabilized by the “hydraulic” model of Automatic Negative Reinforcement, which conceptualizes self-harm primarily as a mechanism to down-regulate aversive hyper-arousal. While this framework successfully elucidates the etiology of self-injury driven by high-intensity negative affect, it fails to account for a substantial, treatment-resistant phenotype: adolescents driven by profound anhedonia and ventral striatal hypofunction. This perspective article argues for the formal recognition of an “Anhedonic Subtype” of NSSI. Synthesizing recent epidemiological data identifying “emptiness” as a central symptom network bridge, alongside neurobiological evidence of reward blunting, we posit that for this subtype, NSSI functions not as a sedative, but as a mechanism of “forced activation.” We propose a preliminary differential diagnostic framework distinguishing defensive dissociation from anhedonic deficit and outline the theoretical rationale for exploring a shift in clinical intervention from distress tolerance toward positive affect up-regulation. The clinical utility of this framework remains to be evaluated in future empirical research.
Resting-State Functional Connectivity of the Amygdala and Hippocampus in PTSD: Results From the PGC-ENIGMA PTSD Working Group
American Journal of Psychiatry, Volume 183, Issue 5, Page 333-342, May 01, 2026.
Manual therapy ameliorates neuromuscular dysfunction in spastic model rat: involvement of the C-Fiber-mediated CaMKII pathway
BackgroundThis study investigated whether manual therapy applied to tendon organs ameliorated neuromuscular dysfunction in rats with spasticity induced by upper motor neuron injury associated with spastic cerebral palsy, and analyzed the potential involvement of the C-fiber-mediated CaMKII signaling pathway.MethodsMale rats were used to establish palsy models and divided into groups: Control, Model, Manual Therapy (MT), Capsaicin Treatment, Sham, CaMKII Inhibitor, and DMSO Solvent groups. Except for Control, all underwent pyramidal-tract destruction. After modeling, the MT group received manual therapy on the left-lower leg tendon organs. The Capsaicin group underwent sciatic nerve capsaicin treatment for C-fiber block on days 2 and 7; the Sham group had sciatic nerve exposure only. Both received daily manual therapy intervention for 14 days. The CaMKII Inhibitor and DMSO Solvent groups received intrathecal injections every 2 days (7 times total) without manual intervention. Spasticity-related behavioral indices, molecular expression, and neurotransmitter levels were assessed.ResultsManual therapy reduced the neurological deficit scores and muscle spasticity scores of model rats, improved the pathological morphology of the pyramidal tract and skeletal muscle, and regulated the expression of key molecules and neurotransmitters in the spinal cord and hippocampus. The therapeutic effects of manual therapy were significantly attenuated after C-fiber blockage, and although CaMKII inhibition could partially mimic the neuromodulatory effects of manual therapy, its efficacy in alleviating spasticity was inferior to that of manual-therapy intervention.ConclusionManual therapy appears to regulate CaMKII signaling via C-fiber afferent pathways to ameliorate neuromuscular dysfunction in a rat model of spasticity induced by pyramidal-tract lesion, thereby providing experimental evidence for the clinical application of optimized manual therapy parameters in the management of spasticity in patients with cerebral palsy.
Dissociation: Signs and Causes in Children
When people use the word dissociation, it can sound alarming. You may have seen it on social media, heard your child mention it, or noticed your child seeming “checked out” and wondered if that’s what’s happening. Dissociation can be confusing because it exists on a spectrum — from everyday experiences like daydreaming to more serious symptoms that may signal that a child is overwhelmed or struggling. The good news is that dissociation is often a temporary coping mechanism, and when it does become a problem, there are effective ways to help.
What is dissociation?
In simple terms, dissociation is a kind of mental disconnection. “When I think of dissociation, I think of there being some sort of disconnect between an individual and their sense of self, or a period of time that you later can’t recall, or feeling like you’re disconnected from your body,” says Lauren Allerhand, PsyD, a clinical psychologist at the Child Mind Institute and co-director of its DBT program.
Some kids describe dissociation as feeling spaced out, numb, or disconnected from their body or surroundings. Others say they feel like they’re watching themselves from outside their body, or that the world around them doesn’t feel real. “There’s some period of time where your normal sense of flow is disrupted,” Dr. Allerhand explains.
Is dissociation normal?
In its mildest form, dissociation is a commonplace occurrence. Kids might daydream in class, zone out during something boring like a long car trip, or feel detached when they are overwhelmed in some way. These experiences are usually not a cause for concern. “Our brains do a really good job of protecting ourselves,” Dr. Allerhand says. “Sometimes our brains develop strategies to protect us that are healthy, and other times they develop strategies that might work in short bursts but become less helpful if they happen too much.”
When dissociation happens often, or interferes with daily life, it may signal that a child is struggling with something more serious than ordinary, intermittent stress. “If it’s happening all the time, it’s less effective as a coping mechanism” because of the toll it can take when there is memory loss, confusion, and feeling disconnected to the self, she explains.
What does dissociation feel like?
Children and teens may describe dissociation differently. Some say they feel:
- Like they’re in a dream
- Emotionally numb
- Detached from their body
- Like they’re watching themselves in a movie
- Like things around them aren’t real
“Kids might say they feel like a robot. Everything feels fake around them,” Dr. Allerhand says. “Younger children may not have the words to describe what they’re experiencing. Instead, parents might notice their child seems unusually quiet, unresponsive, or ‘not themselves.’”
Why do kids dissociate?
Dissociation is often linked to stress or overwhelming emotions — kids may dissociate when they feel unable to cope with what’s happening around them. “This could be a response to any sort of highly intense emotion or experience,” Dr. Allerhand says, such as:
- Trauma
- Anxiety or panic
- Intense emotions
- Depression
- Major life changes
- Overwhelming stress
“It’s another way of coping with stress or trauma,” says Tanvi Bahuguna, PsyD, a clinical psychologist at the Child Mind Institute who specializes in trauma and mood disorders. “There’s this psychological process that helps them disconnect from overwhelming pain.” Some kids dissociate during panic attacks or periods of intense anxiety. Children who have experienced significant adversity may be more likely to dissociate. These experiences can include:
- Abuse
- Neglect
- Family instability (housing instability, domestic violence, addiction)
- Loss of a family member, especially through violence or suicide
Still, experts are quick to note that dissociation doesn’t automatically mean a child has experienced trauma or has a serious disorder. “There are lots of exits on this highway before we’re at a dissociative disorder,” Dr. Allerhand says, adding that a full-blown dissociative disorder is very rare in children.
Mild vs. serious dissociation
It can be hard to recognize when a child is experiencing more serious dissociation because it doesn’t always look different from daydreaming or inattention. One key difference is distress. “Spacing out or not paying attention is not often experienced as distressing,” Dr. Allerhand says. Moderate or serious dissociation “is often somewhat distressing.” Kids who are daydreaming are still connected to themselves and their surroundings; kids who are experiencing more serious dissociation may feel cut off from their body, emotions, or reality altogether.
Using grounding techniques for dissociation
If you think your child may be dissociating, the most important thing you can do is not panic or try to get your child to “snap out of it.” “The number one thing a parent can do is stay as calm as possible,” Dr. Bahuguna says. Speak gently, use short sentences, and reassure your child that they’re safe. Saying your child’s name and reminding them you’re there can help them reconnect.
Grounding techniques can also bring kids back into the present moment. One common method is called the 5-4-3-2-1 technique: Ask the child to name five things they can see, four things they can feel, three things they can hear, two things they can smell, one thing they can taste or imagine tasting. Other grounding strategies include:
- Deep breathing
- Squeezing a stress ball
- Holding something cold
- Gently moving the body
If you find your child often dissociates, Dr. Allerhand recommends helping them make a plan for it. During a calm moment, talk with your child about what they find helpful. “I noticed that this is happening. How can I help you when this is happening?” she suggests asking. Having a plan in advance makes it easier to respond in the moment — and in the meantime, stay nearby and make sure your child is safe until the episode passes.
When should parents seek help for a child who dissociates?
If dissociation is frequent, distressing, or associated with changes in your child’s functioning, seeking professional support is appropriate. “If something dissociative happens, and there’s a really big change in your child’s functioning, then I would be concerned,” Dr. Allerhand says.
Signs it may be time to reach out include:
- Memory gaps after the episode
- Noticeable personality changes
- Difficulty at school
- Withdrawal from friends or activities
- Significant distress or confusion
A good place to start would be talking to your pediatrician, who may refer you to a mental health professional. “If your child is displaying behaviors that seem out of the ordinary, you should trust your instincts,” Dr. Allerhand says.
How to identify dissociation
To determine whether a child is dissociating, a mental health professional gathers information from multiple sources, including parents, the child, and sometimes teachers, asking about the child’s behaviors, history, and any recent stressors or changes in behavior.
“The first thing would be a structured diagnostic interview with a qualified clinician,” Dr. Allerhand explains. “Parents bring the history and describe the behavior, and then the clinician meets with the child.” Clinicians also consider whether dissociation might be a symptom of another condition, such as post-traumatic stress disorder, borderline personality disorder, anxiety (especially panic disorder), and depression.
“It’s really gathering history, meeting the child, observing the child, and figuring out what this cluster of behaviors leads to,” she says. It’s more frequent to find that dissociation is a result of another disorder than an actual dissociative disorder.
How is dissociation treated?
Treatment depends on what’s driving the dissociation. If trauma is involved, therapy may focus on helping the child process difficult experiences and build coping skills. Evidence-based approaches include trauma-focused cognitive behavioral therapy (TF-CBT) and eye movement desensitization and reprocessing (EMDR).
If anxiety or emotional overwhelm is the primary cause, treatment may focus on emotion regulation, grounding techniques, and identifying triggers and early warning signs. Therapy, such as dialectical behavior therapy (DBT), typically involves both children and parents, helping families recognize patterns and respond in supportive ways.
For more severe or persistent dissociation, treatment may happen in phases — beginning with safety and stabilization, then skill-building, and eventually, when appropriate, processing difficult experiences. “The goal is helping the child learn to cope with their experience and stay in their body,” Dr. Allerhand says.
What are dissociative disorders?
In children and teens, dissociation is usually a symptom of another condition. But in cases of very serious early trauma, abuse, or neglect, it can progress into a full-blown disorder. There are a number of dissociative disorders, including:
- Dissociative identity disorder (what was once called multiple personality disorder) involves two or more distinct personality states and gaps in memory and is typically linked to significant early trauma. Parents who search online may find alarming information, but Dr. Allerhand says this condition is very rare in kids.
- Dissociative amnesia involves gaps in memory that can’t be explained by ordinary forgetfulness — such as not remembering important personal information or periods of time — and is often associated with stressful or traumatic experiences.
- Depersonalization/derealization disorder involves feeling detached from oneself, as though watching yourself from outside your body, or feeling that the world around you isn’t real.
These disorders sometimes attract media attention, but they are extremely rare in children. What’s important for parents to know is that if you see dissociative behavior in a child, it’s most likely a normal coping mechanism for a child experiencing some stress or intense emotion. If it persists, is causing distress, or is interfering with a child’s life, it’s time to consult a pediatrician or mental health professional. Identifying what might be causing the behavior is the first step to getting appropriate treatment.
Frequently Asked Questions
Dissociation is a mental disconnection from your thoughts, feelings, body, or surroundings. Kids may feel spaced out, numb, or like they’re watching themselves from the outside, as if the world doesn’t feel real.
Common signs include feeling detached from the body, emotionally numb, or like you’re in a dream. Some kids seem unusually quiet or “not themselves,” while others have trouble recalling what happened during that time.
Dissociation is often a response to stress, anxiety, or overwhelming emotions. It can also be linked to trauma, major life changes (such as the sudden loss of a family member), or intense feelings the child doesn’t yet know how to manage.
Grounding techniques can help bring you back to the present moment, like naming what you see, hear, and feel, or focusing on breathing. Having a plan for what you will do the next time can make it easier to manage when it happens.
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