Non-Suicidal Self-Injury (NSSI) presents a significant public health challenge; however, its underlying neurobiological mechanisms remain insufficiently understood, limiting the development of targeted interventions. Emerging evidence suggests that NSSI exhibits core addictive features, such as compulsive urges and tolerance, which may be driven by dysfunctions in the brain’s reward circuitry. This review synthesizes current research on the neural overlaps between NSSI and addiction, specifically focusing on the dysregulation of the ventral striatum and prefrontal cortex. Based on this mechanistic framework, we propose the potential of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)—a high-dose, functional connectivity-guided transcranial magnetic stimulation protocol—as a precision treatment for NSSI. By targeting specific reward network deficits, SAINT may offer a novel, rapid-acting therapeutic strategy for patients who do not respond to conventional pharmacological or psychological interventions.
Case Report: Delirium and complications resulting from the abuse of compound liquorice tablets
BackgroundCompound liquorice tablets is a cough-suppressing compound formulation containing opium powder and liquorice. With the strict regulation of traditional opioids, this medication has emerged as a novel alternative for substance abuse due to its easy accessibility and low cost; however, its addiction potential and severe adverse complications remain underrecognized and insufficiently addressed in clinical practice.Case summaryThe patient is a 29-year-old male who began self-medicating with compound liquorice tablets for a dry cough after COVID-19 infection. His daily dosage gradually escalated to 200–600 tablets within two years, resulting in established drug dependence. Two days after discontinuing the medication, he developed delirium manifested as confusion, disorientation, visual hallucinations and psychomotor agitation, accompanied by palpitations, hypertension, tremors, rhinorrhea, vomiting, severe hypokalemia, and bilateral lower limb edema. Organic brain diseases were excluded by systematic examinations. According to the ICD-10 diagnostic criteria, he was diagnosed with opioid-induced mental and behavioral disorders, hypokalemia and hypertension. We implemented a benzodiazepine tapering regimen to control delirium and sympathetic excitation associated with withdrawal symptoms, combined with antidepressants and antipsychotics to improve mood, anxiety, and psychotic symptoms, Under the guidance of a cardiologist, we actively managing hypertension and correcting internal environmental disturbances. Following comprehensive management, the patient’s withdrawal symptoms and delirium resolved, with stable emotional state and blood pressure, resulting in successful withdrawal.ConclusionThis is the first reported case of delirium caused by withdrawal from compound liquorice tablets. It provides preliminary insights for clinical identification, diagnosis, and multidisciplinary management of dependence on compound liquorice tablets, as well as related withdrawal symptoms and complications. This case also alerts to the emerging risk of abuse associated with new substances such as compound liquorice tablets and underscores the need for stricter prescription controls and patient education regarding the risks of abuse.
Neurochemical-hemodynamic-electrophysiological coupling in the neonatal brain: a multimodal MRS-fMRI-EEG investigation
IntroductionInhibitory and excitatory neurotransmitter levels are linked to fast neuronal oscillations and infra-slow hemodynamic fluctuations, suggesting a shared excitation–inhibition (E/I) regulatory framework across measures. However, these relationships may differ in early development, when both excitatory and inhibitory cortical systems are undergoing substantial functional and structural maturation. Consequently, we hypothesize different functional coupling between neurochemical, electrophysiological, and hemodynamic proxies of E/I signaling in healthy full-term neonates compared to what has been observed in adults.MethodsTwenty-five healthy full-term neonates (mean postmenstrual age at study = 40.1 ± 1.4 weeks) underwent multimodal MRI and electroencephalography (EEG) recordings during natural resting-state to provide proxy measures of neural excitation and inhibition. These included frontal and occipital MRS measures of γ-aminobutyric acid (GABA+) and Glx (glutamate + glutamine) levels, and their ratio; EEG source-reconstructed power spectra decomposed into periodic beta (13–30 Hz) and gamma (30–45 Hz) features (center frequency and peak amplitude), relative to total band power and an aperiodic exponent; and infra-slow fMRI BOLD fluctuations (0.01–0.08 Hz) using amplitude of low-frequency fluctuations (mean and fractional ALFF). Crossmodal relationships were assessed using partial correlations controlling for age.ResultsOccipital GABA+ was negatively correlated with beta relative power (r = −0.64, p = 0.01) and fractional ALFF (r = −0.55, p = 0.048), while mean ALFF was negatively correlated with gamma center frequency (r = −0.99, p = 0.02). These relationships were not observed in the frontal cortex. Instead, frontal Glx positively correlated with beta peak amplitude (r = 0.87, p < 0.01) and negatively correlated with beta (r = −0.78, p = 0.02) and gamma (r = −0.79, p = 0.02) relative power, potentially reflecting the existence of regionally distinct maturational trajectories.DiscussionTogether, these preliminary findings suggest that commonly used neurochemical, oscillatory, and hemodynamic proxy measures of cortical excitatory and inhibitory processes may show only modest correspondence at birth, consistent with ongoing and hierarchal cortical development, leading to complex and asynchronous relationships between these measures.
Endocannabinoid system modulation in bruxism: a neurobiological hypothesis and translational model of ECS-targeted intervention
Bruxism is a multifactorial motor behavior of predominantly central origin, characterized by repetitive masticatory muscle activity and associated with dysregulation of dopaminergic, serotonergic, GABAergic, and glutamatergic pathways involved in motor control, emotional regulation, and stress responsivity. The endocannabinoid system (ECS) has emerged as a key homeostatic neuromodulator capable of integrating these neurotransmitter systems, thereby influencing pain processing, sleep–wake dynamics, and motor output. This article develops a neurobiological hypothesis based on a narrative integrative synthesis of clinical, experimental, and translational evidence regarding ECS involvement in the pathophysiology of bruxism. Findings from randomized clinical trials suggest that topical cannabidiol (CBD) may modulate motor neuron excitability and reduce pain-related outcomes, while case-based and experimental evidence supports the interaction between cannabinoid signaling and neural circuits implicated in motor control and behavioral regulation. Building on this evidence, we propose a hypothesis-driven translational model in which ECS-mediated neuromodulation may influence central mechanisms underlying bruxism, including motor pattern generation, stress responsivity, and nociceptive processing. Rather than providing prescriptive therapeutic recommendations, this model is intended as a hypothesis-generating construct that integrates current knowledge on ECS signaling within the broader neurobiology of motor control. Although heterogeneity in study design and outcome measures limits definitive conclusions, the available evidence supports the ECS as a plausible modulatory system in bruxism, with potential implications for future mechanistic and clinical research in centrally mediated motor disorders.
First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy
Huntington’s disease therapeutics have reached a historic milestone—the first patient has successfully received an experimental neural stem cell therapy at UCI Health. This groundbreaking dose marks the world’s first human trial of embryonic stem cell-derived neural stem cells for the devastating neurodegenerative disorder.
The treatment, performed in May at University of California Irvine (UCI) Health, represents the culmination of more than 12 years of laboratory research and eight years of clinical planning led by scientists and physicians at the University of California, Irvine. Researchers hope the treatment, known as hNSC-01, could eventually slow disease progression, protect vulnerable brain cells and potentially restore damaged neural circuits.
To date, the first participant has not reported any serious adverse effects, according to the clinical team. A second patient is expected to receive the therapy in July.
“This clinical trial highlights the important role that an interdisciplinary academic and clinical team, together with the HD families, plays in advancing medicine,” Leslie M. Thompson, PhD, clinical trial sponsor as well as the Donald Bren Professor of psychiatry and human behavior UC Irvine, told Inside Precision Medicine. “We are grateful to our patients and their incredible families for their bravery to provide hope for others with very few options.”
hNSC-01
Huntington’s disease, caused by a mutation in the huntingtin gene, destroys brain cells, causing involuntary movements, cognitive decline, and psychiatric symptoms that begin between 35 and 50 and worsen over time. Without a cure, the fatal disorder burdens patients and families emotionally, physically, and financially, often requiring daily and long-term care.
Current treatments for Huntington’s disease primarily focus on managing symptoms rather than altering the underlying disease process. Drugs such as tetrabenazine and deutetrabenazine can reduce involuntary movements known as chorea, while antidepressants, antipsychotics and mood stabilizers help address psychiatric symptoms. Physical therapy, speech therapy and occupational therapy can also improve quality of life. However, none of these approaches has been shown to slow or stop the progressive loss of neurons that drives the disease.
Over the past decade, researchers have pursued several experimental disease-modifying strategies. Among the most advanced are gene-targeting therapies designed to reduce production of the mutant huntingtin protein. These include antisense oligonucleotides (ASOs), which are delivered through repeated spinal injections, as well as RNA-targeting and gene-editing approaches intended to suppress or correct the faulty gene. While these strategies directly target the genetic cause of Huntington’s disease, clinical results have been mixed, and questions remain about long-term effectiveness, safety and the need for lifelong treatment.
The hNSC-01 neural stem cell therapy being tested at UCI Health takes a different approach. Rather than targeting the mutant gene itself, the therapy aims to protect vulnerable neurons, replace lost cells, rebuild damaged neural circuits and provide supportive factors that promote brain health.
The UCI researchers believe stem cell-based therapies may offer a new approach by addressing multiple aspects of the disease simultaneously. The experimental treatment, hNSC-01, consists of pluripotent neural stem cells derived from embryonic stem cells and manufactured through the UC Davis Good Manufacturing Practice facility.
Preclinical studies in animal models suggested the cells could perform several functions relevant to Huntington’s disease, including protecting existing neurons, replacing cells that have been lost, rebuilding damaged neural networks and releasing beneficial proteins such as brain-derived neurotrophic factor (BDNF). The cells were also shown to reduce harmful protein accumulations associated with neurodegeneration and demonstrated long-term safety in mice.
Unlike conventional drug therapies, the stem cells are delivered directly into the brain. During the approximately six-hour procedure, performed under general anesthesia, patients lie face down within an MRI scanner while neurosurgeons use a specialized stereotactic navigation and delivery system to implant the cells into the striatum, a deep brain structure heavily affected by Huntington’s disease.
The striatum plays a central role in motor control, decision-making, motivation and learning. Degeneration of this region contributes significantly to the hallmark symptoms of the disorder. The first intervention was delivered by UCI Health neurosurgeon Jefferson W. Chen, MD, and a multidisciplinary surgical team.
Tracking treatment impact
As a Phase Ib/IIa study, the trial’s primary objective is to evaluate safety. However, researchers will also track biomarkers and clinical indicators that may provide early clues about whether the treatment is affecting disease progression.
When asked which biomarkers would help identify how the therapy is working in patients, Thompson emphasized that current measurements are focused more on assessing treatment impact than revealing biological mechanisms. “We will be including HD relevant clinical endpoints and biomarkers, including NfL in plasma and NfL and PENK in CSF; however, these are geared to understanding whether the treatment is having a benefit to these outcome measures versus informing the mechanism of action,” Thompson said.
One of the most important early indicators will be whether disease-related biomarkers remain stable rather than continuing their expected decline. “The earliest sign first and foremost is safety in this initial trial,” Thompson said. “Initial signs that the therapy could be meaningfully altering disease progression would be if the blood-based or CSF-based biomarkers do not show progression.”
Reaching the point of treating the first patient required overcoming a series of scientific, manufacturing and logistical hurdles. According to Thompson, selecting the optimal cell line was among the most significant challenges, testing multiple cell lines in vitro and in vivo.
Researchers also had to establish quality-control standards for the final therapeutic product and create Good Manufacturing Practice cell banks following extensive testing in Huntington’s disease mouse models. The COVID-19 pandemic introduced additional delays. “Disruptions caused by COVID-19, in particular the safety and tumorigenicity studies, delayed the timeline,” Thompson explained.
Another major undertaking involved creating the clinical infrastructure necessary for a first-of-its-kind procedure. Thompson said that it’s not really a challenge, but getting the overall procedural pipeline in place is the first study of this kind at the UCI Health–Irvine hospital in the MRI suite.
Despite the complexity of the project, Thompson said interactions with regulators proceeded smoothly. “We actually had a very good experience in terms of regulatory activities. A very helpful pre-pre-IND, pre-IND and relevant feedback from the FDA on the clinical trial.”
Scalability and competitive landscape
Whether hNSC-01 will ultimately compete with or complement emerging gene-targeting therapies remains unclear. Gene-silencing approaches may be easier to distribute because they do not require brain surgery, but repeated administrations over many years could result in substantial cumulative costs. In contrast, hNSC-01 involves a specialized MRI-guided neurosurgical procedure that may initially be limited to major medical centers, but it is designed as a one-time treatment whose long-term costs could compare favorably with chronic therapies if benefits prove durable.
Thompson believes the infrastructure requirements may be less of a barrier than many assume. “Yes, major medical centers can eventually offer it, and several medical centers are now using this system for other indications,” she said. “The other aspect is this would be a one-time administration so an individual could even travel to a medical center that offers the procedure.”
The REGEN4HD trial plans to enroll 21 adults aged 18 to 65 with early-stage Huntington’s disease. Twelve participants will be included in a Phase Ib dose-escalation cohort, while nine additional participants will be enrolled in a Phase IIa expansion group. The study is funded through a $12 million grant from the California Institute for Regenerative Medicine and coordinated through the UC Irvine Alpha Clinic, one of nine state-supported regenerative medicine clinical research centers.
Even if the therapy proves safe and beneficial, researchers caution that it remains unclear whether stem cell transplantation alone will be sufficient to combat Huntington’s disease over the long term. “At this point we do not know whether this will be sufficient alone or will need to be delivered with other disease-modifying therapies,” said Thompson. “For example, ones that specifically target an HD mechanism such as somatic repeat instability,” Thompson said. “However, these cells also have the potential to exert therapeutic effects directly while serving as vehicles for the delivery of additional interventions.”
For families affected by Huntington’s disease, the first successful treatment in the REGEN4HD trial represents more than a scientific milestone. It marks the beginning of a new chapter in regenerative medicine—one that researchers hope could eventually transform the outlook for a disease that has long remained untreatable.
The post First Huntington’s Disease Patient Dosed with Neural Stem Cell Therapy appeared first on Inside Precision Medicine.
Angry Kids: Dealing With Explosive Behavior
When a child — even a small child — melts down and becomes aggressive, they can pose a serious risk to themselves and others, including parents and siblings.
It’s not uncommon for kids who have trouble handling their emotions to lose control and direct their distress at a caregiver — screaming and cursing, throwing dangerous objects, or hitting and biting. It can be a scary, stressful experience for you and your child, too. Children often feel sorry after they’ve worn themselves out and calmed down.
So what are you to do?
It’s helpful to first understand that behavior is communication. A child who is so overwhelmed that they are lashing out is a distressed child. They don’t have the skill to manage their feelings and express them in a more mature way. They may lack language, impulse control, or problem-solving abilities.
Sometimes parents see this kind of explosive behavior as manipulative. But kids who lash out are usually unable to handle frustration or anger in a more effective way — say, by talking and figuring out how to achieve what they want.
Nonetheless, how you react when a child lashes out has an effect on whether they will continue to respond to distress in the same way or learn better ways to handle feelings so they don’t become overwhelming.
Behavioral techniques for anger management
Here are some pointers to help kids learn techniques to regulate their emotions:
- Stay calm. Faced with a raging child, it’s easy to feel out of control and find yourself yelling at them. But when you shout, you have less chance of reaching them. Instead, you will only be making them more aggressive and defiant. As hard as it may be, if you can stay calm and in control of your own emotions, you can be a model for your child and teach them to do the same thing.
- Don’t give in. Don’t encourage them to continue this behavior by agreeing to what they want in order to make it stop.
- Praise appropriate behavior. When they have calmed down, praise them for pulling themselves together. And when they do try to express their feelings verbally, calmly, or try to find a compromise on an area of disagreement, praise them for those efforts.
- Help them practice problem-solving skills. When your child is not upset is the time to help them try out communicating their feelings and coming up with solutions to conflicts before they escalate into aggressive outbursts. You can ask them how they feel and how they think you might solve a problem.
- Time-outs and reward systems. Time-outs for nonviolent misbehavior can work well with children younger than 7 or 8 years old. When using time-outs, be sure to be consistent with them and balance them with other, more positive forms of attention. If a child is too old for time-outs, you want to move to a system of positive reinforcement for appropriate behavior — points or tokens toward something they want.
- Avoid triggers. Vasco Lopes, PsyD, a clinical psychologist, says most kids who have frequent meltdowns do it at very predictable times, like homework time, bedtime, or when it’s time to stop playing, whether it’s Legos or video games. The trigger is usually being asked to do something they don’t like, or to stop doing something they do like. Time warnings (“we’re going in 10 minutes”), breaking tasks down into one-step directions (“first, put on your shoes”), and preparing your child for situations (“please ask to be excused before you leave Grandma’s table”) can all help avoid meltdowns.
What kind of tantrum is it?
How you respond to a tantrum also depends on its severity. The first rule in handling nonviolent tantrums is to ignore them as often as possible, since even negative attention, like telling the child to stop, can be encouraging.
But when a child is getting physical, ignoring is not recommended since it can result in harm to others as well as your child. In this situation, Dr. Lopes advises putting the child in a safe environment that does not give them access to you or any other potential rewards.
Critics of time-outs argue that they can be emotionally isolating for kids, but research shows that they are effective and do not cause children harm. (For more on the debate around time-outs, read our full article on the topic.) However, it’s very important to use them as just one technique in a nurturing, supportive parenting strategy. Be sure to balance use of time outs with lots of praise for kids’ positive behaviors. It’s also important to manage your own stress so that kids can learn how to regulate their emotions from your positive example.
If the child is young (usually 7 or younger), try placing them in a time out chair. If they won’t stay in the chair, take them to a backup area where they can calm down on their own without anyone else in the room. Again, for this approach to work there shouldn’t be any toys or games in the area that might make it rewarding.
Your child should stay in that room for one minute and must be calm before they are allowed out. Then they should come back to the chair for time out. “What this does is gives your child an immediate and consistent consequence for their aggression and it removes all access to reinforcing things in their environment,” explains Dr. Lopes.
If you have an older child who is being aggressive and you aren’t able to carry them into an isolated area to calm down, Dr. Lopes advises removing yourself from their vicinity. This ensures that they are not getting any attention or reinforcement from you and keeps you safe. In extreme instances, it may be necessary to call 911 to ensure your and your child’s safety.
Help with behavioral techniques
If your child is doing a lot of lashing out — enough that it is frequently frightening you and disrupting your family — it’s important to get some professional help. There are good behavioral therapies that can help you and your child get past the aggression, relieve your stress, and improve your relationship. You can learn techniques for managing their behavior more effectively, and they can learn to rein in disruptive behavior and enjoy a much more positive relationship with you.
- Parent-child interaction therapy (PCIT). PCIT has been shown to be very helpful for children between the ages of 2 and 7. The parent and child work together through a set of exercises while a therapist coaches parents through an ear piece. You learn how to pay more attention to your child’s positive behavior, ignore minor misbehaviors, and provide consistent consequences for negative and aggressive behavior, all while remaining calm.
- Parent management training (PMT). PMT teaches similar techniques as PCIT, though the therapist usually works with parents, not the child.
- Collaborative and Proactive Solutions (CPS). CPS is a program based on the idea that explosive or disruptive behavior is the result of lagging skills rather than, say, an attempt to get attention or test limits. The idea is to teach children the skills they lack to respond to a situation in a more effective way than throwing a tantrum.
Figuring out explosive behavior
Tantrums and meltdowns are especially concerning when they occur more often, more intensely, or past the age in which they’re developmentally expected — those terrible twos up through preschool. As a child gets older, aggression becomes more and more dangerous to you, and the child. And it can become a big problem for them at school and with friends, too.
If your child has a pattern of lashing out it may be because of an underlying problem that needs treatment. Some possible reasons for aggressive behavior include:
- ADHD: Kids with ADHD are frustrated easily, especially in certain situations, such as when they’re supposed to do homework or go to bed.
- Anxiety: An anxious child may keep their worries secret, then lash out when the demands at school or at home put pressure on them that they can’t handle. Often, a child who “keeps it together” at school loses it with one or both parents.
- Undiagnosed learning disability: When your child acts out repeatedly in school or during homework time, it could be because the work is very hard for them.
- Sensory processing issues: Some children have trouble processing the information they are taking in through their senses. Things like too much noise, crowds and even “scratchy” clothes can make them anxious, uncomfortable, or overwhelmed. That can lead to actions that leave you mystified, including aggression.
- Autism: Children with autism spectrum disorder are often prone to meltdowns when they are frustrated or faced with unexpected change. They also often have sensory issues that make them anxious and agitated.
Given that there are so many possible causes for emotional outbursts and aggression, an accurate diagnosis is key to getting the help you need. You may want to start with your pediatrician. They can rule out medical causes and then refer you to a specialist. A trained, experienced child psychologist or psychiatrist can help determine what, if any, underlying issues are present.
When behavioral plans aren’t enough
Professionals agree, the younger you can treat a child, the better. But what about older children and even younger kids who are so dangerous to themselves and others that behavioral techniques aren’t enough to keep them and others around them safe?
- Medication. Medication for underlying conditions such as ADHD and anxiety may make your child more reachable and teachable. Kids with extreme behavior problems are often treated with antipsychotic medications like Risperdal or Abilify. But these medications should be partnered with behavioral techniques.
- Holds. Parent training may, in fact, include learning how to use safe holds on your child so that you can keep both them and yourself out of harm’s way.
- Residential settings. Children with extreme behaviors may need to spend time in a residential treatment facility — sometimes, but not always, in a hospital setting. There, they receive behavioral and, most likely, pharmaceutical treatment. Therapeutic boarding schools provide consistency and structure around the clock, seven days a week. The goal is for the child to internalize self-control so they can come back home with more appropriate behavior with you and the world at large.
- Day treatment. With day treatment, a child with extreme behavioral problems lives at home but attends a school with a strict behavioral plan. Such schools should have trained staff prepared to safely handle crisis situations.
Explosive children need calm, confident parents
It can be challenging work for parents to learn how to handle an aggressive child with behavioral approaches, but for many kids it can make a big difference. Parents who are confident, calm, and consistent can be very successful in helping children develop the anger management skills they need to regulate their own behavior.
This may require more patience and willingness to try different techniques than you might with a typically developing child, but when the result is a better relationship and happier home, it’s well worth the effort.
Frequently Asked Questions
One way to handle a child’s anger is to stay calm when they lose their temper. Controlling your emotions sets an example for the child. You can praise them when they express their feelings calmly and when they calm themselves down after an explosion. Adults who are confident, calm, and consistent help children develop the skills to regulate their behavior.
In parent-child interaction therapy, a therapist coaches parents on how to pay more attention to positive behavior, ignore minor misbehaviors, and provide consistent consequences for negative and aggressive behavior, all while remaining calm. Other forms of therapy also center on teaching the parent how to model emotional stability.
Stay calm and ensure they are in a safe space. Yelling can escalate aggression. Speak in a steady voice, avoid giving in, and use time-outs to prevent meltdowns. When they calm down, praise them for it and for expressing their emotions appropriately. If they are frequently aggressive, behavioral therapy may help.
Children who lash out often lack the skills to manage emotions. Identifying triggers, teaching problem-solving, and using praise or rewards can encourage better behavior. Time-outs work for younger kids, while older ones may need structured reinforcement. If outbursts are severe, you might need professional help. Programs like parent-child interaction therapy (PCIT), parent management training (PMT), or collaborative and practical solutions (CPS) can help.
The post Angry Kids: Dealing With Explosive Behavior appeared first on Child Mind Institute.
First-in-Human Stem Cell Therapy Trial for Huntington’s Disease Begins at UCI Health
The world’s first in-human embryonic stem cell-derived clinical trial for Huntington’s disease has launched at UCI Health, the clinical arm of the University of California, Irvine. The Phase Ib/IIa trial will evaluate the safety of hNSC-01 neural stem cells derived from embryonic stem cells delivered to the brain by a specialized neurological mapping and targeting stereotactic system.
Huntington’s disease is a fatal, progressive genetic disorder that gradually destroys brain cells. It usually begins between the ages of 35 and 50 with symptoms that include involuntary movements, difficulty thinking and planning daily tasks, and mood changes such as depression. If successful, this therapy could prolong independent living and significantly reduce long-term care costs.
“This clinical trial highlights the important role that an interdisciplinary academic and clinical team together with the HD families, plays in advancing medicine,” said Leslie M. Thompson, PhD, professor of psychiatry and human behavior at UC Irvine. “We are grateful to our patients and their incredible families for their bravery to provide hope for others with very few options.”
The first patient received the intervention at UCI Health Irvine (home to Orange County’s first adult bone marrow/stem cell transplant and cellular therapy program) in May. A second patient is scheduled to receive the intervention in July.
“The first patient intervention went very well. To date, they haven’t reported any serious adverse events,” said Ravi Rajmohan, MD, UCI Health neurologist. “This trial may help us move one step closer to a future with available treatments that could potentially slow the progression of Huntington’s disease.”
The therapy, hNSC-01, uses pluripotent neural stem cells derived from embryonic stem cells, which were manufactured through the UC Davis GMP facility. In animal studies, the cells have been shown to protect existing brain cells, replace lost cells, rebuild impaired brain circuits, release helpful proteins, such as brain-derived neurotrophic factor (BDNF), and reduce harmful protein accumulations that damage brain cells. The stem cells were also shown to be safe over long periods in mice.
The clinical trial will enroll 21 people ages 18 to 65 with early-stage Huntington’s disease. Twelve participants will be enrolled into a Phase Ib dose-escalation group and nine in a Phase IIa expansion group.
The stem cells are implanted during a roughly six-hour surgical procedure done under general anesthesia. While lying face down in an MRI scanner, the patient receives stem cells implanted directly into the striatum deep in the brain, using a purchased proprietary therapy-enabling platform for navigation and surgical delivery. Damage to the striatum, which is responsible for motor control, decision-making, motivation and more, causes Huntington’s disease symptoms. Subjects will be closely monitored for safety as well as preliminary signs of potential benefit.
The clinical trial is made possible by a $12 million grant from the California Institute of Regenerative Medicine (CIRM), and the trial is coordinated through the UC Irvine Alpha Clinic.
The post First-in-Human Stem Cell Therapy Trial for Huntington’s Disease Begins at UCI Health appeared first on GEN – Genetic Engineering and Biotechnology News.
TIC-XNet: a structured evidence translation framework for interpretable multimodal pediatric tic event detection with improved temporal alignment and fidelity
ObjectivesThis study aimed to develop an interpretable multimodal framework for detecting tic events in children with tic disorders by translating model decisions into structured, time-aligned evidence from synchronized video and physiological signals.MethodsTIC-XNet was developed to jointly analyze synchronized video, heart rate, and electrodermal activity signals and to generate structured evidence outputs. Recordings from 417 children with clinically diagnosed tic disorders were collected during structured clinical assessments and home-based observations. TIC-XNet was compared with a prediction-only black-box model and a post-hoc explainable model under matched predictive backbones and identical training settings.ResultsWithin the evaluated internal subject-level split, TIC-XNet achieved the best performance on the pooled shared test set, with a window-level AUC of 0.915 ± 0.019, higher event-level recall and precision, fewer missed events, and lower post-buffering prediction latency than the comparator models. Its translated outputs also showed higher decision fidelity, greater stability under perturbation, and closer temporal alignment with expert-annotated tic onsets. Subject-level translated numerical signals were associated with tic severity.ConclusionsThese findings indicate that evidence translation can support more interpretable multimodal detection of tic events in children with tic disorders while remaining compatible with strong predictive performance.
Deep and repetitive transcranial magnetic stimulation improves motor dysfunction after basal ganglia infarction: preliminary findings on efficacy and electrophysiological mechanisms
ObjectiveTo observe the therapeutic effects of deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) on upper and lower limb motor dysfunction in patients with basal ganglia infarction, and to preliminarily explore their underlying electrophysiological mechanisms.MethodsThirty patients with motor dysfunction secondary to basal ganglia infarction, hospitalized at the Affiliated Hospital of North Sichuan Medical College between October 2024 and December 2025, were enrolled in this study. All eligible participants were randomly assigned to one of three treatment groups: dTMS (n = 10), rTMS (n = 10), or sham stimulation (n = 10). All patients in the three groups received routine medical treatment and conventional rehabilitation training. On this basis, the dTMS group was treated with 10 Hz dTMS, the rTMS group with 10 Hz rTMS, and the sham stimulation group with sham stimulation, 5 sessions per week for 2 consecutive weeks. Before treatment, on the first day after treatment, and at 30 days after treatment, the Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), and Modified Barthel Index (MBI) were used to evaluate motor function of the affected side and activities of daily living. The resting motor threshold (rMT) and central motor conduction time (CMCT) of the affected hemisphere were measured simultaneously.ResultsThe baseline data among the three groups were comparable (all p > 0.05); After treatment, there was a statistically significant interaction between group and time in FMA-UE, FMA-LE, MBI, and BBS scores among the three groups (all p < 0.05); Compared with baseline, FMA-UE, FMA-LE, MBI, and BBS scores were significantly increased on the first day and at 30 days after treatment in all three groups (all p < 0.001); Compared with the sham stimulation group, the dTMS group exhibited higher FMA-UE, FMA-LE, MBI, and BBS scores on the first day and at 30 days after treatment (all p < 0.05); Compared with the rTMS group, the dTMS group showed no significant differences in FMA-UE and MBI scores on the first day after treatment (all p > 0.05), but higher FMA-LE and BBS scores (all p < 0.05), at 30 days after treatment, FMA-UE, FMA-LE, MBI, and BBS scores were all higher in the dTMS group (all p < 0.05). There was a statistically significant interaction between group and time in rMT and upper limb CMCT among the three groups after treatment (all p < 0.05); Compared with baseline, rMT and upper limb CMCT were significantly decreased on the first day and at 30 days after treatment in all three groups (all p < 0.001); Compared with the sham stimulation group, the dTMS group had lower rMT and upper limb CMCT on the first day and at 30 days after treatment (all p < 0.05); Compared with the rTMS group, the dTMS group showed lower rMT and upper limb CMCT on the first day after treatment (p < 0.05), at 30 days after treatment, rMT was lower (p < 0.05), while no significant difference was found in upper limb CMCT (p > 0.05).Conclusion(1) Both high-frequency dTMS and rTMS can improve upper limb motor dysfunction after basal ganglia cerebral infarction to some extent, and the therapeutic effect of dTMS lasts longer; (2) dTMS has a certain rehabilitative effect on lower limb motor and balance function; (3) The mechanisms underlying the improvement of motor dysfunction after basal ganglia cerebral infarction by high-frequency dTMS and rTMS may be associated with increased excitability of the affected cerebral cortex, enhanced function of the corticospinal tract pathway. In addition, dTMS can directly act on deeper and wider brain regions; (4) Both high-frequency dTMS and rTMS are safe.
Cerebellar aging is spatially heterogeneous and supports cognitive resilience in later life
Nature Neuroscience, Published online: 10 June 2026; doi:10.1038/s41593-026-02289-x
The cerebellum ages unevenly, with some regions showing preservation that may help protect the brain from decline. The authors show that large cerebellar volume is associated with stronger cognitive resilience in healthy aging and Alzheimer’s disease.