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.
Complete Connectome of Fruit Fly Central Nervous System Now Open-Source
A new study published in Nature titled, “Distributed control circuits across a brain-and-cord connectome”, describes a complete wiring diagram of all the connections between neurons in the central nervous system of an adult fruit fly for translational applications.
The work was completed by an international team led by multiple labs at Harvard Medical School (HMS) and Princeton University. The team has made the entire connectome accessible online to propel research into complex behaviors and other fundamentals of the nervous system.
The fruit fly, Drosophila melanogaster, offers an effective model as they are easy to breed and maintain in the lab. Despite having a relatively simple nervous system made up of around 160,000 neurons, they exhibit complex behaviors such as navigation, social interaction, learning, and responding to sensory cues.
To build the connectome, the team used electron microscopy to produce millions of images of neurons and neural connections. AI tools aligned the images into a cohesive 3D map.
“It is really important to have a central nervous system connectome that is as complete as possible so we can link up the brain and body and start thinking about behavior holistically,” said Wei-Chung Allen Lee, PhD, associate professor of neurobiology at HMS and co-corresponding author on the study.
The connectome shows how each neuron connects in the brain and nerve cord at the synapse level. While the map doesn’t span the fly’s entire body, the team used identifiable neurons and literature review to connect the central nervous system to neurons in appendages and sensory organs.
The authors have already used the connectome to explore motor control. While a longstanding idea in neuroscience is for a centralized controller in the brain to make decisions about actions, the authors discovered that motor control in the fruit fly mostly occurs at a local level. For example, movement of a fly’s leg is primarily controlled by the neural circuits for that leg. The local circuits for one leg then communicates with other appendages to carry out complex coordinated movements, such as walking.
“The brain and nerve cord connectomes are each useful on their own, but until you can bridge the two, it’s hard to understand how information moves between the brain and the body,” said co-first author Helen Yang, PhD, a research fellow in neurobiology at HMS.
Looking ahead, the researchers plan to add more information to the connectome, including data describing neuropeptides, molecules that support neuron communication. Insights from the connectome may reveal fundamental principles about how nervous systems operate across species, including in humans.
The post Complete Connectome of Fruit Fly Central Nervous System Now Open-Source appeared first on GEN – Genetic Engineering and Biotechnology News.
<![CDATA[Expert analysis compares adjunctive atypical antipsychotics for MDD, highlighting lumatperone’s larger effect and minimal weight gain or akathisia.]]>
Tics and OCD: Why Treatments Differ and Ways to Support Your Kids
by Dr. Christine Conelea and Dr. Adrienne Manbeck
Tics, compulsions, and obsessions are part of many people’s everyday lives. As clinicians and researchers at the University of Minnesota Tic and Compulsivity Lab (MnTiC), we see people living with different, unique combinations of these symptoms that can feel interconnected. There are some broad differences between tics, obsessions, and compulsions, but it’s important to note that they do overlap and that a person can have all of these things at the same time. Still, disentangling symptoms in order to provide effective treatment can sometimes be challenging.
Tics and compulsions are similar in that they both involve movements that are repetitive and difficult for the person to control. Research has shown that overlapping genetic, neurological, and psychological factors contribute to both experiences. Because of this, researchers and clinicians consider both tics and compulsions to be on the “obsessive-compulsive spectrum.” However, there are important differences in treatment and in how loved ones can provide support.
Behaviors
Tics are sudden, repetitive, involuntary movements or sounds that are usually very brief. Common tics include rapid or hard eye blinking, facial scrunching, throat clearing or sniffing. In our studies, we have found that people with tics have an average of 8 tics per minute.
Many individuals with tics experience an urge right before they tic. This urge can feel like tension, an itch or pressure that typically goes away after the tic occurs. Tics tend to wax and wane over time. Compulsions are often more rule bound or rigid and are driven by a thought. Common compulsions include checking, counting, washing and reordering. They tend to be longer, smooth movements or sequences of movements. They’re linked to very specific situations, triggers, or thoughts to prevent something bad from happening or to relieve anxiety.
Why Treatments Differ
Although tic disorders and OCD sometimes look similar on the surface (repetitive movements can occur in both), they are different disorders. Subjectively speaking, tics can feel like a “body itch” while compulsions might feel like a “brain itch.” Though they may be very connected for some people, what works for one won’t necessarily work for the other.
In general, we often take a less interventionist approach to tic disorders because tics may not be inherently harmful. On the other hand, because compulsions work to reinforce obsessive thoughts and provide escape from non-harmful but unpleasant feelings, we often intervene with OCD as soon as possible. As clinicians working with children and teens, we want to help kids learn to be brave, learn that they can tolerate distress associated with anxiety, and learn that OCD doesn’t get to make their decisions for them.
Watchful Waiting
In general, OCD will not get better on its own. If a parent notices symptoms associated with distress or impairment, taking action of some kind is often the best approach. If tics aren’t causing problems for a child, it might be best to monitor. If tics become painful, start to bother your child, or in some other way cause harm, that might be the time to pursue treatment. The American Academy of Neurology refers to this as “watchful waiting” and sees it as an appropriate treatment, in some cases, for tics.
Tips for Providing Support
People with tic disorders face high stigma and discrimination compared to the general population. Tics are often hyper-visible and poorly understood. For OCD, stigma is more likely to emerge from public messaging rather than hypervisibility. The general public talks about OCD in a highly stereotyped way that misses a lot of people’s actual experiences with OCD and can trivialize symptoms.
For both OCD and tic disorders, parents can help support their child by collaboratively developing a reward structure for hard work in therapy.
For tic disorders, research has shown that situational factors have an important role in influencing tics, including what a person is doing, who is around them, and how they are feeling. Most people can identify situational factors that make their tics better or worse. Some factors frequently associated with tic exacerbation are fatigue, social events, and starting school in the fall. Stress, frustration, or anxiety-provoking events can make it harder for the brain to inhibit tics. Events frequently reported to coincide with tic reductions include social interactions with familiar people, situations in which the individual is a passive participant or deeply focused on a task, and leisure activities.
Because tics are so reactive to situational factors, one of the best ways to provide support is to create tic-neutral environments. This means eliminating intended or unintended consequences related to the tics, such as minimizing reactions to tics or changes to activities because of tics. We frame this as, “focusing on the person instead of the tics.” Tic neutrality can also help children feel better about tics since they can’t control them.
For OCD, minimizing parent accommodation, parents helping kids avoid anxiety-provoking things, can be helpful. Parents can help their kids by reducing accomodation and encouraging their children to be brave and face their fears in manageable, developmentally-appropriate ways.
About the Authors:
Christine Conelea, PhD is an Associate Professor in the Department of Psychiatry & Behavioral Sciences at the University of Minnesota, a licensed clinical psychologist, and the director of the MnTiC Lab. Dr. Conelea’s research interests include Tourette Syndrome/tic disorders, obsessive-compulsive disorder (OCD), and anxiety disorders. She is particularly interested in understanding how the brain, environment, and psychosocial factors interact to impact symptoms and treatment outcomes.
Adrienne Manbeck, PhD, is a postdoctoral fellow in the MnTiC Lab. Dr. Manbeck earned her doctorate in clinical psychology at the University of Minnesota and completed her pre-doctoral internship at Allegheny General Hospital in Pittsburgh, PA. Dr. Manbeck’s research aims to better understand the development, maintenance, and treatment of OCD and anxiety disorders across the lifespan, with a particular emphasis on the impact of societal stressors on these disorders, including the ways in which societal stressors impact symptom severity, access to high-quality treatment, and impact of treatment on symptoms.
More Reading:
Micali, N., Heyman, I., Perez, M., Hilton, K., Nakatani, E., Turner, C., & Mataix-Cols, D. (2010). Long-term outcomes of obsessive–compulsive disorder: Follow-up of 142 children and adolescents. British Journal of Psychiatry, 197(2), 128–134.
Conelea, C.A., Woods, D.W., Zinner, S.H. et al. The Impact of Tourette Syndrome in Adults: Results from the Tourette Syndrome Impact Survey. Community Ment Health J 49, 110–120 (2013).
Tourette Association of America Tourette Awareness Month resources
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AI-Powered Blood Test Detects Early Retinal Damage in Diabetes
Scientists have developed an AI-assisted prediction tool that can identify patients with type 2 diabetes at high risk of developing diabetic retinal neurodegeneration (DRN) before symptoms appear. Their findings were published today in the journal PLOS Medicine.
“Our study suggests that early retinal nerve damage in diabetes leaves measurable signals in the blood,” write the authors of the study, led by Wei Wang, MD, PhD, associate professor at the Guangdong Provincial Clinical Research Center for Ocular Diseases. “These findings suggest that a simple blood test analyzed with artificial intelligence may help identify people with diabetes who are at highest risk of early retinal nerve damage, well before visible damage appears on the retina.”
Type 2 diabetes affects more than half a billion people worldwide, carrying with it an increased risk of long-term complications including progressive neurodegeneration. Retinal nerves are among the earliest tissues to be damaged, which can eventually lead to severe visual impairment and vision loss. However, current diagnostic methods can only detect DRN once the retina has already suffered irreversible damage.
Wang and colleagues developed a machine learning algorithm called Pro-DRN using data from 1,218 participants in the Guangzhou Diabetic Eye Study, all of whom were diagnosed with type 2 diabetes but had not yet developed DRN at the time of enrollment. The AI model integrated proteomics data from blood samples with yearly retinal images collected over a six-year follow-up period.
This led to the identification of 71 proteins associated with the development of DRN. Among them, the proteins most consistently driving accurate predictions were ACTA2, COL6A3, and HSPG2, which are key structural components involved in maintaining the integrity of the nerve and muscle tissue in the eyes. These results were then validated in an independent cohort of 502 patients from UK Biobank, where the core effects and protein signals were reproduced.
Pro-DRN has been deployed as an interactive, web-based risk assessment tool that doctors can use to support early DRN screening and monitor patient evolution over time. Individuals identified as being at high risk of DRN could benefit from more frequent checkups and early interventions aimed at preventing or slowing down progressive neurodegeneration.
Because DRN is one of the first symptoms of nerve degeneration induced by diabetes, early detection could also signal the onset of nerve injury elsewhere in the body. Such damage can contribute to cognitive impairment, dementia, and peripheral neuropathy, which can cause loss of sensation and motor control in the hands, feet, and other extremities. A single eye test could therefore provide valuable insights into the overall health of the nervous system.
In addition, the proteins identified to be involved in DRN progression could be investigated as potential targets for the development of novel therapies. Furthermore, the AI-based tool could also prove valuable for the selection and stratification of participants in clinical trials evaluating neuroprotective strategies designed to prevent or delay nerve damage.
“Pro-DRN may help move diabetic eye care from detecting established damage toward earlier, molecularly informed risk stratification, so that closer monitoring and future neuroprotective interventions can be directed to the people most likely to benefit,” Wang and colleagues write.
The post AI-Powered Blood Test Detects Early Retinal Damage in Diabetes appeared first on Inside Precision Medicine.
Neuronal Protein Tracing Reveals How the Brain Routes Its Waste
The brain is one of the busiest organs in the body, constantly processing and reshaping itself. That activity produces an equally constant stream of molecular byproducts—proteins that need to be moved out before they accumulate. When those clearance routes slow or break down, waste lingers, and the consequences can be profound. In Alzheimer’s disease, for example, toxic proteins build up in vulnerable regions. Yet despite decades of research, scientists have lacked a clear view of how waste normally leaves the brain.
A new study from the Gladstone Institutes offers the clearest picture yet of how the brain normally takes out its trash—and what happens when those routes fail. Published in Cell as “Physiological brain clearance architecture revealed by neuronal protein tracing,” the work introduces a method that traces waste proteins from the moment they are produced inside neurons to the moment they leave the brain.
For decades, researchers have relied on injecting tracers into the cerebrospinal fluid (CSF) to visualize drainage. But this approach, while illuminating, shows all possible routes, instead of pinpointing the most-used exit. “These injected tracers disturb the very system we’re attempting to measure,” said lead author Andrew Yang, PhD, a Gladstone investigator. “We wanted to find a better way.”
Yang’s team engineered neurons in mice to produce a fluorescent protein, ZsGreen, that could be followed as it exited the brain through its natural routes. This allowed the researchers to track waste as it moved into the dura, skull, nasal cavity, and lymph nodes—regions populated by specialized immune cells that interact with brain‑derived proteins.
The resulting map diverged sharply from the field’s long‑held assumptions. Traditional CSF tracers had pointed to the cervical lymph nodes as a major drainage site. But the new method revealed that very little neuronal waste actually reaches those nodes. “We were surprised to find that very little ZsGreen drained to the cervical lymph nodes,” Yang said. “Instead, waste drained through the dura, skull, and nasal cavity. Our findings underscore why tracking waste proteins themselves, rather than movement of the cerebrospinal fluid, provides a more accurate understanding of waste clearance dynamics.”
The team also uncovered a striking organizational principle: where a protein is made determines where it drains. Proteins produced in upper forebrain regions exited through upper routes, while those from deeper structures, such as the striatum, used lower pathways. The researchers call this the brain’s “nearest‑exit” model. “It’s like each brain region has a biological ZIP code system to ensure waste will be sent to the correct drainage site,” said Nalini Rao, PhD, a postdoctoral fellow. She noted that in aging or disease, these ZIP codes may become scrambled, potentially explaining why certain regions are more vulnerable to disorders like Alzheimer’s.
Disease models reinforced the system’s fragility. In mice with acute inflammation, ZsGreen leaked directly into the bloodstream, bypassing normal routes. In an Alzheimer’s model, waste became trapped inside the brain, unable to drain effectively. “Understanding how diseases disrupt brain clearance could help us design therapeutics to target the brain border compartments and enhance waste removal,” Rao said.
With their new tracing method, Yang’s group plans to probe how clearance changes across aging, sleep, and disease—and whether brain tumors exploit these pathways to evade immune detection. The architecture of brain waste disposal, once opaque, is now open for exploration.
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Synaptic alterations are preceding the axonal loss in optic atrophy of Wolfram syndrome mouse model
BackgroundWolfram syndrome is a rare autosomal recessive disorder characterized by antibody-negative early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine-vasopressin deficiency, and progressive neurodegeneration of the brainstem and cerebellum. It is caused primarily by pathogenic variants in the WFS1 gene, which encodes a transmembrane endoplasmic reticulum–resident protein involved in the unfolded protein response and cellular calcium homeostasis. Although multiple rodent models of Wolfram syndrome have been developed and shown to exhibit visual defects, some studies have reported significant vision loss prior to any detectable axonal degeneration or myelin abnormalities, and the mechanisms underlying these early visual deficits remain poorly understood.ObjectiveRecent in vitro studies have demonstrated altered synaptic contacts and aberrant neurite morphology in WFS1-deficient cerebral organoids and human iPSC-derived neurons, respectively. These findings prompted us to investigate, for the first time in vivo, whether synaptic and dendritic abnormalities occur in the retina of Wfs1 knockout mice.MethodsUsing confocal microscopy, we examined retinal and optic nerve histology in Wfs1 knockout mice at 4 and 7 months of age.ResultsOur analysis reveals progressive synaptic alterations in the inner plexiform layer, driven by early presynaptic compartment failure. These changes represent the earliest detectable phenotype associated with vision loss in this model and precede overt axonal degeneration.ConclusionThese findings identify early synaptic preservation as a promising therapeutic target for vision loss in Wolfram syndrome.
Machine learning-based morphological brain analysis in schizophrenia and unaffected siblings: a multisite study of potential risk markers
Background and hypothesisAssessing schizophrenia risk factors is crucial for developing early preventive interventions. We hypothesized that unaffected siblings, who share high genetic risk, exhibit neuroanatomical signatures similar to affected patients, potentially reflecting early pathogenic processes.Study designTo overcome single-center limitations, we analyzed 1,018 participants from five independent, public databases. Brain MRIs were standardized via voxel-based morphometry, and covariate-adjusted z-scores were calculated for regional volumes. An ensemble support vector machine (SVM) approach, incorporating multiple models to ensure robustness, was employed to extract a multidimensional brain signature, from which a schizophrenia-like score (SPS) was derived.ResultsThe ensemble SVM achieved high classification performance (AUC = 0.99861). Across all databases, patients exhibited consistent volume reductions in frontal, temporal, insular, and thalamic regions, alongside globus pallidus enlargement. Notably, unaffected siblings were 3.8 times more likely to show brain morphological similarities to patients than were healthy controls. Furthermore, we identified a novel imaging phenotype in siblings: increased ventral striatal volume, which positively correlated with the SPS. This feature, absent in established schizophrenia, suggests a potential compensatory mechanism or a transient developmental marker of risk.ConclusionApplying machine learning to large-scale, multi-site neuroimaging data effectively identifies structural endophenotypes. Our findings highlight unique structural characteristics, specifically the enlarged ventral striatum, as a critical biological metric for identifying high-risk individuals before clinical onset.
Amelioration of tic disorder by Jujuboside A via gut microbiota remodeling and intestinal 5-HT signaling
BackgroundTic disorder (TD) is a common chronic neuropsychiatric condition manifesting during childhood and adolescence. Jujuboside A (JuA) may alleviate TD symptoms; however, the mechanisms underlying its therapeutic effects remain unclear.MethodsWe established a rat model of TD and used histological techniques to evaluate the effects of JuA on pathological changes. We also measured 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels and assessed tryptophan hydroxylase 1 (TPH1) mRNA expression. Finally, we analyzed the gut microbiota composition in fecal samples using 16S rRNA metagenomic sequencing.ResultsJuA administration alleviated pathological changes in rats with TD, increased 5-HT and 5-HIAA levels, and upregulated TPH1 mRNA expression. Compared with no treatment, JuA treatment increased the proportion of Bacteroidia, Muribaculaceae, Bacteroidales, and Bacteroidota, while reducing that of Bacilli, Lactobacillaceae, Lactobacillus, Lactobacillales, and Firmicutes.ConclusionThese findings indicate that JuA mitigates TD progression, potentially by remodeling the gut microbiota and regulating 5-HT levels.