BackgroundAdolescent depression exhibits distinct neurophysiological features, with marked age heterogeneity particularly in the resting motor threshold (RMT) measured during repetitive transcranial magnetic stimulation (rTMS), and substantial variability in clinical therapeutic efficacy. Functional near-infrared spectroscopy (fNIRS) enables the assessment of cortical excitability levels; however, research investigating the association between RMT and cortical activation in adolescent patients with depression remains limited. This study aims to elucidate the underlying neural mechanisms from the perspective of cortical hemodynamics, which is crucial for further optimizing neuromodulation strategies in patients with depression.MethodsWe collected data from 85 treatment-naive patients with depression who underwent rTMS therapy. All patients completed RMT measurement, fNIRS examination, and Hamilton Depression Rating Scale (HAMD) assessment prior to rTMS treatment. Participants were divided into three groups according to age: the adolescents group (n=31), the young adult group (n=26), and the middle-aged group (n=28). We compared the differences in RMT among the three groups and explored the relationships between RMT, cortical activation (reflected by prefrontal oxyhemoglobin level changes during the verbal fluency task via fNIRS), and depression severity (assessed by HAMD scores).ResultsThe results demonstrated that the adolescents group had a significantly higher RMT than the other age groups (58.00 ± 11.14, P < 0.001), accompanied by the lowest prefrontal Oxy-Hb activation level (0.095 ± 0.06, P < 0.001). A strong negative correlation was observed between RMT and cortical activation (Spearman’s rs= -0.929, P < 0.001), while a strong positive correlation was found between RMT and depression severity (Spearman’s rs = 0.837, P < 0.001). The distinct coupling phenomenon of high threshold-low activation-severe symptoms was most prominently manifested in this age group, which may theoretically reflect an underlying dysregulation in broader emotional networks, though the current direct findings strictly indicate localized alterations in prefrontal activation and motor cortical excitability.ConclusionsThe characteristics of high RMT and low cortical activation in adolescent depression serve as important neurobiological markers for depression severity. This finding provides a novel direction for developing individualized, developmentally tailored neuromodulation strategies (e.g., optimization of rTMS targets and dosages), indicating that interventions for adolescent depression should prioritize promoting the healthy integration of emotional circuits and the functional coordination between the cortex and subcortex.
Advancing conversational diagnostic AI with multimodal reasoning
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04371-0
Improvements in the Articulate Medical Intelligence Explorer, a large language model designed for diagnostic dialogue, enable the model to request, interpret and reason about multimodal medical data.
Performance of traumatic encephalopathy syndrome criteria in identifying individuals with chronic traumatic encephalopathy
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04392-9
The proposed clinical features of traumatic encephalopathy syndrome have low predictive value for chronic traumatic encephalopathy pathology, raising significant concern for incorrect diagnoses of neurodegeneration in former athletes.
Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial
Nature Medicine, Published online: 14 May 2026; doi:10.1038/s41591-026-04395-6
Subcutaneous injections of abatacept were superior to oral hydroxychloroquine in preventing progression to persistent arthritis in individuals with palindromic rheumatism.
Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming
Nature Neuroscience, Published online: 14 May 2026; doi:10.1038/s41593-026-02300-5
This study reveals that the immune system has a role in driving ALS. These findings link blood immune changes to spinal cord damage and suggest personalized treatments targeting specific immune pathways.
Synchronous climbing fiber activity enables instructive signaling for cerebellar learning through modulation of disinhibitory circuits
Nature Neuroscience, Published online: 14 May 2026; doi:10.1038/s41593-026-02268-2
Combining connectomics, physiology and behavior, this study shows how the cerebellum decides when to learn. Synchronized climbing-fiber error signals lift an inhibitory signal gate on Purkinje cells, enabling synaptic plasticity and motor adaptation.
STAT+: Three years of declining overdose deaths begets cautious optimism and some concerns
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The Trump admin’s wish list for its next FDA leader
The Trump administration is working to identify the next FDA commissioner after Marty Makary resigned on Tuesday. The dream candidate is someone who can rebuild trust with agency staff, focus on the agency’s food policy, and continue to drive drug-approval reforms, STAT’s Daniel Payne and Lizzy Lawrence report.
STAT+: Biogen’s tau-targeting Alzheimer’s drug posts mixed results in mid-stage study
Biogen reported mixed results Thursday from a mid-stage clinical trial investigating a treatment for Alzheimer’s disease that targets the protein tau that, like the better-known amyloid, is toxic to neurons and is believed to play a role in the cognitive decline of patients with the disease.
In the Phase 2 study, the Biogen drug, called diranersen, or BIIB080, reduced levels of tau in the spinal fluid and brains of patients with early-stage Alzheimer’s. Those tau reductions also correlated to a slowing of cognitive decline, the company said.
Biogen investigated three escalating dosing regimens in its study, with the lowest dose showing the best results. For that reason, the study failed to achieve its primary efficacy goal, which was a dose response.
STAT+: CREATE Medicines, a biotech company developing CAR-T therapies, raises $122 million
CREATE Medicines has a new name, an expanded pipeline, and now fresh funding to propel the company’s first CAR-T candidates through human trials.
Up until last year, CREATE was known as Myeloid Therapeutics. The startup was cofounded by noted writer and oncologist Siddhartha Mukherjee to develop better CAR-T therapies using a type of immune agent called myeloid cells, ideally to better attack solid tumors. The company rebranded last fall and, like many other oncology CAR-T companies, expanded into autoimmune disease research.
Now, CREATE has raised another $122 million from Newpath Partners, ARCH Venture Partners, Hatteras Venture Partners, and others, the biotech told STAT exclusively.
STAT+: Regenxbio says Duchenne gene therapy succeeded in clinical trial, paving way for FDA submission
Regenxbio said Thursday that its experimental gene therapy for Duchenne muscular dystrophy produced sufficiently high levels of a miniaturized muscle protein broken in the fatal neuromuscular disease, paving the way for a submission to the Food and Drug Administration.
The company is seeking to create a Duchenne gene therapy that is more effective and safer than Sarepta Therapeutics’ Elevidys, which has been hampered by safety concerns, particularly following the deaths of two recipients from liver failure.
“I think our data checks every single box that you would want for accelerated approval,” Regenxbio CEO Curran Simpson told STAT.