ABSTRACTThe transition from static to dynamic vision is encoded in the superior colliculus (SC), as recently shown using blood oxygen level–dependent functional magnetic resonance imaging (BOLD‐fMRI) of the rat brain. Visual stimulation at a higher frequency than the flicker fusion frequency threshold is associated with a negative BOLD response in the visual cortex, triggered by the SC. Here, we explored this mechanism in further depth using visual stimulation at low (1 Hz) and high (25 Hz) frequencies in the rat. We used both BOLD‐fMRI and apparent diffusion coefficient (ADC)–fMRI to yield complementary information on brain activity during visual stimulation, from neurovascular and neuromorphological coupling perspectives. We compared responses between different brain regions (the dorsolateral geniculate nucleus, the medial and lateral parts of the SC, the corpus callosum, and the visual cortex), sexes, and field strengths (9.4 and 14 T). Results confirmed distinct BOLD responses to low‐ and high‐frequency stimulation and highlighted for the first time that the transition from static to dynamic vision is characterized by negative BOLD in the lateral SC specifically. Whereas the BOLD response to visual stimulation depends on the vasculature properties across brain regions and sexes, we found a significant ADC‐fMRI response (in the form of reduced ADC during excitatory activity) in the SC that was more consistent across visual frequencies, as well as in the corpus callosum, to which BOLD was not sensitive. Our results support an interplay between neural activity and hemodynamic response underlying the transition from static to dynamic vision, best characterized using two fMRI contrasts.

In light-sheet fluorescence microscopy (LSFM), the axial resolution is governed by the illumination beam profile, motivating the development of advanced beam-shaping techniques to enhance imaging performance. Two-photon LSFM (2P-LSFM), in particular, improves the signal-to-background ratio by reducing laser scattering and distortion in biological specimens. However, we report a potentially detrimental thermal effect in 2P-LSFM: the high laser powers required for two-photon excitation induce localized heating, which alters the refractive index of the medium and effectively forms a divergent thermal lens in water. At 500 mW, the light-sheet waist broadens by 25% and shifts by 300 μm before stabilizing several seconds after the laser shutter is opened. Both experiments and simulations reveal that this thermal lensing effect scales with laser power and the path length the beam travels through water. The resulting degradation in resolution and signal-to-noise ratio may compromise imaging applications that require high laser powers for rapid volumetric imaging of large specimens or functional brain imaging. This limitation is particularly critical in dynamic sample environments, such as during stepwise repositioning or flow-based delivery of chemical or hydrodynamic sensory stimuli, where changes occur on timescales comparable to the thermal settling time.

ABSTRACTPreliminary animal and human studies have shown that blood dihydrotestosterone concentrations are increased in males with alcohol use disorder, and 5α‐reductase inhibitors, which decrease dihydrotestosterone concentrations, reduce alcohol consumption. To gain mechanistic insight, we studied the effects of reduced dihydrotestosterone concentrations following pharmacological 5α‐reductase inhibition on alcohol cue‐elicited brain activity and alcohol craving in males with problematic alcohol use. To this end, this randomized, placebo‐controlled, crossover challenge experiment investigated associations between dihydrotestosterone concentrations and brain functional magnetic resonance imaging (fMRI) activity during exposure to visual alcohol cues and alcohol craving following a single dose of 5 mg finasteride versus placebo in 50 males with heavy episodic drinking. We used finasteride because it specifically inhibits 5α‐reductase II activity, which is the main enzyme converting testosterone to dihydrotestosterone. Dihydrotestosterone concentrations were lower in the finasteride condition in comparison to the placebo condition, but not significantly associated with brain activation patterns or craving. In the exploratory analyses, we found higher brain activity during exposure to visual stimuli in the right and left caudate nuclei, the right superior frontal gyrus and the left insula in the finasteride condition versus the placebo condition. Moreover, finasteride versus placebo was associated with a higher wish to not drink alcohol. The results of this experimental study do not support the à priori hypothesis that dihydrotestosterone concentrations play a role in brain activation during exposure to visual alcohol cues, but indicate that finasteride effects may be mediated by other pathways. Future studies are requested to investigate the effects of reduced dihydrotestosterone concentrations over a longer time and to shed light on the molecular mechanisms underlying the here observed effects of finasteride.Trial Registration: DRKS00020569

There remain large variations in cochlear implant auditory-speech perception ability, which are poorly explained by patient history factors. This study aims to better understand how combinations of speech processing limitations, identified using psychophysical and functional brain imaging measures, are associated with long-term speech understanding outcomes of new cochlear implant recipients. Forty-three cochlear implant recipients (44 ears) were recruited to participate in a longitudinal study to evaluate limitations at various locations along the auditory processing pathway. At the periphery, intra-cochlear neural health was estimated using focused psychophysical thresholds. Higher-order across-electrode intensity discrimination ability was assessed using psychophysical "spectral tilt." At the cortical level, cross-modal activation of the auditory cortex was assessed using functional near-infrared spectroscopy. Speech understanding outcomes were evaluated in competing multi-talker babble noise at 1-year post-device switch-on. We found that greater abilities to discriminate smaller across-electrode stimulation intensities (R2 = 0.138, p = 0.047) and smaller cross-modal activations of the auditory cortex (R2 = 0.216, p = 0.01) were significantly associated with better speech understanding outcomes in cochlear implant recipients. Furthermore, both measures contributed significantly to better predict speech understanding outcomes in a multiple regression model (Adj R2 = 0.312, p = 0.009). The results suggest that recipient-specific psychophysical and functional brain imaging metrics contribute significantly toward individual differences in speech understanding outcomes. Different recipients can be affected by different limitations, which can be identified using these tests, and therefore lead to potential patient-specific methods to improve their speech understanding.

Few studies have longitudinally evaluated Hashimoto's encephalopathy with anti-NH2-terminal α-enolase (anti-NAE) antibodies using detailed imaging and neuropsychological assessments. We present the case of a man in his 50s who presented with acute hallucinations, catatonia, seizures, and cognitive decline. Initial MRI revealed diffuse white matter hyperintensities, and SPECT revealed widespread hypoperfusion. These symptoms improved with immunotherapy, but progressive frontal and temporal atrophy and residual hypoperfusion appeared over 33 months. His cognitive function improved, but he remained impaired, with persistent disinhibition and perseveration. This case suggests that Hashimoto's encephalopathy with anti-NAE antibodies can cause lasting structural and functional brain abnormalities and cognitive impairments, requiring long-term neuroimaging and neuropsychological follow-up.

Integrated structural and functional brain imaging reveals biomarkers of disease activity in Crohn’s disease

Integrating non-Euclidean brain imaging data with Euclidean tabular data, such as clinical and demographic information, poses a substantial challenge for medical imaging analysis, particularly in forecasting future outcomes. While machine learning and deep learning techniques have been applied successfully to cross-sectional classification and prediction tasks, effectively forecasting outcomes in longitudinal imaging studies remains challenging. To address this challenge, we introduce a time-aware graph neural network model with transformer fusion (GNN-TF). This model flexibly integrates both tabular data and dynamic brain connectivity data, leveraging the temporal order of these variables within a coherent framework. By incorporating non-Euclidean and Euclidean sources of information from a longitudinal resting-state fMRI dataset from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the GNN-TF enables a comprehensive analysis that captures critical aspects of longitudinal imaging data. Comparative analyses against a variety of established machine learning and deep learning models demonstrate that GNN-TF outperforms these state-of-the-art methods, delivering superior predictive accuracy for predicting future tobacco usage. The end-to-end, time-aware transformer fusion structure of the proposed GNN-TF model successfully integrates multiple data modalities and leverages temporal dynamics, making it a valuable analytic tool for functional brain imaging studies focused on clinical outcome prediction.

High-resolution optical imaging of the cerebral cortex is severely hampered by strong light scattering induced by the opaque skull, posing a major obstacle to deciphering brain structure and function in vivo . Skull optical clearing, a technique that uses chemical cocktails to render the skull transparent, provides direct optical access to the cerebral cortex through the skull. However, existing chemical clearing techniques confer only modest skull transparency due to stringent time constraints and suboptimal chemical recipes. In this work, we developed a head-mounted optically transparent skull (HOTS) window technique. The head-mounted design overcomes clearing time constraints by extending the in vivo skull-clearing process from anesthetized, head-stabilized mice to awake, freely behaving mice. The clearing cocktail was substantially improved over previous recipes via systematic chemical screening tailored to the composition and structure of the skull. Through a series of in vivo and ex vivo experiments, we demonstrated that the HOTS window technique exhibits superior clearing efficacy, good reversibility, favorable biosafety, and broad application prospects. In particular, the HOTS window technique enables transcranial two-photon imaging of neurons at an unprecedented depth, exceeding 800 µm below the pia (permitting visualization layer 5 neurons), in adult mice, substantially outperforming existing skull-clearing methods and the use of thinned-skull windows. The achieved depth even rivals that of open-skull imaging. Even more critically, the HOTS window technique allows sensitive detection of subtle neuronal activity such as calcium transients evoked by whisker stimulation under anesthesia and faint but heterogeneous cAMP dynamics, through the skull, enabling functional investigations that were once restricted to destructive cranial windows.

ObjectiveTo examine how well acute stroke studies assessing upper limb sensorimotor capacity align with the Stroke Recovery and Rehabilitation Roundtable (SRRR) recommendations, focussing on the type of assessment tools used, study and participant characteristics, follow-up timings, and the use of clinical and multimodal data.DesignScoping review.Data sourcesEmbase, MEDLINE, PubMed, CINAHL, PsycINFO, Google Scholar, and Web of Science were searched for relevant studies published between 01 August 2017 and 30 September 2025.MethodsThis review included studies involving adults with stroke who underwent upper limb assessment during the acute phase. Data were extracted on clinical, structural, and functional assessments, as well as follow-up timing, study, and participant characteristics. Of the 3628 identified articles, 132 met the inclusion criteria.ResultsWhile global assessments (e.g. NIH stroke scale [NIHSS]) and impairment-level upper limb assessments (e.g. Upper-extremity Fugl-Meyer Assessment) were widely used, activity-level tools (e.g. Action Research Arm Test) were underrepresented. Structural brain imaging was common, though often used only diagnostically, while functional brain imaging and multimodal approaches were rare. Follow-up timing varied, with limited long-term tracking. Demographic reporting was inconsistent, with underrepresentation of young adults and women.ConclusionDespite progress, significant gaps remain in the standardisation and comprehensiveness of upper limb assessment in acute stroke research. Future studies should better align with SRRR recommendations to improve data comparability and scientific rigour.

Neuropathic chronic low-back pain (neuCLBP) is associated with worse clinical outcomes compared with non-neuropathic or axial CLBP (non-neuCLBP) and has limited effective nonsurgical treatment options, reflecting poor understanding of its underlying pathophysiology. In this study, we compared neuCLBP and non-neuCLBP patients using standardized clinical phenotyping of the neuropathic component alongside multimodal brain functional magnetic resonance imaging (fMRI). We hypothesized that, consistent with the definition of neuropathic pain as pain arising from injury to the somatosensory nervous system, neuCLBP patients would exhibit reduced thalamic volume and/or altered thalamic shape, reduced primary somatosensory cortex (S1) thickness, and altered resting-state functional connectivity of these structures compared with non-neuCLBP patients and pain-free healthy controls. Consistent with previous literature, we observed that neuCLBP patients (n = 28) presented with more severe clinical symptoms than non-neuCLBP patients (n = 28). Structurally, neuCLBP patients exhibited extensive differences in thalamic shape but no significant differences in thalamic volume or S1 gray matter thickness. By contrast, by examining resting-state thalamic connectivity gradient maps, we found that non-neuCLBP patients exhibited the most pronounced alterations in these gradients. This study is the first to combine multimodal fMRI with rigorous, standardized phenotyping to investigate neuCLBP. While our results may be influenced by greater symptom severity in the neuCLBP patients, they indicate that these patients may display distinct central plasticity patterns. The findings also highlight the importance of distinguishing between these clinical phenotypes to reduce heterogeneity in future studies.

Surface-based functional brain imaging analysis of major depressive disorder after electroconvulsive therapy.

How martial arts training affects psychological states and brain function and structure: An fMRI study.

Optically pumped magnetometers (OPMs) present a promising opportunity to advance magnetoencephalography (MEG), enhancing the accuracy of neuronal activity recordings due to their high spatiotemporal resolution. However, to fully realize the potential of OPM-MEG as an emerging brain functional imaging technology, it is essential to measure key indicators of neural dynamics, particularly phase–amplitude coupling (PAC). PAC is a fundamental mechanism for integrating information across different frequency bands and plays an important role in various cognitive functions and neurological disorders. Therefore, measuring PAC with OPM-MEG is a crucial step toward expanding its applications. In this study, brain signals under pitch sequence stimulation were recorded using OPM-MEG to analyze the PAC effect in the primary auditory cortex (Aud) and the inferior frontal gyrus (IFG), as well as the functional connectivity between brain regions. The findings were validated through EEG control experiments. The results indicated that the PAC effect measured by OPM-MEG was largely consistent with that measured by EEG, with OPM-MEG appearing to detect PAC more prominently under the current experimental conditions. The PAC of Aud exhibited a trend of initially increasing and then decreasing centered on the target pitch, showing hemispheric symmetry. The PAC of IFG showed variations under different pitch conditions and displayed right hemisphere lateralization. Functional connectivity analysis provided convergent evidence for the mechanisms underlying the PAC effect and suggested the reliability of the OPM-MEG system in capturing cross-frequency neural dynamics. To our knowledge, this study provides the first task-based evidence that OPM-MEG can measure PAC effects in cortical regions, offering an initial foundation for future investigations of brain dynamics using this technology.

This paper reviews the neural mechanism of delayed discounting, aiming to sort out the decision-making laws of individuals in instant reward and delayed reward selection and their brain base. In particular, it explores the involvement of the prefrontal cortex and the septum nucleus in delayed discounting, the relationship between neural connectivity and decision-making preferences, as well as the possible effects of neurostimulation on behavior. Existing studies have leveraged behavioral modeling, brain function imaging, and causal intervention methods to quantify individual preferences using the hyperbolic discounting model and discounting rate, while combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to elucidate the functional connectivity and temporal dynamics of the prefrontal cortex (PFC) and the septum nucleus in decision-making. At the same time, transcranial magnetic stimulation (TMS) is employed to investigate the effects of neural modulation on discounting rates. The results demonstrate that the prefrontal cortex promotes rational decision-making, while the septum nucleus boosts the immediate reward attractiveness, so the interaction between the two significantly affects the selection behavior. Besides, individuals with strong functional connections are more inclined to choose delayed rewards, and the EEG study reveals the timing characteristics of impulse and rational switching in decision-making. In addition, TMS interventions can modulate discounting rates, indicating that delayed discounting is amenable to change. However, most studies use college student samples and short intervention periods, highlighting the need for further research and improved behavioral interventions.

Extraversion and the resting brain: a coordinate-based meta-analysis of resting-state functional brain imaging studies.

BackgroundReducing opioid use is challenging due to limited evidence-based weaning methods and a lack of interventions to mitigate withdrawal symptoms. An emerging intervention using transcutaneous auricular neurostimulation (tAN) is being developed to reduce opioid withdrawal symptoms, but its mechanisms of action are not yet well understood. This is a clinical trial performed to investigate the mechanisms of tAN in managing pain and opioid withdrawal during opioid taper in adults with chronic pain.MethodsThis is a single-site, randomized, double-blind, and sham-controlled superiority framework trial during an inpatient opioid taper for participants on long-term opioid therapy for chronic pain. Participants are recruited for an inpatient stay at a large, academic medical center in the United States. Included participants are adults between 18 and 75 years of age who have the presence of pain more than half of the days in the past 6 months, are prescribed opioid medication, have a willingness to taper the opioid dose by at least 10%, and have a urine drug screen positive for the prescribed opioid but negative for illicit drugs and nonprescribed opioids. Participants are excluded with a condition affecting their safety of participation (e.g., epileptic seizures, current suicidal ideation, current abuse of illicit drugs or alcohol, pregnancy), a condition that precludes fMRI assessment (implanted medical device, claustrophobia), or a status affecting pain medication intake (e.g., surgery in the past month, opioid prescription dose > 200 morphine milligram equivalents per day, history of neurological diseases or traumatic brain injury, active treatment for cancer).Participants are randomized to receive either active tAN (n = 20) or sham tAN (n = 20). Both groups undergo a mild-to-moderate opioid taper on day 1 and are maintained at the reduced level for 4 days under inpatient medical supervision. The primary outcome measure, brain functional magnetic resonance imaging (fMRI), is used to measure BOLD signals and resting functional connectivity (z-value) of pain networks. Secondary outcome measures are self- and clinician-observed opioid withdrawal scales, behavioral assessment questionnaires, and quantitative sensory testing (QST) data.The first subject enrollment was completed from July 25 to 28, 2023. The total enrollment count was set to 40 with two arms of equal ratios. Randomization stratification by gender at birth was performed. The study physician, intervention-providing staff member, and outcome-assessing study coordinator each perform recruitment, and each is blinded to treatment group assignment.Safety and harm measures of opioid withdrawal will be assessed with the Clinical and Subject-reported Opiate Withdrawal Scores. Vital signs will be assessed three times per day, and adverse events will be recorded and reported as necessary.DiscussionUnderstanding the mechanisms of action of tAN will lead to the development of more effective future non-pharmacologic treatments in mitigating withdrawal while gradually tapering participants off prescription opioid management.Trial registrationClinicaltrials.gov, NCT05555485. Registered on 15 September 2022.

The high spatiotemporal resolution of optically pumped magnetometers (OPMs) makes them an essential tool for functional brain imaging, enabling accurate recordings of neuronal activity. However, physiological signals such as eye blinks and cardiac activity overlap with neural magnetic signals in the frequency domain, resulting in contamination and creating challenges for the observation of brain activity and the study of neurological disorders. To address this problem, an automatic physiological artifact removal method based on OPM magnetic reference signals and a channel attention mechanism is proposed. The randomized dependence coefficient (RDC) is employed to evaluate the correlation between independent components and reference signals, enabling reliable recognition of artifact components and the construction of training and testing datasets. A channel attention mechanism is subsequently introduced, which fuses features from global average pooling (GAP) and global max pooling (GMP) layers through convolution to establish a data-driven automatic recognition model. The backbone network is further optimized to enhance performance. Experimental results demonstrate a strong correlation between the magnetic reference signals and artifact components, confirming the reliability of magnetic signals as artifact references for OPM-MEG. The proposed model achieves an artifact recognition accuracy of 98.52% and a macro-average score of 98.15%. After artifact removal, both the event-related field (ERF) responses and the signal-to-noise ratio (SNR) are significantly improved. Leveraging the flexible and modular characteristics of OPM-MEG, this study introduces an artifact recognition framework that integrates magnetic reference signals with an attention mechanism. This approach enables highly accurate automatic recognition and removal of OPM-MEG artifacts, paving the way for real-time, automated data analysis in both scientific research and clinical applications.

Stimulation of the brain using transcranial focused ultrasound has gained a moment in research, opening a new horizon of possibilities in research and treatment in various fields of neurology and psychiatry. However, to date the method is still limited to specific application areas such as the treatment of patients with difficult-to-treat forms of focal epilepsy. The use of ultrasound in brain imaging in non-paediatric populations has been limited to interoperative scenarios. In the present talk an update is given on the high-risk high-gain project "AEGEUS“, funded by the European Research Council and aiming at developing a novel electroencephalographic-Ultrasound device for functional brain imaging and neurostimulation.The device is meant to combine the advantage of the electroencephalogram, providing excellent time-resolution, with the envisioned high resolution in space especially in deeper brain region of transcranial ultrasound. To date, the first experiments are set out to capture signals of neuronal origin with a first prototype. In the present talk, potential application areas in the research and treatment of motion sickness are projected alongside with the envisioned outcomes of the ongoing development and clinical testing of the novel device.

BackgroundWith the accelerating global aging population, the incidence of Alzheimer's disease (AD) continues to rise, while current pharmacological treatments remain limited in efficacy. Music intervention, as a safe and feasible non-pharmacological approach, has gained increasing clinical attention, though its mechanisms of action remain unclear.ObjectiveThis study aims to evaluate the effects of music intervention on cognitive function and brain network connectivity in people with mild AD, and to elucidate its neural mechanisms and provide evidence for clinical practice.MethodsA total number of 50 AD patients with mild dementia participated in the study. Participants were randomized to music-based intervention group (music-based intervention, 20 min, 3 times/week for 6 months) or control group (standard care). Assessments included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Neuropsychiatric Inventory (NPI), Word Fluency Test (WFT), World Health Organization-University of California, the Los Angeles Auditory Verbal Learning Test (WHO-UCLA-AVLT), and functional magnetic resonance imaging (fMRI). Data were analyzed using SPSS 20.0.Results47 participants completed the study. The music-based intervention group showed significant improvements in MoCA, GDS, NPI, WFT, and WHO-UCLA-AVLT scores (p < 0.05), with no change in MMSE. fMRI revealed enhanced frontal-temporal connectivity and increased angular gyrus activity.ConclusionsMusic-based intervention improves cognitive and neuropsychiatric outcomes in people with mild AD, likely through enhanced brain connectivity. This approach is feasible, and it supports the optimization of music-based intervention in clinical practice.

.SignificanceContinuous and longitudinal monitoring of cerebral blood flow (CBF) is critical for understanding brain pathophysiology and guiding interventions. Although rodents are the primary models in neuroscience, existing imaging modalities often fail to provide the optimal combination of low cost, high spatiotemporal resolution, wide head coverage, and sufficient penetration depth for small-animal brain imaging.AimLeveraging a clinical speckle contrast diffuse correlation tomography (scDCT) system, we aimed to develop an affordable, user-friendly, fast, and miniaturized scDCT (mini-scDCT) device tailored for depth-sensitive CBF imaging in small rodents.ApproachThe mini-scDCT replaces bulky and costly optoelectronic components with compact, low-cost alternatives while preserving imaging performance. It is mounted on a standard stereotaxic apparatus for portability and ease of use. Temporal resolution was improved by hardware synchronization and software optimization. System validation was performed using head-simulating phantoms and rodent models under various pathophysiological conditions.ResultsCompared with the original scDCT, the mini-scDCT achieved a fourfold cost reduction, a fivefold footprint reduction, and eightfold improvement in temporal resolution per source. Validation experiments confirmed the system’s depth sensitivity in head-simulating phantoms and its ability to detect both global and regional CBF changes in rodents, with results consistent with physiological expectations and prior studies.ConclusionThe mini-scDCT offers an affordable, user-friendly, depth-sensitive platform for functional brain imaging in rodent models. Its reduced cost and compact footprint enhance accessibility, whereas the improved spatiotemporal resolution enables diverse applications such as imaging brain functional connectivity in neuroscience research.