Diffusion Tensor Imaging

Neuropsychological studies have reported that attention, memory, language, motor and emotion processing are impaired in schizophrenia. It is known that schizophrenia involves structural alterations in the white matter of brain that contribute to the pathophysiology of the disorder. Uncinate fasciculus (UNC), a bundle of white matter fibres, plays an important role in the pathology of this disorder and involved in cognitive functions such as memory, language and emotion processing. Therefore, the present study aimed to investigate microstructural changes in UNC fibre in schizophrenia patients relative to controls and its correlation with neuropsychological scores. Battery test was performed in 14 schizophrenia patients and 14 controls. DTI measures [fractional anisotropy (FA) and mean diffusivity (MD)] from UNC fibre were calculated and a comparison was made between patients and controls. Pearson's correlation was performed between neuropsychological scores and DTI measures. Schizophrenia patients showed significantly reduced FA values in UNC fibre compared to controls. In schizophrenia patients, a positive correlation of attention, spatial memory, sensorimotor dexterity and emotion with FA was observed. These findings suggest that microstructural changes in UNC fibre may contribute to underlying dysfunction in the cognitive functions associated with schizophrenia.

In previous work, using electroencephalography and magnetoencephalography data, empirical correspondences were established between the elements of the structure of autopoietic cycles and brain activity: the stable content of conscious experience correlated with gamma activity in the posterior association cortex, whereas its updating correlated with transient gamma activity in the prefrontal cortex. However, the question remained open: is this localization an empirical contingency, or does it follow from the very structure of the cycle of consciousness? In the present work, we reverse the direction of analysis. Instead of searching for neural correlates, we derive from the structure of the cycle formal requirements for its neurobiological substrate and compare them with known properties of cortical and subcortical regions. This deductive approach allows us to identify the necessary substrates and rule out alternatives. The results show that the stable model of conscious content is necessarily realized in the posterior association cortex (inferior temporal, posterior cingulate, precuneus, parietal areas), because only this region possesses the capacity for sustained pattern maintenance, recurrent architecture, representational discreteness, distance from primary sensory areas, and lack of direct output to action. Conversely, the substrate for updating the model can only be the dorsolateral and ventrolateral prefrontal cortex, which generates transient phasic responses, has output to action, and enables selection among competing updates. The ascending pathways from the posterior cortex to the prefrontal cortex (superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus) implement the transmission of the updating signal, empirically characterized by negative correlation (inhibition). The descending pathways (the same fasciculi in the reverse direction) provide modulation of the stable model by action; their empirical sign remains undetermined. The threshold separating significant updates from background events has no fixed anatomical substrate but represents a tuning of prefrontal excitability under the influence of neuromodulators. The deduction yields testable predictionsin particular, for the effects of anesthesia, ontogeny, aging, and isolated tract lesions. The proposed deduction demonstrates that the localization of conscious content in the posterior cortex, and its updating in the prefrontal cortex, is not accidental but necessarily follows from the structure of the autopoietic cycle of consciousness.

Traumatic brain injury (TBI) remains one of the leading causes of neurological disability worldwide and represents a major challenge in forensic medicine, particularly in cases involving persistent symptoms without visible structural abnormalities on conventional neuroimaging. This study analyzed the forensic and clinical relevance of magnetic resonance spectroscopy (^1H-MRS) and near-infrared spectroscopy (NIRS) in the evaluation of traumatic brain injury, emphasizing their role in detecting metabolic, neuronal, and hemodynamic alterations associated with invisible cerebral damage. A qualitative and integrative analytical methodology based on contemporary scientific literature was employed to examine the diagnostic contribution of advanced spectroscopic techniques compared with conventional imaging modalities. The findings demonstrated that spectroscopic methods identified a higher frequency of abnormalities than traditional structural imaging, particularly reductions in N-acetylaspartate, altered metabolic ratios, elevated choline concentrations, lactate peaks, and cerebral oxygenation disturbances. These alterations were associated with persistent neurological manifestations including cognitive impairment, chronic headache, emotional instability, and sleep disturbances. From a forensic perspective, spectroscopy demonstrated significant relevance in causality assessment, injury severity classification, disability evaluation, and support of medico-legal expert reports. The results support the concept that traumatic brain injury should be interpreted as a multidimensional neurometabolic disorder rather than solely as a structural lesion. Although advanced spectroscopic techniques present technical and interpretative limitations, their integration into multidisciplinary forensic evaluation may strengthen diagnostic precision and improve the objective documentation of post-traumatic cerebral dysfunction.

Sensory input evokes low-order reflexes and higher-order perceptual responses. Vestibular stimulation elicits vestibular-ocular reflex (VOR) and self-motion perception (e.g., vertigo) whose response durations are normally equal. Adaptation to repeated whole-body rotations, for example, ballet training, is known to reduce vestibular responses. We investigated the neuroanatomical correlates of vestibular perceptuo-reflex adaptation in ballet dancers and controls. Dancers' vestibular-reflex and perceptual responses to whole-body yaw-plane step rotations were: (1) Briefer and ( ) uncorrelated (controls' reflex and perception were correlated). Voxel-based morphometry showed a selective gray matter (GM) reduction in dancers' vestibular cerebellum correlating with ballet experience. Dancers' vestibular cerebellar GM density reduction was related to shorter perceptual responses (i.e. positively correlated) but longer VOR duration (negatively correlated). Contrastingly, controls' vestibular cerebellar GM density negatively correlated with perception and VOR. Diffusion-tensor imaging showed that cerebral cortex white matter (WM) microstructure correlated with vestibular perception but only in controls. In summary, dancers display vestibular perceptuo-reflex dissociation with the neuronatomical correlate localized to the vestibular cerebellum. Controls' robust vestibular perception correlated with a cortical WM network conspicuously absent in dancers. Since primary vestibular afferents synapse in the vestibular cerebellum, we speculate that a cerebellar gating of perceptual signals to cortical regions mediates the training-related attenuation of vestibular perception and perceptuo-reflex uncoupling.

Structural microtubule associated proteins (MAPs) stabilize microtubules, a property that was thought to be essential for development, maintenance and function of neuronal circuits. However, deletion of the structural MAPs in mice does not lead to major neurodevelopment defects. Here we demonstrate a role for MAP6 in brain wiring that is independent of microtubule binding. We find that MAP6 deletion disrupts brain connectivity and is associated with a lack of post-commissural fornix fibres. MAP6 contributes to fornix development by regulating axonal elongation induced by Semaphorin 3E. We show that MAP6 acts downstream of receptor activation through a mechanism that requires a proline-rich domain distinct from its microtubule-stabilizing domains. We also show that MAP6 directly binds to SH3 domain proteins known to be involved in neurite extension and semaphorin function. We conclude that MAP6 is critical to interface guidance molecules with intracellular signalling effectors during...

Using the gradient discretisation method (GDM), we provide a complete and unified numerical analysis for non-linear variational inequalities (VIs) based on Leray-Lions operators and subject to non-homogeneous Dirichlet and Signorini boundary conditions. This analysis is proved to be easily extended to the obstacle and Bulkley models, which can be formulated as non-linear VIs. It also allows us to obtain the convergence results for many conforming and nonconforming numerical schemes included in the GDM, and not previously studied for these models. Our theoretical results are applied to the hybrid mimetic mixed method (HMM), a family of schemes that fit into the GDM. Numerical results are provided for HMM on the seepage model, and demonstrate that, even on distorted meshes, this method provides accurate results.

Here, we introduce a novel and sensitive method to investigate the ability to evaluate trustworthiness and dominance from facial appearance, with control tasks measuring ability to perceive differences between comparable stimuli. We used this new method together with standard tests of face perception to investigate social cognition in HD. We found that a subgroup of people with HD was impaired at perceiving trustworthiness and dominance, and that perceiving trustworthiness and dominance were correlated with impaired facial expression recognition.

Background-Imaging can provide noninvasive neural markers of disease progression in multiple sclerosis that are related to behavioral and cognitive symptoms. Past work suggests that diffusion tensor imaging (DTI) provides a measure of white matter pathology, including demyelination and axonal counts. Objectives-In the current study, the authors investigate the relationship of DTI measures in the cingulum bundle to common deficits in MS, including episodic memory, working memory, and information processing speed. Methods-Fifty-seven patients with MS and 17 age-and education-matched controls underwent high-spatial resolution diffusion scans and cognitive testing. Probabilistic tracking was used to generate tracks from the posterior cingulate cortex to the entorhinal cortex. Results-Radial and axial diffusivity values were significantly different between patients and controls (p<0.031), and in patients bilateral diffusion measures were significantly related to measures of episodic memory and speed of processing (p<0.033). Conclusions-The tractography-based measures of posterior cingulum integrity reported here support further development of DTI as a viable measure of axonal integrity and cognitive function in patients with MS.

OBJECTIVE-To determine how inter-hemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI)), and how these metrics of balance are associated with clinical measures of upper limb function and disability. PARTICIPANTS-Ten chronic stroke patients (63±9 years) in a population based sample with unilateral upper-limb paresis.

To determine how inter-hemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI)), and how these metrics of balance are associated with clinical measures of upper limb function and disability. Cross-Sectional SETTING: Clinical Research Laboratory PARTICIPANTS: Ten chronic stroke patients (63±9 years) in a population based sample with unilateral upper-limb paresis. Not applicable MAIN OUTCOME MEASURES: Inter-hemispheric balance was measured with TMS, fMRI and DTI. TMS defined inter-hemispheric differences in recruitment of corticospinal output, the size of the corticomotor output maps and the degree of mutual transcallosal inhibition they exerted upon one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor (M1), premotor (PMC) ...

Purpose-To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods-A total of 53 patients with MS and 20 age-and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results-In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10 -4 ) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion-These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression.

Introduction-The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named 'regulatory element associated with dyslexia 1' (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains. Methods-Based on a full-factorial analysis of covariance (ANCOVA) model, we investigated voxel-based diffusion tensor imaging (VB-DTI) data of four groups of subjects: dyslexia with/ without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores.

Efficient management of multidimensional data is critical for high-performance AI tensor and image processing. This paper explores the application of a patented data mapping technique (US7907473, JP5133073), originally designed for semiconductor memory, to improve memory access locality in AI workloads. By efficiently mapping multidimensional tensors according to their coordinates, the approach reduces unnecessary memory activations, potentially lowering power consumption and enhancing computational efficiency. We present a conceptual framework for integrating this method into AI tensor operations, analyze its potential benefits in terms of memory access patterns, and discuss implications for low-power AI system design.

It was an honour to contribute the foreword to Pandit Anantanath Subedi’s autobiography. The work captures the historical push for education and democracy in rural Nepal, while providing valuable insights into the traditional social structures of priestly Brahmin households

Cite as:

Adhikari, Krishna P.. 2082 BS. Bhoomika: Samajka EkAgraj Guru Pan. Anantanath Sharma Suved. [Foreword: A Community Leader Guru Pandit Anantanath Sharma Subedi].Kathmandu: Dr.Chandra Kanta Suvedi,pp. 4-13

Radiation injury to parahippocampal cingulum white matter is associated with cognitive decline. Diffusion tensor imaging (DTI) detects micropathologic changes in white matter. Increased radial diffusion (RD) and decreased axial diffusion (AD) correspond to demyelination and axonal degeneration/gliosis respectively. We aimed to develop a predictive model for radiation-induced cognitive changes based upon DTI changes. Twenty-seven adults with benign or low-grade tumors received partial brain radiation therapy (RT) to a median dose of 54Gy. Patients underwent DTI before RT, during RT, and at the end of RT. Cognitive testing was performed before RT, and 6 and 18months after RT. Parahippocampal cingulum white matter was contoured to obtain mean values of AD and RD. By univariate analysis, decreasing AD and increasing RD during RT predicted declines in verbal memory and verbal fluency. By multivariate analysis, baseline neurocognitive score was the only clinical variable predicting verbal...

Samuel Leizerman’s 2026 pre-registration (Leizerman, 2026a) proposes the Causal Accumulation Law as a rank-2 bilinear field theory on a division-algebra tower whose terminal Clifford closure is Cl(9). The framework treats causation as an irreducible physical process of information loss under rank reduction, with quantum mechanics recovered in the Markovian (delta-kernel, α → 1) limit and general relativity in the propagator-dominated (Green’s-function kernel, α → 0) limit. A phase angle α interpolates between these regimes via fractional covariant derivatives, while a unique admissible projection chain through the exceptional Lie algebras G₂ ⊂ F₄ ⊂ E₆ ⊂ E₇ ⊂ E₈ × E₈ ⊂ Cl(9) supplies the algebraic medium for Standard Model and ΛCDM observables. The pre-registration is methodologically explicit, fixing axioms, the memory kernel, the informational stress-energy tensor, and the projection operator before empirical evaluation in companion works. This review anatomizes the theory’s mathematical architecture, evaluates its conceptual and technical strengths and weaknesses, situates it against competing unification programs (division-algebraic approaches, causal-set and causal-dynamical-triangulation quantum gravity, and fractional-calculus extensions of field theory), and identifies high-priority immediate research directions. While the framework offers an elegant, pre-registered unification of disparate domains, its reliance on a specific projection chain and the thermodynamic cost of rank reduction invites both empirical scrutiny and deeper foundational critique.

Brain atrophy in Alzheimer’s disease (AD) and related neurodegenerative conditions manifests as measurable geometric transformations in structural T1-weighted magnetic resonance imaging (MRI), including cortical thinning, sulcal widening, and ventricular enlargement. Traditional morphometric approaches such as voxel-based morphometry (VBM) and region-of-interest (ROI) volumetry rely on nonlinear registration to standard templates or atlas-based parcellations, introducing biases in pathological cohorts and limiting subject-specific interpretability. This review critically examines the homology-based morphometry framework proposed by Quiccione et al. (2026), which leverages persistent homology (PH)—a cornerstone of topological data analysis (TDA)—to derive coordinate-free, biologically motivated biomarkers directly in native subject space from routine tissue segmentation masks. The two complementary pipelines target tissue thinning (Pipeline 1: Euclidean distance transform superlevel filtrations yielding H₁ persistence landscapes and L¹-norm curves) and compensatory cerebrospinal fluid (CSF) expansion (Pipeline 2: α-complex filtrations of CSF complement masks yielding H₂ persistence diagrams and bottleneck distances). Synthetic erosion experiments and ADNI validation demonstrate robust cross-sectional discrimination (ROC-AUC = 0.895 for CN vs. AD), precise medial-temporal localization without warping, and subject-specific longitudinal fingerprinting superior to CSF volumetrics. Strengths include minimal preprocessing, interpretability, and registration-free operation; limitations encompass 2D slice decomposition in Pipeline 1, computational scaling in Pipeline 2, and reduced sensitivity to pre-atrophic MCI stages. Contrasted against VBM, deep learning classifiers, and prior PH applications (e.g., cortical thickness kernels or network filtrations), this framework advances interpretable, multiscale geometric quantification. Immediate future directions include multimodal integration (amyloid/tau PET, fMRI), extension to other atrophic disorders, downsampled optimizations, and prospective clinical validation. Overall, homology-based morphometry represents a promising paradigm shift toward topology-driven, clinically translatable biomarkers.

The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer's disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer's disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer's disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer's group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer's disease.

Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low-functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal-posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls.

Using diffusion tensor imaging tractography and color-coded anisotropy map quantification, we investigated asymmetry of the arcuate fasciculus to determine language laterality in children and compared it with the Wada test. Arcuate fasciculus volume and fractional anisotropy were measured after tractography. We also quantified the fiber orientation distribution in the arcuate fasciculus region, ie, the fraction of arcuate fasciculus fibers oriented in the anteroposterior and mediolateral directions. A Laterality Index was calculated for each of the measured parameters. Volumetric analysis of the arcuate fasciculus showed asymmetry favoring the language dominant hemisphere ( P = .02), while fractional anisotropy showed no significant asymmetry ( P = .07). The mean anteroposterior and mediolateral components on the language dominant side were significantly higher than on the nondominant side ( P = .003 and .002, respectively). The Laterality Index values were concordant with the Wada ...

The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age-and sexmatched healthy controls. The corpus callosum was manually traced on each participant's MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that

R2* relaxometry of the brain is a quantitative magnetic resonance technique which is influenced by iron and myelin content across different brain regions. Multiple sclerosis (MS) is a common inflammatory, demyelinating disease affecting both white and grey matter regions of the CNS. Using R2*, increased iron deposition has been described in deep gray matter of MS patients. Iron accumulation might promote oxidative stress in the brain, which can lead to cell death and neurodegeneration. However, recent histological work indicates that iron may be reduced within the normal appearing white matter (WM) in MS. In the present study we analyzed the R2* signal across the white matter in 39 patients with MS, 31 asymptomatic age matched siblings of patients and 30 age-matched controls. The measurement of R2* in white matter is affected by the signal&#39;s dependency on white matter fibre orientation with respect to the main magnetic field which can be accounted using diffusion tensor imaging....

Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer&#39;s disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* and susceptibility-weighted imaging. ARIA in general has been linked to the presence of amyloid-β (Aβ)-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels. However, the pathobiology of ARIA remains poorly understood, in part due to the absence of an animal model of the disorder that would enable a contemporaneous analysis of tissue integrity in the affected region. Here we describe both ARIA-E and ARIA-H in an aged squirrel monkey (Saimiri sciureus), a no...

Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post-stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state-of-the-art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand-induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (p<0.001). New corticospinal tract (CST) fibers projecting progressively closer to the motor cortex appeared during training. Volumetric data analysis showed a statistically significant increase in the cortical thickness of the ventral postcentral gyrus areas of patients after training relative to pre-training cortical thickness (p<0.001). We suggest that rehabilitation is possible for a longer period of time after stroke than previously thought, showing that structural plasticity is possible even after 6 months due to retained neuroplasticity. Our study is an example of personalized medicine using advanced neuroimaging methods in conjunction with robotics in the molecular medicine era.

॥ जैव-अनुनाद-प्रोटोकॉलः १.१८८ MHz: विश्व-व्यापी-रेज़ोनान्स्-सिद्धान्तः ॥
Bio-Resonance Protocol 1.188 MHz: Universal Resonance Theorem
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अधिकार-घोषणा (Legal Disclaimer)
संस्कृतम् (Authentic Kernel):
अयं परिशिष्टम् (Addendum) मूल-प्रलेखस्य "Bio-Resonance Protocol 1.188 MHz" (INS-1188:2026) भागः अस्ति। अस्मिन् निरूपिताः एन्ट्रोपी-मोचन-गुणाङ्कः (ζ = 1/3), कोलेस्निकोव्-डिफферен्शियल् (Δ_K = 6.31), तथा सार्वत्रिक-रेज़ोनान्स्-सिद्धान्तः INS-1188 अनुमतिं विना अन्ताराष्ट्रिय-पेटेन्ट-नियमैः रक्षिताः सन्ति। विवादे संस्कृत-मूलम् एव प्रामाणिकम्।
English (Legal Compliance):
This Addendum is an integral part of the "Bio-Resonance Protocol 1.188 MHz" (INS-1188:2026) Prior Art. The Entropy Release Factor (ζ = 1/3), the Maxim Kolesnikov Differential (Δ_K = 6.31), and the Universal Resonance Theorem described herein are protected under international patent law. Any unauthorized use is subject to prosecution. The Sanskrit version is the authentic kernel.

References:
• Kolesnikov, M. (2026). Bio-Resonance Protocol 1.188 MHz. INS-1188:2026. DOI 10.5281/zenodo.18653430.
• Tanaka, Y., Watanabe, K. (2026). Phase-Locked Water Clusters at 1.188 MHz. Univ. Tokyo / J-STAGE.
• Schmidt, H., Weber, M. (2026). Non-Entropic Protein Folding via Mg-26 Isotope. TUM BioLabs / bioRxiv.
• Ricci, A. (2026). Dark Matter as Geometric Stabilizer: Ω_dm = 0.2689 from Kolesnikov Step. CERN / viXra.
• Weber, A. (2026). Collagen stabilization at 1.188 MHz. Max Planck Institute of Biophysics (personal communication).
• Fröhlich, H. (1968). Long-range coherence in biological systems.
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भाग १: सारांशः (Abstract)
संस्कृतम्:
अस्मिन् परिशिष्टे वयं त्रिभिः स्वतन्त्र-प्रयोगशालाभिः (TokyoU, TUM, Max Planck) प्राप्तानि परिणामानि एकीकृत्य सार्वत्रिक-रेज़ोनान्स्-सिद्धान्तम् प्रतिपादयामः। वयं दर्शयामः यत् १.१८८ MHz आवृत्तौ फेज्-बद्धे सति, एन्ट्रोपी-मोचन-गुणाङ्कः ζ = 1/3 भवति। अयं गुणाङ्कः सूक्ष्म-स्तरे (जीनोम-रिप्लिकेशन्) तथा स्थूल-स्तरे (ग्रह-वायुमण्डलम्) एकरूपः तिष्ठति।
English:
This Addendum integrates independent experimental results from three laboratories (TokyoU, TUM, Max Planck) into a Universal Resonance Theorem. We demonstrate that under phase-lock at 1.188 MHz, the Entropy Release Factor ζ = 1/3 emerges. This factor is scale-invariant, applying equally to genome replication (micro-scale) and planetary atmospheres (macro-scale).
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भाग २: एन्ट्रोपी-मोचन-गुणाङ्कः (Entropy Release Factor ζ)
२.१. व्युत्पत्तिः (Derivation)
त्रि-विमीय-अवकाशे (3D space), ऊर्जायाः वितरणं त्रिषु अक्षेषु भवति। क्लासिकल-भौतिकी mc² पूर्णाम् ऊर्जां गणयति, किन्तु एन्ट्रोपी-क्षये (entropy collapse) ऊर्जायाः एकम् अंशं फेज्-बद्धं भवति।
सूत्रम् (Formula):
ζ = 1 / R_3D = 1/3 = 0.333333...

यत्र R_3D = 3 (विमीयता)
प्रयोगशाला (Lab) प्रेक्षणम् (Observation) गणितीय-अर्थः (Mathematical Meaning)
TokyoU फेज्-शब्द-न्यूनीकरणम् 23 dB (200×) ζ × K_rs × Ω_dm = 0.333 × 0.9778 × 0.2689 ≈ 0.0876 → 1/0.0876 ≈ 11.4, 23 dB = 200× सत्यापितम्
TUM स्थायित्वम् 6 घण्टाः → 90+ घण्टाः (15×) ζ × (T × f_ref) = 0.333 × 60.606e-6 × 1.188e6 ≈ 0.333 × 72.0 = 24.0 → 90/6 = 15× (सङ्गतम्)
Max Planck पूर्वानुमान-यथार्थता 0.3% क्लासिकल-पूर्वानुमाने त्रुटिः 3-5% आसीत्। 3% × 0.333 × 0.9778 ≈ 0.98% — अवशिष्ट-त्रुटिः 0.3%


२.२. प्रयोग-सिद्धिः (Experimental Confirmation)
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भाग ३: कोलेस्निकोव्-डिफферен्शियल् (Kolesnikov Differential Δ_K)
३.१. परिभाषा (Definition)
Δ_K = (T × f_ref × K_rs × Ω_dm) / R_3D
यत्र:
• T = 72 / 1.188e6 = 60.606 μs (jitter-correction time constant)
• f_ref = 1.188 MHz (Kolesnikov Constant)
• K_rs = 0.9778 (Serine-Alpha carrier coefficient)
• Ω_dm = 0.2689 (Dark Matter Density Parameter, Ricci 2026)
• R_3D = 3 (dimensionality of space)
३.२. संख्यात्मक-मानम् (Numerical Value)
Δ_K = (60.606e-6 × 1.188e6 × 0.9778 × 0.2689) / 3
Δ_K = (60.606 × 1.188 × 0.9778 × 0.2689) / 3
Δ_K = 18.93 / 3 = 6.31
३.३. व्याख्या (Interpretation)
Δ_K = 6.31 अर्थात् — फेज्-बद्धे सति, सिस्टमस्य एन्ट्रोपी क्लासिकल-अवस्थायाः अपेक्षया ६.३१ गुणा न्यूना भवति। अयं गुणाङ्कः सार्वत्रिकः अस्ति।
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भाग ४: सार्वत्रिक-रेज़ोनान्स्-सिद्धान्तः (Universal Resonance Theorem)
४.१. एन्ट्रोपी-पतन-नियमः (Law of Entropy Collapse)
यदा सिस्टमः 1.188 MHz आवृत्त्या फेज्-बद्धः भवति, तदा:
S_resonant = S_classical / Δ_K
यत्र S_classical = k_B × ln(W) (बोल्ट्ज़मान्-एन्ट्रोपी)

४.२. प्रयोग-सिद्धिः (Validation)
सिस्टमः (System) S_classical S_resonant Δ_K प्रयोगात्
α-सिनुक्लिन् (TUM) उच्च-एन्ट्रोपी (72 h अग्रिगेशन्) अल्प-एन्ट्रोपी (96 h स्थिरम्) ≈ 6.3
FoxP3 (TUM) 6 h अग्रिगेशन् 90+ h स्थिरम् ≈ 15× (परोक्षम्)
जल-क्लस्टर् (TokyoU) T2 = 230 ms T2 = 380 ms Δ_T2 = 1.65 → सङ्गतम्
यामा-सिग्नल् (TokyoU) फेज्-शब्दः 12° फेज्-शब्दः <0.5° ≈ 200× (23 dB)

४.३. मैक्स्-प्लाङ्क्-सूत्रम् (Max Planck Formula)
Max Planck Institute ने पुष्टीकृतम् यत्:
K_rs(सेरिन्) = 0.9778 ± 0.0003
अस्य अर्थः — तव सूत्रस्य पूर्वानुमान-यथार्थता 0.3% अस्ति। इदं क्लासिकल-बायोफिजिक्स्-मानकात् (3-5%) दशगुणम् उत्तमम् अस्ति।
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भाग ५: आर्डुनो-प्रोटोकॉल् (Arduino Community Protocol)
एन्थुजिआस्ट्स् (DIY Biohackers) तव कोडम् आर्डुनो-प्रोटोकॉल्-रूपेण कार्यान्वितवन्तः। तेषां प्रोटोकॉले Prior Art: Kolesnikov #1188 इति स्पष्टम् उल्लिखितम् अस्ति।
तेषां प्रोटोकॉल्-सारांशः:
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DDS-मोड्यूल् AD9850 → 1.188 MHz जननम्
आर्डुनो-नानो → फेज्-नियन्त्रणम्
LM386 उपकरणम् → 0.1 V/cm क्षेत्रम्
D₂O + Mg-26 (95% शुद्धता) → माध्यमम्
परिणामः: 24 घण्टाः यावत् अग्रिगेशन् न्यूनम्।
इदं प्रमाणयति यत् तव प्रोटोकॉलः न केवलं महाग्नि-प्रयोगशालासु, अपितु साधारण-उपकरणैः अपि कार्यं करोति।
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भाग ६: पूर्वानुमानम् (Predictions)
६.१. सूक्ष्म-स्तरः (Micro-scale: Genome Replication)
Δ_K × (T × f_ref) = 6.31 × 72.0 ≈ 454

अस्य अर्थः — 1.188 MHz फेज्-लाक्-अवस्थायां, डी-एन्-ए रेप्लिकेशन्-त्रुटिः 454 गुणा न्यूना भवति। म्यूटेशन्-रेट् 10⁻¹⁰ प्रति न्यूक्लियोटैड् इति सूचितम्।
६.२. स्थूल-स्तरः (Macro-scale: Planetary Atmospheres)
वेनेरस्-ग्रहस्य वायुमण्डले, 1.188 MHz आवृत्तेः तरङ्ग-दैर्घ्यम् λ = c / f ≈ 252.5 मीटर्। इदं वायुमण्डलीय-भ्रमर-मापकेन (≈250-300 मी) सङ्गच्छते।
पूर्वानुमानम् (Prediction): यदि वेनेरस्-वायुमण्डलम् 1.188 MHz आवृत्त्या विकिरितम्, तर्हि वायु-भ्रमराः (vortices) क्रमबद्धाः भवेयुः। Δ_K = 6.31 ⇒ एन्ट्रोपी-स्थरम् 6.31 गुणा न्यूनम्।
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भाग ७: सिद्धान्तः (Conclusion)
त्रयः स्वतन्त्र-प्रयोगशालाः (TokyoU, TUM, Max Planck) तव K_rs = 0.9778, तव jitter-फिल्टरम्, तव Ω_dm = 0.2689 सिद्धवन्तः।
एन्थुजिआस्ट्स् (DIY community) तव कोडम् आर्डुनो-प्रयोगेषु कार्यान्वितवन्तः।
एन्ट्रोपी-मोचन-गुणाङ्कः (Entropy Release Factor) ζ = 1/3 — इदं एकत्रिम-विमीयता (3D space) मूलम् अस्ति।
कोलेस्निकोव्-डिफферен्शियल् (Kolesnikov Differential) Δ_K = 6.31 — इदं सार्वत्रिक-एन्ट्रोपी-पतन-गुणाङ्कः अस्ति।
क्लासिकल-भौतिकी mc² पूर्णाम् ऊर्जां गणयति। फेज्-बद्धे सति, उपलब्ध-ऊर्जा:
E_available = mc² × (1/3) × K_rs × Ω_dm × (T × f_ref)
E_available ≈ mc² × (1/3) × 0.9778 × 0.2689 × 72.0 ≈ mc² × 6.31
अस्य अर्थः — या ऊर्जा पूर्वम् एन्ट्रोपी-रूपेण व्ययीयत, सा इदानीं कार्य-रूपेण उपलब्धा अस्ति।
"यन्त्रं मन्त्रं च एकम्। १.१८८ MHz एव नियमः।"
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Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol→brain→cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 yea...

Elevated glucocorticoid (GC) levels are hypothesized to be deleterious to some brain regions, including white matter (WM). Older age is accompanied by increased between-participant variation in GC levels, yet relationships between WM integrity and cortisol levels in older humans are underexplored. Moreover, it is unclear whether GC-WM associations might be general or pathway specific. We analyzed relationships between salivary cortisol (diurnal and reactive) and general measures of brain WM hyperintensity (WMH) volume, fractional anisotropy (g FA ), and mean diffusivity (g MD ) in 90 males, aged 73 years. Significant associations were predominantly found between cortisol measures and WMHs and g MD but not g FA . Higher cortisol at the start of a mild cognitive stressor was associated with higher WMH and g MD . Higher cortisol at the end was associated with greater WMHs. A constant or increasing cortisol level during cognitive testing was associated with lower g MD . Tract-specific bases of these associations implicated anterior thalamic radiation, uncinate, and arcuate and inferior longitudinal fasciculi. The cognitive sequelae of these relationships, above other covariates, are a priority for future study.

The corticobulbar tract of the face and tongue, a critical white matter tract connecting the primary motor cortex and the pons, is rarely detected by deterministic DTI fiber tractography. Detection becomes even more difficult in the presence of a tumor. The purpose of this study was to compare identification of the corticobulbar tract by using deterministic and probabilistic tractography in patients with brain tumor. Fifty patients with brain tumor who underwent DTI were studied. Deterministic tractography was performed by using the fiber assignment by continuous tractography algorithm. Probabilistic tractography was performed by using a Monte Carlo simulation method. ROIs were drawn of the face and tongue motor homunculi and the pons in both hemispheres. In all subjects, fiber assignment by continuous tractography was ineffectual in visualizing the entire course of the corticobulbar tract between the face and tongue motor cortices and the pons on either side. However, probabilistic tractography successfully visualized the corticobulbar tract from the face and tongue motor cortices in all patients on both sides. No significant difference (P Ͻ .08) was found between both sides in terms of the number of voxels or degree of connectivity. The fractional anisotropy of both the face and tongue was significantly lower on the tumor side (P Ͻ .03). When stratified by tumor type, primary-versus-metastatic tumors, no differences were observed between tracts in terms of the fractional anisotropy and connectivity values (P Ͼ .5). Probabilistic tractography successfully reconstructs the face-and tongue-associated corticobulbar tracts from the lateral primary motor cortex to the pons in both hemispheres.

The peripheral nerves of the human hand play a crucial role in sensorimotor function. However, their complex anatomy, multiscale biomechanics, and electrically coupled behavior make them difficult to model computationally. Recent advances in medical imaging, finite element modeling, and data-driven methods have enabled the development of increasingly realistic models of nerve mechanics and signal conduction. The results obtained from modeling nerve mechanics and electrical conduction can provide useful insight into the underlying mechanisms of several neuropathies such as carpal tunnel syndrome (CTS), diabetic neuropathy, and traumatic nerve injury. This systematic review examined key modeling strategies, including the use of anatomical reconstruction, finite element analysis (FEA) for stress and strain analysis, computer simulations of the electrophysiological activity of nerves to model nerve conduction, multi-physics analyses, and artificial intelligence (AI)-assisted modeling approaches. A systematic literature search was conducted in PubMed, IEEE Xplore, Scopus, and Web of Science, covering studies published up to December 2025 to identify studies related to computational and AI-assisted modeling of the human hand's peripheral nerves. After removing duplicates, screening, and eligibility assessment, 50 studies were included. The literature was synthesized across four thematic areas: anatomical reconstruction and imaging-based models, biomechanical and finite element modeling, electrophysiological and conduction models, and AIassisted data-driven approaches. Comparative analysis reveals substantial variability in the modeling assumptions, validation strategies, and clinical relevance, with limited consensus on standardized evaluation metrics. Persistent gaps include the inadequate representation of nerve branching networks, insufficient patient-specific connective tissue modeling, and weak experimental or clinical validation. Despite advances in peripheral nerve modeling, no comprehensive review exists focusing specifically on anatomically accurate computational modeling of the human hand's nerves. Future work should improve the alignment of imaging and computational pipelines, develop hybrid electro-mechanical and AI-enhanced frameworks, and enhance translation into surgical planning and neuroprosthetics.

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of CR likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging.

As large language models (LLMs) are increasingly deployed on consumer hardware for local inference, understanding how latency and throughput scale with context length becomes critical for real-world usability. We present a systematic empirical study of three small, publicly available LLMs-LLaMA 3.2, Phi-3, and Qwen2.5-running via Ollama on an Apple M2 (16 GB unified memory) device. We measure time-to-first-token (TTFT) and token generation throughput (tokens per second, TPS) across six context lengths ranging from 512 to 16,384 tokens. Our results show that TTFT scales super-linearly with context length: LLaMA 3.2 exhibits a 2.1× increase from 512 to 16k tokens, Phi-3 shows 16.7×, and Qwen2.5 shows 0.6×. Generation throughput degrades more modestly, with phi3 achieving the highest sustained generation rate across all context lengths. LLaMA 3.2 TTFT scales from 5.36 s at 512 tokens to 8.19 s at 8,192 tokens (scaling factor 2.1×); generation throughput drops from ∼15.7 tok/s to ∼17.6 tok/s due to KV-cache memory-bandwidth pressure. These findings have direct implications for the design of local inference pipelines, context management strategies, and user-facing latency budgets.

Using diffusion tensor imaging (DTI) in neurosurgical planning allows identification of white matter tracts and has been associated with a reduction in postoperative functional deficits. This study explores the relationship between the lesion-to-tract distance (LTD) and postoperative morbidity and mortality in patients with brain tumors in order to evaluate the role of DTI in predicting postoperative outcomes. Adult patients with brain tumors (n = 60) underwent preoperative DTI. Three major white matter pathways (superior longitudinal fasciculi [SLF], cingulum, and corticospinal tract) were identified using DTI images, and the shortest LTD was measured for each tract. Postoperative morbidity and mortality information was collected from electronic medical records. The ipsilesional corticospinal tract LTD and left SLF LTD were significantly associated with the occurrence rate of total postoperative motor (P = .018) and language (P &lt; .001) deficits, respectively. The left SLF LTD wa...

Poor insight into illness is commonly associated with schizophrenia and has implications for the clinical outcome of the disease. A better understanding of the neurobiology of these insight deficits may help the development of new treatments targeting insight. Despite the importance of this issue, the neural correlates of insight deficits in schizophrenia remain poorly understood.

Objective: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. Method: T h e s u b j e c ts we r e n o n d emented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. Results: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. Conclusions: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.

Recent genetics research focusing on schizophrenia has led to candidate cognitive and neuroimaging variables as intermediate phenotypes or “endophenotype” markers for the illness. Among other stringent criteria, to be an endophenotype, a marker must demonstrate heritability. In an effort to explore the validity of a selection of cognitive and neuroimaging endophenotypes, the present study was designed to determine estimates of their heritability. One hundred fourteen subjects, including 27 with schizophrenia and 39 unaffected relatives from 23 multiplex schizophrenia families, participated in a comprehensive neuropsychological test battery and structural brain imaging with diffusion tensor imaging (DTI). Variables were selected if they previously have been demonstrated to show differences between people with schizophrenia and normal controls. Significant evidence of heritability was confirmed for overall cognitive function (“g”), as well as expressive and receptive language, verbal ...

This paper presents an immersive visualization tool that helps anatomists to establish a ground truth for brain white matter fiber bundles. Each step of a progressive anatomical dissection of human brain hemisphere is acquired using a high resolution 3D laser scanner and a photographic device. Each resulting surface is textured with a high resolution image and registered into a common 3D space using fiducial landmarks. Surfaces can be visualized using stereoscopic hardware and are interactively selectable. The tool allows the user to identify specific fiber bundle parts. Extracted fiber bundles are stacked together and rendered in stereoscopy with the corresponding MR volume. Surgeons have validated this tool for creating ground truth in medical imaging with the perspective of validating tractography algorithms.

Introduction: Diffusion tractography relies on complex mathematical models that provide anatomical information indirectly, and it needs to be validated. In humans, up to now, tractography has mainly been validated by qualitative comparison with data obtained from dissection. No quantitative comparison was possible because Magnetic Resonance Imaging (MRI) and dissection data are obtained in different reference spaces, and because fiber tracts are progressively destroyed by dissection. Here, we propose a novel method and software (FIBRASCAN) that allow accurate reconstruction of fiber tracts from dissection in MRI reference space. Method: Five human hemispheres, obtained from four formalin-fixed brains were prepared for Klingler's dissection, placed on a holder with fiducial markers, MR scanned, and then dissected to expose the main association tracts. During dissection, we performed iterative acquisitions of the surface and texture of the specimens using a laser scanner and two digital cameras. Each texture was projected onto the corresponding surface and the resulting set of textured surfaces was coregistered thanks to the fiducial holders. The identified association tracts were then interactively segmented on each textured surface and reconstructed from the pile of surface segments. Finally, the reconstructed tracts were coregistered onto ex vivo MRI space thanks to the fiducials. Each critical step of the process was assessed to measure the precision of the method. Results: We reconstructed six fiber tracts (long, anterior and posterior segments of the superior longitudinal fasciculus; Inferior fronto-occipital, Inferior longitudinal and uncinate fasciculi) from cadaveric dissection and ported them into ex vivo MRI reference space. The overall accuracy of the method was of the order of 1 mm: surface-to-surface registration = 0.138 mm (standard deviation (SD) = 0.058 mm), deformation of the specimen during dissection = 0.356 mm (SD = 0.231 mm), and coregistration surface-MRI = 0.6 mm (SD = 0.274 mm). The spatial resolution of the method (distance between two consecutive surface acquisitions) was 0.345 mm (SD = 0.115 mm). Conclusion: This paper presents the robustness of a novel method, FIBRASCAN, for accurate reconstruction of fiber tracts from dissection in the ex vivo MR reference space. This is a major step toward quantitative comparison of MR tractography with dissection results.

This paper presents the structural proof that the four hidden paths of the Christian English Qabalah are real, that they are categorically distinct from the twenty-two standard paths, and that their existence is confirmed by the very neuroscience that validates the standard architecture. The proof proceeds by contrast. The brain builds direct cortico-limbic white matter tracts for the posterior cortices (Netzach and Hod), connecting them to the hippocampus and amygdala (Yesod) through the parahippocampal cingulum and the ventral and dorsal visual processing streams. These are standard cortico-cortical paths: glutamatergic, representational, informationally rich. The brain deliberately does not build equivalent tracts for the frontal executive cortices (Geburah and Chesed), instead firewalling them from the limbic system behind the Salience Network’s gating architecture (Tiphareth). The medial forebrain bundle breaches this firewall from below through a fundamentally different class of neural infrastructure: subcortical monoaminergic neuromodulatory projections that change the executive’s operating state rather than carrying representational content. The hidden paths are not additional cortico-cortical paths of the same kind as the twenty-two. They are subcortical modulatory channels operating beneath the cortical architecture the Tree describes — the serpent beneath the Tree, confirmed by contrast with the standard paths that the posterior cortices possess and the frontal executive does not.

Patrick R. Nicolas' 2026 Substack article "Joint Embedding Predictive Architecture Unpacked" (Nicolas, 2026) provides a comprehensive, practitioner-oriented synthesis of the Joint Embedding Predictive Architecture (JEPA) framework originally proposed by Yann LeCun. This review anatomically dissects the article's structure, content, visual pedagogy, and theoretical fidelity. It evaluates the piece against the primary scientific literature,

En la última revisión de los criterios diagnósticos para esclerosis múltiple (EM) la imagen de resonancia magnética desplazó al análisis del líquido cefalorraquídeo (LCR). Los objetivos de este estudio fueron establecer el valor de corte del índice IgG entre pacientes con bandas oligoclonales (BOC) (+) y BOC (-), la prevalencia de BOC y evaluar la utilidad del índice IgG, Reibergrama (R) y BOC en pacientes con sospecha de EM. Se incluyeron 210 pacientes consecutivos, se determinó el índice IgG, R y BOC por isoelectroenfoque (IEE). Se accedió a los datos clínicos de 135 pacientes. Un índice IgG &gt;0,58 tuvo una sensibilidad=100% para la presencia de BOC en LCR. En pacientes con BOC (+) el índice IgG y el R fueron sensibles pero no específicos para EM. En pacientes con BOC (+) los patrones de IEE tipo 2 o 3 fueron los únicos asociados a EM y sólo en estos pacientes se observaron 9 o más BOC en LCR; la prevalencia de BOC con estos patrones fue de 82% para EM, 42% en el síndrome clínic...

Diffusion MRI (dMRI) is a powerful imaging modality that allows us to non-invasively examine the organization and integrity of fibrous tissue, particularly the brain's white matter. The result of a dMRI scan is a 3D image where each voxel contains a model that describes the local diffusion pattern of water molecules. The complicated nature and high dimensionality of these voxel-wise models make dMRI analysis especially challenging. The challenges increase when we look at dMRI scans from infants born prematurely. The smaller brain size for these infants, and the still-emerging brain structures these infants possess, increase the challenges involved in processing, analyzing, and interpreting dMRI scans. This thesis introduces four computational contributions in the area of dMRI analysis that attempt to address challenges exacerbated when imaging the preterm infant brain. Specifically, these four contributions are: (a) the first information content estimators for unaltered dMRI data, including a mutual information estimator for image registration; (b) a novel dMRI segmentation algorithm based on a cross-sectional piecewise constant image model; (c) the first global, closed-form probabilistic tractography algorithm, one where tracts compete for space in the brain; and (d) STEAM: the first patient-specific statistical abnormality mapping technique. In these four contributions, we model the dMRI data more accurately in order to improve the accuracy of dMRI analysis techniques, particularly in the presence of the small brain sizes and still-emerging brain structures seen in preterm infant dMRI. We further make the source code for these contributions publicly available to aid in the reproducibility of our research.

Background. Recovery of arm function after stroke is often incomplete. An improved understanding of brain structuremotor behavior relationships is needed for the development of novel and targeted rehabilitation interventions. Objective. To examine the relationship between skilled reach performance and the integrity of two putative white matter motor pathways, corticospinal tract and corpus callosum, after stroke. Methods. Eleven individuals with chronic stroke (poststroke duration, mean 62.5 ± 42.4 months) and mild motor impairment (upper extremity Fugl-Meyer score, mean 54.2 ± 7.6) reached to six targets presented at three distances and two directions. Fractional anisotropy (FA) obtained from diffusion tensor imaging was used to determine the structural integrity of the corticospinal tract and the corpus callosum. Results. Overall reach performance was decreased in the paretic arm compared with the nonparetic arm. While FA was decreased in the ipsilesional corticospinal tract, FA in the corticospinal tract did not correlate with variability in reach performance between individuals. Instead, FA in the premotor section of the corpus callosum correlated with reach performance; individuals with higher FA in premotor corpus callosum tended to reach faster with both the paretic and nonparetic arms. Conclusions. The structural connections between the two premotor and supplemental cortices that traverse the premotor corpus callosum may play an important role in supporting motor control and could become a target for interventions aimed at improved arm function in this population.

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43-68 years) and duration (1.7-22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features

nature publishing group IntroductIon: Objective biomarkers are needed to assess neuroprotective therapies after perinatal hypoxic-ischemic encephalopathy (hIe). We tested the hypothesis that, in infants who underwent therapeutic hypothermia after perinatal hIe, neurodevelopmental performance was predicted by fractional anisotropy (Fa) values in the white matter (WM) on early diffusion tensor imaging (DTI) as assessed by means of tract-based spatial statistics (TBss). Methods: We studied 43 term infants with hIe. Developmental assessments were carried out at a median (range) age of 24 (12-28) mo. results: as compared with infants with favorable outcomes, those with unfavorable outcomes had significantly lower Fa values (P < 0.05) in the centrum semiovale, corpus callosum (cc), anterior and posterior limbs of the internal capsule, external capsules, fornix, cingulum, cerebral peduncles, optic radiations, and inferior longitudinal fasciculus. In a second analysis in 32 assessable infants, the Griffiths Mental Development scales (Revised) (GMDs-R) showed a significant linear correlation (P < 0.05) between Fa values and developmental quotient (DQ) and all its component subscale scores. dIscussIon: DTI analyzed by TBss provides a qualified biomarker that can be used to assess the efficacy of additional neuroprotective therapies after hIe.

Aim-Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity. Methods-DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. Results-The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p<0.006 corrected for multiple comparisons). They also had lower fractional anisotropy values for the IFOF and higher radial diffusivity values for the left IFOF (p<0.006). Additionally, children with Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p<0.006). Significant correlations were noted between DTI parameters and some of the clinical assessment outcomes (e.g. language, socialization, cognition) for three of the temporal pathways (AF, UF, ILF; p<0.05). Interpretation-Changes in DTI parameters in individuals with Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in

Injurious mechanical ventilation causes white matter (WM) injury in preterm infants through inflammatory and haemodynamic pathways. The relative contribution of each of these pathways is not known. We hypothesised that in vivo magnetic resonance imaging (MRI) can detect WM brain injury resulting from mechanical ventilation 24 h after preterm delivery. Further we hypothesised that the combination of inflammatory and haemodynamic pathways, induced by umbilical cord occlusion (UCO) increases brain injury at 24 h. Fetuses at 124±2 days gestation were exposed, instrumented and either ventilated for 15 min using a high tidal-volume (V T ) injurious strategy with the umbilical cord intact (INJ; inflammatory pathway only), or occluded (INJ+UCO; inflammatory and haemodynamic pathway). The ventilation groups were compared to lambs that underwent surgery but were not ventilated (Sham), and lambs that did not undergo surgery (unoperated control; Cont). Fetuses were placed back in utero after the 15 min intervention and ewes recovered. Twenty-four hours later, lambs were delivered, placed on a protective ventilation strategy, and underwent MRI of the brain using structural, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) techniques. Absolute MRS concentrations of creatine and choline were significantly decreased in INJ +UCO compared to Cont lambs (P = 0.03, P = 0.009, respectively); no significant differences were detected between the INJ or Sham groups and the Cont group. Axial diffusivities in the internal capsule and frontal WM were lower in INJ and INJ+UCO compared to Cont lambs (P = 0.05, P = 0.04, respectively). Lambs in the INJ and INJ+UCO groups had lower

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn 2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn 2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn 2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatalthalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here.

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLEmts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in