Search Results (98)

Background/Objectives: Advanced childhood cerebral X-linked adrenoleukodystrophy (cALD) is traditionally regarded as an irreversible terminal phase of neurodegeneration driven by inflammatory demyelination and axonal loss. Experimental evidence indicates that endogenous bioelectrical fields regulate central nervous system organisation, raising the possibility that functional network collapse in cALD may be biologically modifiable, even in the presence of persistent structural damage. This study examined whether longitudinal modulation of endogenous bioelectrical network organisation is associated with sustained clinical and neurophysiological stabilisation in advanced cALD. Methods: We performed a longitudinal observational analysis of two paediatric patients with advanced childhood cerebral X-linked adrenoleukodystrophy undergoing repeated neuroregenerative treatment cycles. Standardised scalp electroencephalography was recorded during spontaneous wakefulness and repeated over months under comparable vigilance conditions. Multimodal analysis included conventional EEG, quantitative EEG, independent component analysis, and standardised low-resolution electromagnetic tomography (sLORETA). Clinical function was assessed using validated measures of consciousness, swallowing, and voluntary motor behaviour. Results: Across patients, longitudinal recordings demonstrated sustained stabilisation of consciousness, swallowing, and voluntary motor function, accompanied by reproducible reorganisation of pathological brain rhythms. Delta and theta oscillations showed a consistent topographical redistribution from limbic–frontoinsular networks towards sensorimotor and parietal integrative cortices. These changes were observed across modalities and timepoints and are unlikely to reflect spontaneous fluctuation, delayed effects of haematopoietic stem cell transplantation, or state-dependent EEG variation. Conclusions: Advanced childhood cerebral X-linked adrenoleukodystrophy is associated with disorganisation of endogenous bioelectrical network activity. In this longitudinal analysis, large-scale network reorganisation was temporally associated with sustained clinical stabilisation, supporting a view of late-stage cALD as a dynamic disorder of network-level vulnerability, rather than a fixed terminal state. Full article

Mesial temporal lobe epilepsy (TLE) is the most common and severe form of focal epilepsy. This review examines the diverse mechanisms by which the GABAergic system contributes both to seizure generation and to protective processes that limit epileptogenesis and seizure progression in TLE. We focus on findings from established animal models of TLE as well as studies of surgically resected tissue from patients who had undergone therapeutic intervention. Experimental models include sustained electrical stimulation of the perforant path, as well as the kainic acid (KA) and Li-pilocarpine models. Although these paradigms induce status epilepticus (SE) through distinct mechanisms, they ultimately converge on prolonged excitation of hippocampal CA3 pyramidal neurons and interconnected regions of the hippocampus and broader limbic network. In response to epileptic seizures, GABA synthesis is enhanced, as evidenced by the marked upregulation of the GABA-synthesizing enzymes GAD65 and GAD67, along with their ectopic expression in glutamatergic mossy fibers of the hippocampus. Shortly after acute seizures, a transient expression of the embryonic GAD67 splice variant, GAD25, is observed, although its functional significance remains unclear. At the receptor level, animal models of TLE show upregulation of GABA_A receptor subunits α2, α4, β3, and γ2, accompanied by downregulation of α5 and δ subunits, suggesting reduced tonic inhibition. In contrast, hippocampal tissue from patients with TLE exhibits pronounced upregulation of α5 and δ subunits, indicative of enhanced extrasynaptic tonic inhibition. Similarly, whereas GABA_A receptor subunits are mildly downregulated in animal models, they are consistently upregulated across hippocampal subfields in human TLE, pointing toward strengthened GABAergic inhibition. Conversely, genetic variants of GABA_A receptor subunits and autoantibodies targeting these receptors can contribute to the etiology of epilepsy, often with onset in childhood. Moreover, degeneration or functional silencing of specific GABAergic interneuron populations—such as parvalbumin-positive neurons in the subiculum—can induce epilepsy in rodent models and is likewise associated with TLE in humans. Full article

Over the past four decades, tinnitus research has grown into a highly interdisciplinary field spanning auditory science, neuroscience, psychology, and clinical medicine. Yet how knowledge across subfields has been inherited, diversified, and integrated over time still lacks traceable structural evidence. To address this gap and move beyond frequency-oriented reviews and bibliometric studies that mainly report “hot topics” and prolific contributors, the present study reconstructs the intellectual evolution of tinnitus research (1984–2025) using citation-network-based main path analysis (MPA). From the Web of Science Core Collection, 6584 records were initially retrieved, of which 6354 formed a mutually linked core citation network (96.5%), indicating high coverage and analyzability. SPLC (Search Path Link Count)–weighted MPA was applied to extract global and key-route main paths capturing dominant knowledge trajectories and major branches. Cluster and co-word analyses were then integrated to delineate seven evolutionary stages and five major thematic clusters. This framework identifies bridging works and turning points and reveals how emerging lines—neuromodulation, implant-related treatments, and digital/telehealth CBT—branch from and later converge with established neurobiological and psychological pathways rather than appearing in isolation. Overall, the field has progressed from early psychoacoustics and spontaneous otoacoustic emissions through cochlear-injury plasticity, central gain, and limbic–auditory network models, and most recently toward mechanism-oriented diagnostics, individualized assessment, and targeted interventions. Full article

Background: Addictive disorders are characterized by the dysregulation of neural circuits involved in reward processing, salience attribution, emotional regulation, and cognitive control. Traditional neuroimaging paradigms based on static or two-dimensional stimuli show limited ecological validity and may fail to capture the contextual complexity of real-world addictive triggers. Immersive virtual reality (VR) offers a novel approach to simulate realistic, multisensory environments capable of eliciting craving and emotional responses. Although several reviews have examined VR in addictive disorders, most combined immersive and non-immersive tools and did not restrict inclusion to studies with brain-based outcomes. Methods: This systematic review with narrative synthesis was conducted in PubMed/MEDLINE and APA PsycINFO for studies published up to 30 December 2025. This systematic review followed PRISMA 2020 and was prospectively registered in PROSPERO; due to heterogeneity, findings were synthesized narratively. Eligible studies included human participants with substance-related or behavioral addictions and employed immersive VR paradigms (e.g., head-mounted display–based environments) combined with neuroimaging or neurophysiological measures (EEG, fMRI, fNIRS, PET, or DTI). Risk of bias was assessed using ROB-2 or ROBINS-I, and overall certainty of evidence was evaluated with the GRADE framework. Results: Ten studies met the inclusion criteria, encompassing over 1450 participants with alcohol, nicotine, methamphetamine, opioid use disorders, and internet gaming disorder. Immersive VR was associated with craving-related neural responses across modalities, involving prefrontal, insular, limbic, and striatal networks. EEG studies reported spectral power changes associated with craving and attentional salience, while fMRI, fNIRS, and PET studies demonstrated activation and modulation of executive control and reward-related circuits. Preliminary longitudinal and interventional studies indicate that repeated VR exposure may induce neurobiological changes consistent with therapeutic modulation. Conclusions: Immersive VR combined with neuroimaging supports the use of immersive VR as an ecologically grounded framework to probe addiction-related brain circuits; however, larger trials and standardized reporting are needed to strengthen clinical translation. Future studies should prioritize adequately powered randomized designs, harmonized VR cue-reactivity paradigms, and transparent neuroimaging reporting to enable reproducibility and cumulative inference. Full article

Mild traumatic brain injury (mTBI) is typically associated with transient cognitive disturbance, particularly involving attention and new learning, with most patients demonstrating full recovery within weeks. Memory impairment in uncomplicated mTBI generally reflects reversible neurometabolic dysfunction and is limited to a brief period of post-traumatic amnesia and restricted retrograde loss surrounding the injury. However, a subset of patients develop persistent and disproportionate autobiographical memory disturbance that exceeds expected neuroanatomical limits and lacks structural correlates on neuroimaging. In rare but clinically challenging cases, this presentation may resemble extensive retrograde or identity-related amnesia. This review examines functional (dissociative) amnesia emerging after mTBI and proposes that concussion may act as a gateway condition facilitating the development of Functional Cognitive Disorder (FCD) in vulnerable individuals. We differentiate expected post-traumatic memory patterns from atypical selective impairment of autobiographical retrieval and clarify how distinct memory systems—episodic, autobiographical, semantic, and procedural—are differentially affected. We expand the two-hit hypothesis by integrating contemporary neurobiological evidence. The first hit comprises concussion-induced neurometabolic disturbance, glial activation, oxidative imbalance, and transient fronto-limbic dysregulation. The second hit may involve psychological stress, identity threat, maladaptive metacognitive processes, or persistent neuroinflammatory signalling, collectively resulting in functional inhibition of autobiographical memory retrieval despite preserved memory storage. Functional amnesia is conceptualised as a severe phenotype within the spectrum of functional cognitive disorder. We introduce a structured clinician-administered interview (SIFRA) to operationalise diagnostic features and support systematic assessment. This integrative framework reconciles neurological vulnerability with functional network dysregulation and provides a coherent basis for diagnosis and multidisciplinary management of persistent memory disturbance after mTBI. Full article

Background and Objective: Adolescent bipolar disorder (BD) has substantial symptom overlaps with other psychiatric disorders. Identifying its distinctive candidate neuroimaging markers may be helpful for exploratory early differentiation and to inform future translational studies after independent validation. Methods: This cross-sectional study enrolled adolescents with BD and age- and sex-matched healthy controls. Assessments included clinical/behavioral scales and an emotional Go/NoGo task-based fMRI (Go trials require a response; NoGo trials require response inhibition) acquired across three mood states (depression, mania, and remission) and matched controls. We applied several conventional machine learning classifiers to task-fMRI data to classify BD versus healthy controls and to identify the most relevant neuroimaging predictors. Results: A total of 43 adolescents with BD (15 in remission, 11 with depression, and 17 with mania) and 43 matched healthy controls were included. Under the Go − NoGo condition, activation-derived features in the remission state showed the strongest discrimination, with RF achieving the best performance (accuracy = 94.29%, AUC = 98.57%). These findings suggest that task-evoked functional alterations may remain detectable during remission. In addition, activation patterns in regions within the limbic system, prefrontal cortex, and default mode network were significantly correlated with clinical scales and behavioral measures implicating these regions in emotion regulation and cognitive functioning in adolescents with BD. Conclusions: This study showed that adolescents with BD during remission without manic and depressive symptoms may still have aberrant neural activity in the limbic system, prefrontal cortex, and default mode network, which may serve as a potential candidate neuroimaging signature of adolescent BD. Full article

Bipolar affective disorder (BD) is a severe mental illness characterized by recurrent episodes of mania, hypomania, and depression, accompanied by progressive neurobiological changes that go beyond the classical concepts of neurotransmitter dysregulation. Increasing evidence points to the key role of the interaction between inflammatory processes, mitochondrial dysfunction, and disturbances within neural networks in the pathogenesis, course, and treatment response of BD. Neuroinflammatory processes, including elevated levels of pro-inflammatory cytokines, chemokines, and microglial activation, are consistently reported in patients with BD and linked to cognitive impairment, accelerated neuroprogression, and treatment resistance. At the same time, mitochondrial abnormalities—such as impaired oxidative phosphorylation, excessive production of reactive oxygen species, and disturbances in calcium homeostasis—contribute to oxidative stress, synaptic dysfunction, and increased neuronal vulnerability, forming the biological substrate of mood instability. Findings from neuroimaging studies provide consistent evidence of structural and functional alterations within the cortico-limbic networks regulating emotions, including the prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus. Importantly, a growing number of studies demonstrate correlations between neuroimaging changes and inflammatory and metabolic biomarkers, making it possible to link molecular pathology with dysfunctions at the level of neural networks. The use of multimodal methods—encompassing structural and functional magnetic resonance imaging, spectroscopy, and molecular analyses—allows for a more precise explanation of these complex interactions and the identification of biomarkers of clinical states, progression, and treatment response. This review synthesizes current knowledge on the molecular and neuroimaging correlates of BD, emphasizing the interdependence of inflammatory processes, mitochondrial function, and neural networks. The integration of molecular biomarkers with imaging-based phenotyping opens new perspectives for precision medicine in BD. Full article

Dogs show exceptional olfactory sensitivity and are widely used in medical, rescue, military, and forensic applications, yet the determinants of individual and breed-level scent-work performance remain incompletely characterized. This review integrates evidence from the anatomy and physiology of the canine olfactory organ, neurobiological mechanisms of odor transduction and coding, and links between olfaction, memory, and emotion, alongside molecular genetics, evolution, domestication, and selective breeding. We synthesize findings indicating that complex nasal turbinates and specialized airflow patterns enhance odorant capture, while olfactory bulb circuitry and downstream connections to limbic and frontal networks support discrimination, learning, and affective modulation. Comparative and breed-focused studies suggest that skull morphology and breeding priorities can alter olfactory capacity, with shortened nasal anatomy associated with reduced functional potential in some lines. In applied contexts, detection success is strongly shaped by behavioral traits such as motivation, persistence, independence, and reward value, as well as by physical condition and environmental stressors that can impair search efficiency. Emerging literature further suggests that the gastrointestinal and upper airway microbiome, together with diet, housing, temperature, and workload, may influence sensory and cognitive readiness, although direct causal links to detection outcomes remain limited. Overall, canine olfactory performance reflects interactions among genetic–anatomical capacity, neurobehavioral factors, and environment, underscoring the value of standardized selection, training, welfare management, and future integrative research. Full article

Background/Objectives: In recent years, MRI-based diffusion-weighted tractography techniques have uncovered additional white matter pathways that have significant roles in language processing and production. In this review, we aim to outline the major language centers of the brain and major language pathways along with association tracts that serve dual roles in both the language and limbic systems. According to the current dual-stream model of language processing, the brain’s language network is organized into a dorsal stream, responsible for mapping sound to articulation, and a ventral stream, which maps sound to meaning. Materials and Methods: The literature cited in this manuscript was identified through targeted searches of the PubMed database. Priority was given to peer-reviewed human studies, including original neuroimaging, cadaveric validation, and intraoperative stimulation studies. Non-peer-reviewed sources and publications lacking clear anatomical or functional correlation to language pathways were excluded. Results: Advances in functional MRI and diffusion weighted imaging techniques have revealed a more interconnected network, expanding our understanding beyond the classical dual-stream model of language processing. The Kamali limbic model proposed distinct ventral and dorsal limbic networks. Notably, several fiber pathways within the ventral limbic network may subserve both language and limbic functions. The association tracts with dual limbic-language functions form a critical basis for understanding the pathophysiology of language disorders accompanied by cognitive and emotional comorbidities observed in dyslexia, speech apraxia, aphasia, autism spectrum disorder, schizophrenia and post-traumatic stress disorder. Conclusions: Visualizing the language center and interconnected dual language and limbic fiber tracts highlights the importance of integrating language, executive function, and emotion in developing disease models and designing effective, targeted treatments for patients. Full article

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, people living with all three conditions often struggle with mood issues like depression and anxiety, which can originate from both the burden of illness and changes in brain biology. We studied 61 patients (CD, n = 30; BSP, n = 9; HFS, n = 22) and assessed depression and anxiety before and three weeks after botulinum neurotoxin type A (BoNT-A) therapy, considering injection site and dose. BoNT-A significantly reduced depressive and anxiety symptoms across all groups, regardless of disease type, dose, or glabellar injection. These psychiatric improvements were not associated with the degree of motor symptom reduction, suggesting a partially independent mechanism of mood modulation. Our findings indicate that BoNT-A’s mood benefits may extend beyond local motor effects, possibly involving broader sensorimotor-limbic interactions. These results highlight the therapeutic potential of BoNT-A for addressing non-motor symptoms in both dystonic and non-dystonic hyperkinetic disorders. Future studies employing imaging and neurophysiological methods are necessary to explain the neural pathways underlying these effects. Full article

Obesity is a systemic metabolic disorder characterized by chronic low-grade inflammation and insulin resistance, with growing evidence indicating that the brain represents a primary and particularly vulnerable target organ. Beyond peripheral metabolic consequences, obesity induces region-specific structural, functional, and biochemical alterations within the central nervous system, contributing to cognitive impairment, dysregulated energy homeostasis, and increased susceptibility to neurodegenerative diseases. This narrative review examines key neurometabolic and neuroinflammatory mechanisms underlying obesity-related brain vulnerability, including downstream neuroinflammation, impaired insulin signaling, mitochondrial dysfunction, oxidative stress, blood–brain barrier disruption, and impaired brain clearance mechanisms. These processes preferentially affect frontal and limbic networks involved in executive control, reward processing, salience detection, and appetite regulation. Advanced neuroimaging has substantially refined our understanding of these mechanisms. Magnetic resonance spectroscopy provides unique in vivo insight into early neurometabolic alterations that may precede irreversible structural damage and is complemented by diffusion imaging, volumetric MRI, functional MRI, cerebral perfusion imaging, and positron emission tomography. Together, these complementary modalities reveal microstructural, network-level, structural, hemodynamic, and molecular alterations associated with obesity-related brain vulnerability and support the concept that such brain dysfunction is dynamic and potentially modifiable. Integrating neurometabolic and multimodal neuroimaging biomarkers with metabolic and clinical profiling may improve early risk stratification and guide preventive and therapeutic strategies aimed at preserving long-term brain health in obesity. Full article

Diffusion tensor imaging (DTI) tractography is routinely employed in neurosurgical planning; however, the prognostic significance of quantitative DTI metrics for postoperative functional outcomes remains unclear. We conducted a PRISMA-informed systematic review of PubMed (January 2005–1 December 2025), supplemented by additional indexed sources, to synthesize the evidence on quantitative DTI measures associated with postoperative motor, language, and cognitive outcomes following intracranial surgery. Thirty-seven studies were included, primarily single-center studies, and predominantly focused on glioma surgery. Motor outcomes exhibited the most consistent associations, with reduced corticospinal tract integrity and adverse postoperative diffusion changes correlating with muscle weakness and poorer recovery. Recovery from supplementary motor area syndrome was associated with interhemispheric callosal connectivity, with greater disconnection predicting a prolonged symptom duration. Language outcomes demonstrated reproducible structure–function relationships: higher preoperative integrity of the dorsal language pathways was associated with milder postoperative aphasia and better recovery, whereas postoperative tract disruption and diffusivity changes predicted persistent naming and fluency deficits, and ventral pathway alterations were specifically linked to lexico-semantic impairment. In epilepsy surgery, language performance correlated with contralateral and distributed network diffusion changes, consistent with reorganization. Evidence for cognition and gait outcomes was limited and mainly involved the association, limbic, and callosal pathways. Overall, quantitative DTI provides clinically relevant markers of tract and network disruption and postoperative remodeling; however, methodological heterogeneity and limited external validation currently preclude universal prognostic thresholds. Full article

This essay provides a neurobiological and neuroanatomical analysis of how the recently published Walla Emotion Model, with its neurobiologically grounded definitions, elucidates the evolutionary origin of affective processing from the sense of olfaction. The analysis first deconstructs the model’s hierarchical framework, which distinguishes between rapid, non-conscious affective processing (neural activity coding for valence of stimuli), conscious, subjective feelings, and observable, communicative emotions. It then details the unique neuroanatomical pathway of the olfactory system, highlighting its most direct, subcortical connections to the limbic system (only two synapses) (shared subcortical network between olfaction and affection). The core argument presented is that this emotion model’s definition of affective processing as being distinct from an emotion is a direct conceptual reflection of the ancient, hardwired, and survival-oriented function of olfaction. This link is substantiated by empirical evidence from studies on sniffing behavior, startle reflex modulation, and non-conscious physiological responses, all of which provide empirical evidence for a non-conscious, non-cognitive evaluation of olfactory stimuli. First, this essay concludes that a clear distinction between affective processing, feelings, and emotions offers a coherent framework that has the potential to resolve long-standing terminological ambiguities in the affective science. Second, it also aims at providing a paradigm for understanding the foundational role of a specific sensory modality in the evolution of our most primitive and yet so evident and impactful affective responses serving the adaptation of produced behavior in humans. Finally, some ideas for broader implications are mentioned. Full article

Religious experiences represent a universal and timeless phenomenon that has accompanied humanity since its origins. In recent decades, neuroscience has explored the relationship between temporal lobe epilepsy (TLE) and hyperreligiosity phenomena, describing sudden convictions, states of ecstasy, and spiritual conversions associated with epileptic seizures. This article offers a narrative review of the literature on the relationship between epilepsy and religion, including its clinical manifestations (ictal, postictal, and interictal) and the main neurobiological models proposed to explain it, such as the limbic marker hypothesis and theory of mind (ToM). The possible role of the uncinate fasciculus as an integrative pathway between temporal and limbic regions is also explored, based on recent neuroimaging studies. Finally, we present an illustrative clinical case of a patient with meningioma and TLE associated with episodes of intense religious conviction, in whom a structural alteration of the right uncinate fasciculus was observed. This case reinforces the relevance of considering both neuronal networks and white matter tracts in the study of religious experiences, while underscoring the need for broader and more systematic studies to confirm these findings. Full article

Tourette syndrome (TS), or Tourette’s, is a tic disorder (TD) belonging to a group of neuropsychiatric conditions marked by recurrent motor movements or vocalizations known as tics. TD, including TS, typically begins in childhood between 4 and 18 years of age and affects approximately 3% of children and adolescents. The etiology and pathogenesis of TD are multifactorial, involving genetic, immunologic, psychological, and environmental factors. Evidence suggests that neurotransmitter dysregulation, particularly within the cortical dopaminergic networks of the basal ganglia and limbic system, which support motor control and cognition, may be involved in the development of TD. Nutritional factors may modulate TD through various mechanisms, including effects on neurotransmitter synthesis and metabolism, neurodevelopment, neural architecture, and neuroimmune activity. This review integrates current evidence on the roles of vitamins D, B6, and A, as well as iron, magnesium, zinc, and copper, in TD. For each micronutrient, its physiological and neurobiological functions are discussed, along with possible mechanistic links to TD pathophysiology. Additionally, we summarize the impact of nutrient deficiencies and assess available evidence regarding their potential therapeutic potential role in TD management. Overall, this synthesis highlights how nutritional status may influence TD onset and symptom severity, suggesting that nutrient-based interventions could potentially serve as valuable adjunctive strategies in treatment. Full article