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Annals of Clinical and Translational... May 2024To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo...
OBJECTIVE
To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI.
METHODS
In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex.
RESULTS
Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes.
INTERPRETATION
Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.
PubMed: 38725151
DOI: 10.1002/acn3.52026 -
Brain Sciences Apr 2024The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human... (Review)
Review
The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human primates. However, studies aiming to harmonize the definition of the cortical layers and borders of V1 across rodents and primates are very limited. This article attempts to identify and harmonize the molecular markers and connectional patterns that can consistently link corresponding cortical layers of V1 and borders across mammalian species and ages. V1 in primates has at least two additional and unique layers (L3b2 and L3c) and two sublayers of layer 4 (L4a and L4b) compared to rodent V1. In all species examined, layers 4 and 3b of V1 receive strong inputs from the (dorsal) lateral geniculate nucleus, and V1 is mostly surrounded by the secondary visual cortex except for one location where V1 directly abuts area prostriata. The borders of primate V1 can also be clearly identified at mid-gestational ages using gene markers. In rodents, a novel posteromedial extension of V1 is identified, which expresses V1 marker genes and receives strong inputs from the lateral geniculate nucleus. This V1 extension was labeled as the posterior retrosplenial cortex and medial secondary visual cortex in the literature and brain atlases. Layer 6 of the rodent and primate V1 originates corticothalamic projections to the lateral geniculate, lateral dorsal, and reticular thalamic nuclei and the lateroposterior-pulvinar complex with topographic organization. Finally, the direct geniculo-extrastriate (particularly the strong geniculo-prostriata) projections are probably major contributors to blindsight after V1 lesions. Taken together, compared to rodents, primates, and humans, V1 has at least two unique middle layers, while other layers are comparable across species and display conserved molecular markers and similar connections with the visual thalamus with only subtle differences.
PubMed: 38672021
DOI: 10.3390/brainsci14040372 -
Brain Communications 2024The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding...
The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.
PubMed: 38638150
DOI: 10.1093/braincomms/fcae117 -
JAACAP Open Dec 2023A growing body of literature has focused on the neural mechanisms of depression. Our goal was to conduct a systematic review on the white matter microstructural...
OBJECTIVE
A growing body of literature has focused on the neural mechanisms of depression. Our goal was to conduct a systematic review on the white matter microstructural differences in adolescents with depressive disorders vs adolescents without depressive disorders.
METHOD
We searched PubMed and PsycINFO for publications on August 3, 2022 (original search conducted in July 2021). The review was registered on PROSPERO (registration number: CRD42021268200), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Eligible studies were original research papers comparing diffusion tensor/spectrum imaging findings in adolescents with vs without depression (originally ages 12-19 years, later expanded to 11-21 years). Studies were excluded if they focused on depression exclusively in the context of another condition, used only dimensional depressive symptom assessment(s), or used the same dataset as another included publication.
RESULTS
The search yielded 575 unique records, of which 14 full-text papers were included (824 adolescents with depression and 686 without depression). The following white matter regions showed significant differences in fractional anisotropy in at least 3 studies: uncinate fasciculus, cingulum, anterior corona radiata, inferior fronto-occipital fasciculus, and corpus callosum (genu and body). Most studies reported decreased, rather than increased, fractional anisotropy in adolescents with depression. Limitations include the possibility for selective reporting bias and risk of imprecision, given the small sample sizes in some studies.
CONCLUSION
Our systematic review suggests aberrant white matter microstructure in limbic-cortical-striatal-thalamic circuits, and the corpus callosum, in adolescents with depression. Future research should focus on developmental trajectories in depression, identifying sources of heterogeneity and integrating findings across imaging modalities.
PubMed: 38576601
DOI: 10.1016/j.jaacop.2023.08.006 -
Research Square Mar 2024Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry...
Neuromodulation trials for PTSD have yielded mixed results, and the optimal neuroanatomical target remains unclear. We analyzed three datasets to study brain circuitry causally linked to PTSD in military Veterans. After penetrating traumatic brain injury (n=193), lesions that reduced probability of PTSD were preferentially connected to a circuit including the medial prefrontal cortex (mPFC), amygdala, and anterolateral temporal lobe (cross-validation p=0.01). In Veterans without lesions (n=180), PTSD was specifically associated with connectivity within this circuit (p<0.01). Connectivity change within this circuit correlated with PTSD improvement after transcranial magnetic stimulation (TMS) (n=20) (p<0.01), even though the circuit was not directly targeted. Finally, we directly targeted this circuit with fMRI-guided accelerated TMS, leading to rapid resolution of symptoms in a patient with severe lifelong PTSD. All results were independent of depression severity. This lesion-based PTSD circuit may serve as a neuromodulation target for Veterans with PTSD.
PubMed: 38562753
DOI: 10.21203/rs.3.rs-3132332/v1 -
Aging Mar 2024The transition to menopause is associated with various physiological changes, including alterations in brain structure and function. However, menopause-related...
The transition to menopause is associated with various physiological changes, including alterations in brain structure and function. However, menopause-related structural and functional changes are poorly understood. The purpose of this study was not only to compare the brain volume changes between premenopausal and postmenopausal women, but also to evaluate the functional connectivity between the targeted brain regions associated with structural atrophy in postmenopausal women. Each 21 premenopausal and postmenopausal women underwent magnetic resonance imaging (MRI). T1-weighted MRI and resting-state functional MRI data were used to compare the brain volume and seed-based functional connectivity, respectively. In statistical analysis, multivariate analysis of variance, with age and whole brain volume as covariates, was used to evaluate surface areas and subcortical volumes between the two groups. Postmenopausal women showed significantly smaller cortical surface, especially in the left medial orbitofrontal cortex (mOFC), right superior temporal cortex, and right lateral orbitofrontal cortex, compared to premenopausal women ( < 0.05, Bonferroni-corrected) as well as significantly decreased functional connectivity between the left mOFC and the right thalamus was observed ( < 0.005, Monte-Carlo corrected). Although postmenopausal women did not show volume atrophy in the right thalamus, the volume of the right pulvinar anterior, which is one of the distinguished thalamic subnuclei, was significantly decreased ( < 0.05, Bonferroni-corrected). Taken together, our findings suggest that diminished brain volume and functional connectivity may be linked to menopause-related symptoms caused by the lower sex hormone levels.
Topics: Humans; Female; Magnetic Resonance Imaging; Postmenopause; Brain; Thalamus; Atrophy
PubMed: 38526330
DOI: 10.18632/aging.205662 -
JAMA Psychiatry May 2024Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has significant potential as a novel treatment to reduce PTSD symptoms.
OBJECTIVE
To test whether active transcranial direct current stimulation (tDCS) plus virtual reality (VR) is superior to sham tDCS plus VR for warzone-related PTSD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind randomized clinical trial was conducted among US military veterans enrolled from April 2018 to May 2023 at a secondary care Department of Veterans Affairs hospital and included 1- and 3-month follow-up visits. Participants included US military veterans with chronic PTSD and warzone-related exposure, recruited via referral and advertisement. Patients in psychiatric treatment had to be on a stable regimen for at least 6 weeks to be eligible for enrollment. Data were analyzed from May to September 2023.
INTERVENTION
Participants were randomly assigned to receive 2-mA anodal tDCS or sham tDCS targeted to the ventromedial prefrontal cortex, during six 25-minute sessions of standardized warzone VR exposure, delivered over 2 to 3 weeks.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were self-reported PTSD symptoms, measured via the PTSD checklist for DSM-5 (PCL-5), alongside quality of life. Other outcomes included psychophysiological arousal, clinician-assessed PTSD, depression, and social/occupational function.
RESULTS
A total of 54 participants (mean [SD] age, 45.7 [10.5] years; 51 [94%] males) were assessed, including 26 in the active tDCS group and 28 in the sham tDCS group. Participants in the active tDCS group reported a superior reduction in self-reported PTSD symptom severity at 1 month (t = -2.27, P = .02; Cohen d = -0.82). There were no significant differences in quality of life between active and sham tDCS groups. Active tDCS significantly accelerated psychophysiological habituation to VR events between sessions compared with sham tDCS (F5,7689.8 = 4.65; P < .001). Adverse effects were consistent with the known safety profile of the corresponding interventions.
CONCLUSIONS AND RELEVANCE
These findings suggest that combined tDCS plus VR may be a promising strategy for PTSD reduction and underscore the innovative potential of these combined technologies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03372460.
Topics: Humans; Stress Disorders, Post-Traumatic; Transcranial Direct Current Stimulation; Male; Female; Double-Blind Method; Adult; Veterans; Middle Aged; Prefrontal Cortex; Virtual Reality Exposure Therapy; Virtual Reality
PubMed: 38446471
DOI: 10.1001/jamapsychiatry.2023.5661 -
Scientific Reports Feb 2024The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities....
The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities. Previous research suggests that non-invasive transcranial Alternating Current Stimulation (tACS) can moderately improve cognitive decline in older adults. However, non-declarative cognition has received relatively less attention. This study investigates whether repeated (16-day) bilateral theta-gamma cross-frequency tACS targeting the Dorsolateral Prefrontal Cortex (DLPFC) enhances non-declarative memory. Computerized cognitive training was applied alongside stimulation to control for the state-of-the-brain. The Alternating Serial Reaction Time (ASRT) task was employed to assess non-declarative functions such as visuomotor skill and probabilistic sequence learning. Results from 35 participants aged 55-82 indicated that active tACS led to more substantial improvements in visuomotor skills immediately after treatment, which persisted 3 months later, compared to sham tACS. Treatment benefit was more pronounced in older adults of younger age and those with pre-existing cognitive decline. However, neither intervention group exhibited modulation of probabilistic sequence learning. These results suggest that repeated theta-gamma tACS can selectively improve distinct non-declarative cognitive aspects when targeting the DLPFC. Our findings highlight the therapeutic potential of tACS in addressing deficits in learning and retaining general skills, which could have a positive impact on the quality of life for cognitively impaired older individuals by preserving independence in daily activities.
Topics: Humans; Aged; Transcranial Direct Current Stimulation; Quality of Life; Learning; Cognition; Brain
PubMed: 38418511
DOI: 10.1038/s41598-024-55125-2 -
Proceedings of the National Academy of... Mar 2024Music is powerful in conveying emotions and triggering affective brain mechanisms. Affective brain responses in previous studies were however rather inconsistent,...
Music is powerful in conveying emotions and triggering affective brain mechanisms. Affective brain responses in previous studies were however rather inconsistent, potentially because of the non-adaptive nature of recorded music used so far. Live music instead can be dynamic and adaptive and is often modulated in response to audience feedback to maximize emotional responses in listeners. Here, we introduce a setup for studying emotional responses to live music in a closed-loop neurofeedback setup. This setup linked live performances by musicians to neural processing in listeners, with listeners' amygdala activity was displayed to musicians in real time. Brain activity was measured using functional MRI, and especially amygdala activity was quantified in real time for the neurofeedback signal. Live pleasant and unpleasant piano music performed in response to amygdala neurofeedback from listeners was acoustically very different from comparable recorded music and elicited significantly higher and more consistent amygdala activity. Higher activity was also found in a broader neural network for emotion processing during live compared to recorded music. This finding included observations of the predominance for aversive coding in the ventral striatum while listening to unpleasant music, and involvement of the thalamic pulvinar nucleus, presumably for regulating attentional and cortical flow mechanisms. Live music also stimulated a dense functional neural network with the amygdala as a central node influencing other brain systems. Finally, only live music showed a strong and positive coupling between features of the musical performance and brain activity in listeners pointing to real-time and dynamic entrainment processes.
Topics: Music; Brain; Emotions; Amygdala; Affect; Magnetic Resonance Imaging; Auditory Perception
PubMed: 38408255
DOI: 10.1073/pnas.2316306121 -
Cureus Jan 2024Understanding the role of the pulvinar nucleus may be critical for guiding circuit-targeted neurosurgical intervention in some patients. In this report, a 33-year-old...
Understanding the role of the pulvinar nucleus may be critical for guiding circuit-targeted neurosurgical intervention in some patients. In this report, a 33-year-old female presented with focal onset occipital epilepsy with secondary generalization and with a previously radiated arteriovenous malformation within the right primary visual cortex. Phase II monitoring demonstrated the pulvinar nucleus was not involved in subclinical seizures restricted to the primary visual cortex, but it did become involved in clinical events with more extensive seizure spread into higher visual cortical regions. She underwent responsive neurostimulation (RNS) with implantation of leads within the primary visual cortex. This case demonstrates the late propagation of epileptic activity from the visual cortex to the pulvinar nucleus and illustrates the pulvinar nucleus' connections with higher-order visual areas.
PubMed: 38371112
DOI: 10.7759/cureus.52534