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Brain Sciences Apr 2024Considering the advantages of brain stimulation techniques in detecting the role of different areas of the brain in human sensorimotor behaviors, we used anodal...
Considering the advantages of brain stimulation techniques in detecting the role of different areas of the brain in human sensorimotor behaviors, we used anodal transcranial direct-current stimulation (a-tDCS) over three different brain sites of the frontoparietal cortex (FPC) in healthy participants to elucidate the role of these three brain areas of the FPC on reaction time (RT) during a sequential visual isometric pinch task (SVIPT). We also aimed to assess if the stimulation of these cortical sites affects the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: (1) left primary motor cortex (M1), (2) left dorsolateral prefrontal cortex (DLPFC), (3) left posterior parietal cortex (PPC), and (4) sham. A-tDCS (0.3 mA, 20 min) was applied concurrently with the SVIPT, in which the participants precisely controlled their forces to reach seven different target forces from 10 to 40% of the maximum voluntary contraction (MVC) presented on a computer screen with the right dominant hand. Four test blocks were randomly performed at the baseline and 15 min after the intervention, including sequence and random blocks with either hand. Our results showed significant elongations in the ratio of RTs between the M1 and sham groups in the sequence blocks of both the right-trained and left-untrained hands. No significant differences were found between the DLPFC and sham groups and the PPC and sham groups in RT measurements within the SVIPT. Our findings suggest that RT improvement within implicit learning of an SVIPT is not mediated by single-session a-tDCS over M1, DLPFC, or PPC. Further research is needed to understand the optimal characteristics of tDCS and stimulation sites to modulate reaction time in a precision control task such as an SVIPT.
PubMed: 38672057
DOI: 10.3390/brainsci14040408 -
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 -
Psychoradiology 2023Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain...
BACKGROUND
Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.
OBJECTIVE
To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.
METHODS
Twenty-five first-episode, treatment-naive adolescents with MDD and 19 healthy controls (HCs) underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests. Single-subject morphological brain networks were constructed separately based on cortical thickness, fractal dimension, gyrification index, and sulcus depth, and topologically characterized by graph-based approaches. Between-group differences were inferred by permutation testing. For significant alterations, partial correlations were used to examine their associations with clinical and neuropsychological variables in the patients. Finally, a support vector machine was used to classify the patients from controls.
RESULTS
Compared with the HCs, the patients exhibited topological alterations only in cortical thickness-based networks characterized by higher nodal centralities in parietal (left primary sensory cortex) but lower nodal centralities in temporal (left parabelt complex, right perirhinal ectorhinal cortex, right area PHT and right ventral visual complex) regions. Moreover, decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients. These results were largely reproducible for binary and weighted network analyses. Finally, topological properties of the cortical thickness-based networks were able to distinguish the MDD adolescents from HCs with 87.6% accuracy.
CONCLUSION
Adolescent MDD is associated with disrupted topological organization of morphological brain networks, and the disruptions provide potential biomarkers for diagnosing and monitoring the disease.
PubMed: 38666133
DOI: 10.1093/psyrad/kkad017 -
Ophthalmology. Retina Apr 2024To investigate the influence of vitreous cortex remnants (VCRs) removal on normal retinal anatomy in eyes with rhegmatogenous retinal detachment (RRD).
PURPOSE
To investigate the influence of vitreous cortex remnants (VCRs) removal on normal retinal anatomy in eyes with rhegmatogenous retinal detachment (RRD).
DESIGN
Prospective cohort study.
SUBJECTS
Patients with primary RRD operated with pars plana vitrectomy (PPV).
METHODS
Blue fundus autofluorescence and spectral-domain OCT were obtained preoperatively, and at 1 and 6 months after operation.
MAIN OUTCOME MEASURES
Primary outcomes: rate of retinal displacement and outer retinal folds (ORFs) at 1 month after operation.
SECONDARY OUTCOMES
continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ), and the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 6 months after operation.
RESULTS
One hundred three eyes were included. Intraoperatively, peripheral VCRs (pVCRs) were found in 42 eyes (40.8%) and successfully peeled off from ≥2 quadrants in 37 eyes. Macular VCRs (mVCRs) were detected in 37 (35.9%) and successfully peeled off in 29 eyes. At the end of operation 44.7% and 55.3% of the eyes were tamponaded with 20% sulfur hexafluoride gas and silicone oil 1000 centistokes, respectively. The only variable significantly associated with displacement was the use of gas tamponade versus silicone oil (P = 0.001), whereas no significant association was found between retinal displacement and pVCRs (P = 0.58) or number of quadrants from which pVCRs were peeled off (P = 0.39). At 1 month postoperatively, ORFs were globally detected in 24 eyes (23.3%). Regression analysis showed a direct correlation between ORFs and the intraoperative detection of mVCRs (P = 0.02) and an indirect correlation between ORFs and mVCRs peeling (P = 0.004). Macular VCRs peeling did not influence the continuity of ELM and EZ at the 6-month follow-up (FU). Intraoperative absence of mVCRs (P = 0.0016) and peeling of mVCRs (P = 0.003) were associated with logMAR BCVA ≤0.3 at the 6-month FU.
CONCLUSIONS
Peeling of pVCRs did not seem to influence the rate of retinal displacement, whereas peeling of mVCRs was associated with a reduced risk of developing ORFs without detrimental effect on the continuity of ELM/EZ at 6-month FU. The patients without mVCRs detected intraoperatively, or who underwent mVCRs peeling during operation, showed a significantly better visual acuity at the 6-month FU.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
PubMed: 38657953
DOI: 10.1016/j.oret.2024.04.015 -
Nature Communications Apr 2024Brightness illusions are a powerful tool in studying vision, yet their neural correlates are poorly understood. Based on a human paradigm, we presented illusory drifting...
Brightness illusions are a powerful tool in studying vision, yet their neural correlates are poorly understood. Based on a human paradigm, we presented illusory drifting gratings to mice. Primary visual cortex (V1) neurons responded to illusory gratings, matching their direction selectivity for real gratings, and they tracked the spatial phase offset between illusory and real gratings. Illusion responses were delayed compared to real gratings, in line with the theory that processing illusions requires feedback from higher visual areas (HVAs). We provide support for this theory by showing a reduced V1 response to illusions, but not real gratings, following HVAs optogenetic inhibition. Finally, we used the pupil response (PR) as an indirect perceptual report and showed that the mouse PR matches the human PR to perceived luminance changes. Our findings resolve debates over whether V1 neurons are involved in processing illusions and highlight the involvement of feedback from HVAs.
Topics: Animals; Neurons; Primary Visual Cortex; Mice; Photic Stimulation; Male; Humans; Optogenetics; Female; Visual Perception; Illusions; Optical Illusions; Mice, Inbred C57BL; Pupil; Visual Cortex
PubMed: 38653975
DOI: 10.1038/s41467-024-46885-6 -
Frontiers in Neuroanatomy 2024Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in...
Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 with anterograde and retrograde viral tracers. We found two types of local horizontal connections: short ones that were tangentially limited to the representation of the point image, and long ones which reached beyond the receptive field center, deep into its surround. The long connections were patchy and terminated preferentially in M2 muscarinic acetylcholine receptor-negative (M2-) interpatches. Anterogradely labeled inputs overlapped in M2-interpatches with apical dendrites of retrogradely labeled L2/3 and L5 cells, forming module-selective loops between topographically distant locations. Previous work showed that L1 of M2-interpatches receive inputs from the lateral posterior thalamic nucleus (LP) and from a feedback network from areas of the medial dorsal stream, including the secondary motor cortex. Together, these findings suggest that interactions in M2-interpatches play a role in processing visual inputs produced by object-and self-motion.
PubMed: 38650594
DOI: 10.3389/fnana.2024.1364675 -
Human Brain Mapping Apr 2024Functional gradient (FG) analysis represents an increasingly popular methodological perspective for investigating brain hierarchical organization but whether and how...
Functional gradient (FG) analysis represents an increasingly popular methodological perspective for investigating brain hierarchical organization but whether and how network hierarchy changes concomitant with functional connectivity alterations in multiple sclerosis (MS) has remained elusive. Here, we analyzed FG components to uncover possible alterations in cortical hierarchy using resting-state functional MRI (rs-fMRI) data acquired in 122 MS patients and 97 healthy control (HC) subjects. Cortical hierarchy was assessed by deriving regional FG scores from rs-fMRI connectivity matrices using a functional parcellation of the cerebral cortex. The FG analysis identified a primary (visual-to-sensorimotor) and a secondary (sensory-to-transmodal) component. Results showed a significant alteration in cortical hierarchy as indexed by regional changes in FG scores in MS patients within the sensorimotor network and a compression (i.e., a reduced standard deviation across all cortical parcels) of the sensory-transmodal gradient axis, suggesting disrupted segregation between sensory and cognitive processing. Moreover, FG scores within limbic and default mode networks were significantly correlated ( , p < .005 after Bonferroni correction for both) with the symbol digit modality test (SDMT) score, a measure of information processing speed commonly used in MS neuropsychological assessments. Finally, leveraging supervised machine learning, we tested the predictive value of network-level FG features, highlighting the prominent role of the FG scores within the default mode network in the accurate prediction of SDMT scores in MS patients (average mean absolute error of 1.22 ± 0.07 points on a hold-out set of 24 patients). Our work provides a comprehensive evaluation of FG alterations in MS, shedding light on the hierarchical organization of the MS brain and suggesting that FG connectivity analysis can be regarded as a valuable approach in rs-fMRI studies across different MS populations.
Topics: Humans; Male; Female; Adult; Magnetic Resonance Imaging; Cerebral Cortex; Middle Aged; Nerve Net; Connectome; Multiple Sclerosis; Default Mode Network
PubMed: 38647001
DOI: 10.1002/hbm.26678 -
MedRxiv : the Preprint Server For... Apr 2024Mutations in the gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In...
Mutations in the gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is the strongest pathological correlate of cognitive decline. Recently, PET imaging with synaptic tracers revealed clinically relevant loss of synapses in primary tauopathies; however, the molecular mechanisms leading to synapse degeneration in primary tauopathies remain largely unknown. In this study, we examined post-mortem brain tissue from people who died with frontotemporal dementia with tau pathology (FTDtau) caused by the intronic exon 10+16 mutation, which increases splice variants containing exon 10 resulting in higher levels of tau with four microtubule binding domains. We used RNA sequencing and histopathology to examine temporal cortex and visual cortex, to look for molecular phenotypes compared to age, sex, and RNA integrity matched participants who died without neurological disease (n=12 per group). Bulk tissue RNA sequencing reveals substantial downregulation of gene expression associated with synaptic function. Upregulated biological pathways in human 10+16 brain included those involved in transcriptional regulation, DNA damage response, and neuroinflammation. Histopathology confirmed increased pathological tau accumulation in FTDtau cortex as well as a loss of presynaptic protein staining, and region-specific increased colocalization of phospho-tau with synapses in temporal cortex. Our data indicate that synaptic pathology likely contributes to pathogenesis in FTDtau caused by the 10+16 mutation.
PubMed: 38645146
DOI: 10.1101/2024.04.09.24305501 -
BioRxiv : the Preprint Server For... Jun 2024Across all domains of brain stimulation (neuromodulation), conventional analysis of neuron activation involves two discrete steps: i) prediction of macroscopic electric...
Across all domains of brain stimulation (neuromodulation), conventional analysis of neuron activation involves two discrete steps: i) prediction of macroscopic electric field, ignoring presence of cells and; ii) prediction of cell activation from tissue electric fields. The first step assumes that current flow is not distorted by the dense tortuous network of cell structures. The deficiencies of this assumption have long been recognized, but - except for trivial geometries - ignored, because it presented intractable computation hurdles. This study introduces a novel approach for analyzing electric fields within a microscopically realistic brain volume. Our pipeline overcomes the technical intractability that prevented such analysis while also showing significant implications for brain stimulation. Contrary to the standard finite element method (FEM), we suggest using a nested iterative boundary element method (BEM) coupled with the fast multipole method (FMM). This approach allows for solving problems with multiple length scales more efficiently. A target application is a subvolume of the L2/3 P36 mouse primary visual cortex containing approximately 400 detailed densely packed neuronal cells at a resolution of 100 nm, which is obtained from scanning electron microscopy data. Our immediate result is a reduction of the stimulation field strength necessary for neuron activation by a factor of 0.85-0.55 (by 15%-45%) as compared to macroscopic predictions. This is in line with modern experimental data stating that existing macroscopic theories substantially overestimate electric field levels necessary for brain stimulation.
PubMed: 38645100
DOI: 10.1101/2024.04.04.588004 -
BioRxiv : the Preprint Server For... Apr 2024Neurons in primary visual cortex integrate sensory input with signals reflecting the animal's internal state to support flexible behavior. Internal variables, such as...
Neurons in primary visual cortex integrate sensory input with signals reflecting the animal's internal state to support flexible behavior. Internal variables, such as expectation, attention, or current goals, are imposed in a top-down manner via extensive feedback projections from higher-order areas. We optogenetically activated a high-order visual area, area 21a, in the lightly anesthetized cat (OptoTD), while recording from neuronal populations in V1. OptoTD induced strong, up to several fold, changes in gamma-band synchronization together with much smaller changes in firing rate, and the two effects showed no correlation. OptoTD effects showed specificity for the features of the simultaneously presented visual stimuli. OptoTD-induced changes in gamma synchronization, but not firing rates, were predictive of simultaneous changes in the amount of encoded stimulus information. Our findings suggest that one important role of top-down signals is to modulate synchronization and the information encoded by populations of sensory neurons.
PubMed: 38645050
DOI: 10.1101/2024.04.11.589006