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Scientific Reports Jun 2024Numerous prospective biomarkers are being studied for their ability to diagnose various stages of Alzheimer's disease (AD). High-density electroencephalogram (EEG)...
Numerous prospective biomarkers are being studied for their ability to diagnose various stages of Alzheimer's disease (AD). High-density electroencephalogram (EEG) methods show promise as an accurate, economical, non-invasive approach to measuring the electrical potentials of brains associated with AD. Event-related potentials (ERPs) may serve as clinically useful biomarkers of AD. Through analysis of secondary data, the present study examined the performance and distribution of N4/P6 ERPs across the frontoparietal network (FPN) using EEG topographic mapping. ERP measures and memory as a function of reaction time (RT) were compared between a group of (n = 63) mild untreated AD patients and a control group of (n = 73) healthy age-matched adults. Based on the literature presented, it was expected that healthy controls would outperform patients in peak amplitude and mean component latency across three parameters of memory when measured at optimal N4 (frontal) and P6 (parietal) locations. It was also predicted that the control group would exhibit neural cohesion through FPN integration during cross-modal tasks, thus demonstrating healthy cognitive functioning consistent with older healthy adults. By targeting select frontal and parietal EEG reference channels based on N4/P6 component time windows and positivity, our findings demonstrated statistically significant group variations between controls and patients in N4/P6 peak amplitudes and latencies during cross-modal testing. Our results also support that the N4 ERP might be stronger than its P6 counterpart as a possible candidate biomarker. We conclude through topographic mapping that FPN integration occurs in healthy controls but is absent in AD patients during cross-modal memory tasks.
Topics: Humans; Alzheimer Disease; Male; Female; Electroencephalography; Aged; Parietal Lobe; Evoked Potentials; Frontal Lobe; Biomarkers; Middle Aged; Reaction Time; Case-Control Studies; Brain Mapping; Aged, 80 and over; Memory
PubMed: 38898075
DOI: 10.1038/s41598-024-64699-w -
Nature Communications Jun 2024Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent...
Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.
Topics: Animals; Motor Cortex; Prefrontal Cortex; Movement; Mice; Neurons; Male; Mice, Inbred C57BL; Models, Neurological
PubMed: 38898065
DOI: 10.1038/s41467-024-49615-0 -
Communications Biology Jun 2024The inequitable distribution of economic resources and exposure to adversity between racial groups contributes to mental health disparities within the United States....
The inequitable distribution of economic resources and exposure to adversity between racial groups contributes to mental health disparities within the United States. Consideration of the potential neurodevelopmental consequences, however, has been limited particularly for neurocircuitry known to regulate the emotional response to threat. Characterizing the consequences of inequity on threat neurocircuitry is critical for robust and generalizable neurobiological models of psychiatric illness. Here we use data from the Adolescent Brain and Cognitive Development Study 4.0 release to investigate the contributions of individual and neighborhood-level economic resources and exposure to discrimination. We investigate the potential appearance of race-related differences using both standard methods and through population-level normative modeling. We show that, in a sample of white and Black adolescents, racial inequities in socioeconomic factors largely contribute to the appearance of race-related differences in cortical thickness of threat neurocircuitry. The race-related differences are preserved through the use of population-level models and such models also preserve associations between cortical thickness and specific socioeconomic factors. The present findings highlight that such socioeconomic inequities largely underlie race-related differences in brain morphology. The present findings provide important new insight for the generation of generalizable neurobiological models of psychiatric illness.
Topics: Humans; Adolescent; Male; Female; Socioeconomic Factors; United States; White People; Black or African American; Cerebral Cortex
PubMed: 38898062
DOI: 10.1038/s42003-024-06436-7 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural...
Recent work suggests that the adult human brain is very adaptable when it comes to sensory processing. In this context, it has also been suggested that structural "blueprints" may fundamentally constrain neuroplastic change, e.g. in response to sensory deprivation. Here, we trained 12 blind participants and 14 sighted participants in echolocation over a 10-week period, and used MRI in a pre-post design to measure functional and structural brain changes. We found that blind participants and sighted participants together showed a training-induced increase in activation in left and right V1 in response to echoes, a finding difficult to reconcile with the view that sensory cortex is strictly organized by modality. Further, blind participants and sighted participants showed a training induced increase in activation in right A1 in response to sounds per se (i.e. not echo-specific), and this was accompanied by an increase in gray matter density in right A1 in blind participants and in adjacent acoustic areas in sighted participants. The similarity in functional results between sighted participants and blind participants is consistent with the idea that reorganization may be governed by similar principles in the two groups, yet our structural analyses also showed differences between the groups suggesting that a more nuanced view may be required.
Topics: Humans; Blindness; Male; Adult; Female; Magnetic Resonance Imaging; Auditory Cortex; Visual Cortex; Young Adult; Neuronal Plasticity; Acoustic Stimulation; Brain Mapping; Middle Aged; Auditory Perception; Echolocation
PubMed: 38897817
DOI: 10.1093/cercor/bhae239 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024The left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialization in function, with the left ATL...
The left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialization in function, with the left ATL contributing preferentially to verbal semantic processing. We investigated the cognitive correlates of this organization, using resting-state functional connectivity as a measure of functional segregation between ATLs. We analyzed two independent resting-state fMRI datasets (n = 86 and n = 642) in which participants' verbal semantic expertise was measured using vocabulary tests. In both datasets, people with more advanced verbal semantic knowledge showed weaker functional connectivity between left and right ventral ATLs. This effect was highly specific. It was not observed for within-hemisphere connections between semantic regions (ventral ATL and inferior frontal gyrus (IFG), though it was found for left-right IFG connectivity in one dataset). Effects were not found for tasks probing semantic control, nonsemantic cognition, or face recognition. Our results suggest that hemispheric specialization in the ATLs is not an innate property but rather emerges as people develop highly detailed verbal semantic representations. We speculate that this effect is a consequence of the left ATL's greater connectivity with left-lateralized written word recognition regions, which causes it to preferentially represent meaning for advanced vocabulary acquired primarily through reading.
Topics: Humans; Temporal Lobe; Male; Female; Magnetic Resonance Imaging; Adult; Semantics; Functional Laterality; Young Adult; Brain Mapping; Neural Pathways
PubMed: 38897815
DOI: 10.1093/cercor/bhae256 -
Neurology(R) Neuroimmunology &... Jul 2024A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical,...
BACKGROUND AND OBJECTIVES
A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach.
METHODS
For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures.
RESULTS
We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]- ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR- ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR- ≤ 0.016) and thalamic (FDR- ≤ 0.048) layers, and in the outer caudate layer (FDR- = 0.024). They showed lower R2* values in the outer cortical layer (FDR- = 0.003) and in the outer thalamic layer (FDR- = 0.046) and higher R2* values in all 3 caudate layers (FDR- ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR- ≤ 0.002) and thalamic (FDR- ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR- = 0.005), thalamic R2* (FDR- = 0.004), and caudate MTR (FDR- ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (β ≥ 0.08, all FDR- ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (β = -0.26, FDR- = 0.040). No correlations with choroid plexus volume were found.
DISCUSSION
CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.
Topics: Humans; Middle Aged; Male; Female; Adult; Cross-Sectional Studies; Gray Matter; Cerebral Cortex; Thalamus; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Magnetic Resonance Imaging; Multiparametric Magnetic Resonance Imaging; Multiple Sclerosis; Caudate Nucleus
PubMed: 38896808
DOI: 10.1212/NXI.0000000000200271 -
Acta Neuropathologica Jun 2024TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in...
TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%). Regional TDP-43 pathologic assessment was available for 77% of participants, with hippocampus the most common region. Availability for the TDP-43-related measures increased over time, and was higher in centers with high proportions of participants with clinical FTLD. Part II: In 2142 participants with all TDP-43-related assessments available, 27% of participants had LATE-NC, whereas ALS-TDP or FTLD-TDP (ALS/FTLD-TDP) was present in 9% of participants, and 2% of participants had TDP-43 related to other pathologies ("Other TDP-43"). HS-A was present in 14% of participants, of whom 55% had LATE-NC, 20% ASL/FTLD-TDP, 3% Other TDP-43, and 23% no TDP-43. LATE-NC, ALS/FTLD-TDP, and Other TDP-43, were each associated with higher odds of dementia, HS-A, and hippocampal atrophy, compared to those without TDP-43 pathology. LATE-NC was associated with higher odds for Alzheimer's disease (AD) clinical diagnosis, AD neuropathologic change (ADNC), Lewy bodies, arteriolosclerosis, and cortical atrophy. ALS/FTLD-TDP was associated with higher odds of clinical diagnoses of primary progressive aphasia and behavioral-variant frontotemporal dementia, and cortical/frontotemporal lobar atrophy. When using NACC data for TDP-43-related analyses, researchers should carefully consider the incomplete availability of the different regional TDP-43 assessments, the high frequency of participants with ALS/FTLD-TDP, and the presence of other forms of TDP-43 pathology.
Topics: Humans; Female; Aged; Male; Alzheimer Disease; DNA-Binding Proteins; TDP-43 Proteinopathies; Aged, 80 and over; Databases, Factual; Frontotemporal Lobar Degeneration; Brain; Amyotrophic Lateral Sclerosis; Hippocampus; Middle Aged
PubMed: 38896163
DOI: 10.1007/s00401-024-02728-8 -
Iranian Journal of Public Health Feb 2024Holoprosencephaly, a complicated brain abnormality arising from incomplete prosencephalon cleavage, affects both the forebrain and the face. Holoprosencephaly Type 11,...
Holoprosencephaly, a complicated brain abnormality arising from incomplete prosencephalon cleavage, affects both the forebrain and the face. Holoprosencephaly Type 11, with variable expression or partial penetrance, is caused by pathogenic variants associated with the disrupted Sonic Hedgehog ()-pathway. Herein, we aimed to describe a family with genetic nose problems. After counselling and drawing pedigree in Farhud's Genetic Clinic, Tehran, Iran in 2021, DNA extraction of a proband and a few members of his family (patient and control) was conducted. Whole exome sequencing was utilized for detecting the gene and its variant in the proband with a nose deformity. The results were confirmed with Sanger sequencing. This variant was checked in other members by Sanger sequencing. Analysis of the Exome data showed a heterozygous splicing variant in the gene (NM_016952; c.3276+1G>T) in the proband who had a nose deformity and then the results were confirmed with Sanger sequencing. Such a variant was observed in Proband's brother with a nose deformity and was not observed in Proband's cousin with no abnormal phenotype. Recent investigations, in an Iranian family, with a heterozygous splicing mutation as a human candidate gene are discussed for the first time in relation to the likely pathogenesis of facial deformities, particularly nose deformity, in Holoprosencephaly.
PubMed: 38894838
DOI: 10.18502/ijph.v53i2.14933 -
Frontiers in Endocrinology 2024Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in...
Differential involvement of cAMP/PKA-, PLC/PKC- and Ca/calmodulin-dependent pathways in GnRH-induced prolactin secretion and gene expression in grass carp pituitary cells.
Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg, Pro, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca by Ca influx via L-type voltage-sensitive Ca channel (VSCC) with subsequent CaM expression and NFAT dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca/CaM/CaMK-II pathways but not the signalling events via IP and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca/CaM/CaN/NFAT signalling but not PLC/IP/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca influx via VSCC with parallel rises in PRL release and gene expression in a Ca/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT signalling.
Topics: Animals; Carps; Gonadotropin-Releasing Hormone; Prolactin; Pituitary Gland; Protein Kinase C; Cyclic AMP-Dependent Protein Kinases; Calcium; Type C Phospholipases; Cyclic AMP; Signal Transduction; Calmodulin; Cells, Cultured; Gene Expression
PubMed: 38894746
DOI: 10.3389/fendo.2024.1399274 -
Brain and Behavior Jun 2024Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc)....
INTRODUCTION
Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks.
METHODS
MDD participants (n = 58, mean age = 40.7 years, female = 28) received four ketamine infusions (0.5 mg/kg) 2-3 times weekly. Resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments were collected at baseline and 24 h post-SKI. Static FC (sFC) and dynamic FC variability (dFCv) were calculated from left and right Hb and NAc seeds to all other brain regions. Changes in FC pre-to-post SKI, and correlations with changes with mood and anhedonia were examined. Comparisons of FC between patients and healthy controls (HC) at baseline (n = 55, mean age = 32.6, female = 31), and between HC assessed twice (n = 16) were conducted as follow-up analyses.
RESULTS
Following SKI, significant increases in left Hb-bilateral visual cortex FC, decreases in left Hb-left inferior parietal cortex FC, and decreases in left NAc-right cerebellum FC occurred. Decreased dFCv between left Hb and right precuneus and visual cortex, and decreased dFCv between right NAc and right visual cortex both significantly correlated with improvements in mood ratings. Decreased FC between left Hb and bilateral visual/parietal cortices as well as increased FC between left NAc and right visual/parietal cortices both significantly correlated with improvements in anhedonia. No differences were observed between HC at baseline or over time.
CONCLUSION
Subanesthetic ketamine modulates functional pathways linking the Hb and NAc with visual, parietal, and cerebellar regions in MDD. Overlapping effects between Hb and NAc functional systems were associated with ketamine's therapeutic response.
Topics: Humans; Ketamine; Male; Depressive Disorder, Major; Nucleus Accumbens; Adult; Female; Habenula; Magnetic Resonance Imaging; Middle Aged; Antidepressive Agents; Anhedonia
PubMed: 38894648
DOI: 10.1002/brb3.3511