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Alzheimer's Research & Therapy May 2024Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and...
BACKGROUND
Autopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies reported that left frontoparietal network functional connectivity (LFPN-FC) confers resilience against beta-amyloid (Aβ)-related cognitive decline in preclinical sporadic and autosomal dominant Alzheimer's disease (AD), as well as against LC-related cognitive changes. Given that the LFPN and the LC play important roles in attention, and attention deficits have been observed early in the disease process, we examined whether LFPN-FC and LC structural health attenuate attentional decline in the context of AD pathology.
METHODS
142 participants from the Harvard Aging Brain Study who underwent resting-state functional MRI, LC structural imaging, PiB(Aβ)-PET, and up to 5 years of cognitive follow-ups were included (mean age = 74.5 ± 9.9 years, 89 women). Cross-sectional robust linear regression associated LC integrity (measured as the average of five continuous voxels with the highest intensities in the structural LC images) or LFPN-FC with Digit Symbol Substitution Test (DSST) performance at baseline. Longitudinal robust mixed effect analyses examined associations between DSST decline and (i) two-way interactions of baseline LC integrity (or LFPN-FC) and PiB or (ii) the three-way interaction of baseline LC integrity, LFPN-FC, and PiB. Baseline age, sex, and years of education were included as covariates.
RESULTS
At baseline, lower LFPN-FC, but not LC integrity, was related to worse DSST performance. Longitudinally, lower baseline LC integrity was associated with a faster DSST decline, especially at PiB > 10.38 CL. Lower baseline LFPN-FC was associated with a steeper decline on the DSST but independent of PiB. At elevated PiB levels (> 46 CL), higher baseline LFPN-FC was associated with an attenuated decline on the DSST, despite the presence of lower LC integrity.
CONCLUSIONS
Our findings demonstrate that the LC can provide resilience against Aβ-related attention decline. However, when Aβ accumulates and the LC's resources may be depleted, the functioning of cortical target regions of the LC, such as the LFPN-FC, can provide additional resilience to sustain attentional performance in preclinical AD. These results provide critical insights into the neural correlates contributing to individual variability at risk versus resilience against Aβ-related cognitive decline.
Topics: Humans; Female; Male; Alzheimer Disease; Aged; Locus Coeruleus; Magnetic Resonance Imaging; Parietal Lobe; Aged, 80 and over; Attention; Frontal Lobe; Positron-Emission Tomography; Cross-Sectional Studies; Neural Pathways; Cognitive Dysfunction; Neuropsychological Tests
PubMed: 38822365
DOI: 10.1186/s13195-024-01485-w -
Brain Stimulation May 2024Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological...
BACKGROUND
Transcranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum.
OBJECTIVE/HYPOTHESIS
Our study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations.
METHODS
We recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS.
RESULTS
Stimulation to DLPFC drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices and high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation.
CONCLUSIONS
By combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.
PubMed: 38821396
DOI: 10.1016/j.brs.2024.05.014 -
NeuroImage May 2024The complexity of fMRI signals quantifies temporal dynamics of spontaneous neural activity, which has been increasingly recognized as providing important insights into...
The complexity of fMRI signals quantifies temporal dynamics of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize multi-scale sample entropy to extract resting-state fMRI complexity in a large healthy adult sample from the Human Connectome Project. We show that fMRI complexity at multiple time scales is heritable in broad brain regions. Heritability estimates are modest and regionally variable. We relate fMRI complexity to brain structure including surface area, cortical myelination, cortical thickness, subcortical volumes, and total brain volume. We find that surface area is negatively correlated with fine-scale complexity and positively correlated with coarse-scale complexity in most cortical regions, especially the association cortex. Most of these correlations are related to common genetic and environmental effects. We also find positive correlations between cortical myelination and fMRI complexity at fine scales and negative correlations at coarse scales in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex, with these correlations mainly attributed to common environmental effects. We detect few significant associations between fMRI complexity and cortical thickness. Despite the non-significant association with total brain volume, fMRI complexity exhibits significant correlations with subcortical volumes in the hippocampus, cerebellum, putamen, and pallidum at certain scales. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI complexity across multiple scales, supporting its potential application as an endophenotype for psychiatric disorders.
PubMed: 38810892
DOI: 10.1016/j.neuroimage.2024.120657 -
Sensors (Basel, Switzerland) May 2024Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time...
PURPOSE
Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation.
METHODS
Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability.
RESULTS
Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment.
CONCLUSIONS
The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.
Topics: Animals; Swine; Female; Disease Models, Animal; Ischemic Stroke; Endothelin-1; Electric Stimulation; Somatosensory Cortex; Brain Ischemia; Monitoring, Physiologic
PubMed: 38793822
DOI: 10.3390/s24102967 -
International Journal of Molecular... May 2024Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to...
Maternal immune activation (MIA) is a risk factor for multiple neurodevelopmental disorders; however, animal models developed to explore MIA mechanisms are sensitive to experimental factors, which has led to complexity in previous reports of the MIA phenotype. We sought to characterize an MIA protocol throughout development to understand how prenatal immune insult alters the trajectory of important neurodevelopmental processes, including the microglial regulation of synaptic spines and complement signaling. We used polyinosinic:polycytidylic acid (polyI:C) to induce MIA on gestational day 9.5 in CD-1 mice, and measured their synaptic spine density, microglial synaptic pruning, and complement protein expression. We found reduced dendritic spine density in the somatosensory cortex starting at 3-weeks-of-age with requisite increases in microglial synaptic pruning and phagocytosis, suggesting spine density loss was caused by increased microglial synaptic pruning. Additionally, we showed dysregulation in complement protein expression persisting into adulthood. Our findings highlight disruptions in the prenatal environment leading to alterations in multiple dynamic processes through to postnatal development. This could potentially suggest developmental time points during which synaptic processes could be measured as risk factors or targeted with therapeutics for neurodevelopmental disorders.
Topics: Animals; Microglia; Mice; Female; Pregnancy; Dendritic Spines; Poly I-C; Complement System Proteins; Prenatal Exposure Delayed Effects; Phagocytosis; Disease Models, Animal; Somatosensory Cortex; Synapses; Neuronal Plasticity
PubMed: 38791517
DOI: 10.3390/ijms25105480 -
Journal of Intelligence May 2024In all vertebrates, visual signals from each visual field project to the opposite midbrain tectum (called the superior colliculus in mammals). The tectum/colliculus...
In all vertebrates, visual signals from each visual field project to the opposite midbrain tectum (called the superior colliculus in mammals). The tectum/colliculus computes visual salience to select targets for context-contingent visually guided behavior: a frog will orient toward a small, moving stimulus (insect prey) but away from a large, looming stimulus (a predator). In mammals, visual signals competing for behavioral salience are also transmitted to the visual cortex, where they are integrated with collicular signals and then projected via the dorsal visual stream to the parietal and frontal cortices. To control visually guided behavior, visual signals must be encoded in body-centered (egocentric) coordinates, and so visual signals must be integrated with information encoding eye position in the orbit-where the individual is looking. Eye position information is derived from copies of eye movement signals transmitted from the colliculus to the frontal and parietal cortices. In the intraparietal cortex of the dorsal stream, eye movement signals from the colliculus are used to predict the sensory consequences of action. These eye position signals are integrated with retinotopic visual signals to generate scaffolding for a visual scene that contains goal-relevant objects that are seen to have spatial relationships with each other and with the observer. Patients with degeneration of the superior colliculus, although they can see, behave as though they are blind. Bilateral damage to the intraparietal cortex of the dorsal stream causes the visual scene to disappear, leaving awareness of only one object that is lost in space. This tutorial considers what we have learned from patients with damage to the colliculus, or to the intraparietal cortex, about how the phylogenetically older midbrain and the newer mammalian dorsal cortical visual stream jointly coordinate the experience of a spatially and temporally coherent visual scene.
PubMed: 38786652
DOI: 10.3390/jintelligence12050050 -
Biomolecules May 2024During the first and second stages of postnatal development, neocortical neurons exhibit a wide range of spontaneous synchronous activity (SSA). Towards the end of the...
During the first and second stages of postnatal development, neocortical neurons exhibit a wide range of spontaneous synchronous activity (SSA). Towards the end of the second postnatal week, the SSA is replaced by a more sparse and desynchronized firing pattern. The developmental desynchronization of neocortical spontaneous neuronal activity is thought to be intrinsically generated, since sensory deprivation from the periphery does not affect the time course of this transition. The extracellular protein reelin controls various aspects of neuronal development through multimodular signaling. However, so far it is unclear whether reelin contributes to the developmental desynchronization transition of neocortical neurons. The present study aims to investigate the role of reelin in postnatal cortical developmental desynchronization using a conditional reelin knockout (Reln) mouse model. Conditional reelin deficiency was induced during early postnatal development, and Ca recordings were conducted from organotypic cultures (OTCs) of the somatosensory cortex. Our results show that both wild type (wt) and Reln exhibited an SSA pattern during the early postnatal week. However, at the end of the second postnatal week, wt OTCs underwent a transition to a desynchronized network activity pattern, while Reln activity remained synchronous. This changing activity pattern suggests that reelin is involved in regulating the developmental desynchronization of cortical neuronal network activity. Moreover, the developmental desynchronization impairment observed in Reln was rescued when Reln OTCs were co-cultured with wt OTCs. Finally, we show that the developmental transition to a desynchronized state at the end of the second postnatal week is not dependent on glutamatergic signaling. Instead, the transition is dependent on GABAR and GABAR signaling. The results suggest that reelin controls developmental desynchronization through GABAR and GABAR signaling.
Topics: Reelin Protein; Animals; Mice; Neocortex; Mice, Knockout; Nerve Tissue Proteins; Serine Endopeptidases; Extracellular Matrix Proteins; Cell Adhesion Molecules, Neuronal; Neurons; Nerve Net; Somatosensory Cortex
PubMed: 38786001
DOI: 10.3390/biom14050593 -
The Lancet Regional Health. Western... Jun 2024A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However,...
BACKGROUND
A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI).
METHODS
Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated.
FINDINGS
Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found.
INTERPRETATION
This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection.
FUNDING
The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.
PubMed: 38774424
DOI: 10.1016/j.lanwpc.2024.101086 -
Nature Communications May 2024Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether...
Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior.
Topics: Humans; Decision Making; Male; Female; Adult; Brain; Parietal Lobe; Choice Behavior; Young Adult; Uncertainty
PubMed: 38773117
DOI: 10.1038/s41467-024-48342-w -
Journal of Surgical Case Reports May 2024Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system...
Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system melanocytoma are distinct from similarly presenting intracranial neoplasms and can aid in diagnosis prior to histopathological examination. In rare cases, there may be more than one lesion present. We report a case of a 19-year-old woman presenting with progressively worsening headaches, nausea, emesis, and generalized weakness of 2 months. Imaging revealed tumors in the parietal and ipsilateral medial temporal lobe. The patient underwent gross total resection of the parietal lesion which histopathological assessment revealed to be primary intracranial meningeal melanocytoma. This case highlights the utility of specific imaging criteria such as diffusely increased T1 signal without enhancement in the initial diagnostic evaluation of intracranial melanocytoma. We also describe the clinical characteristics, management strategy, and histopathological features of a rare case of a patient with multiple primary intracranial melanocytoma lesions.
PubMed: 38764735
DOI: 10.1093/jscr/rjae332