-
European Journal of Psychotraumatology 2024Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic...
Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging. Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure. Higher PACAP levels were associated with greater EC NDI ( = 0.0099, = 0.032) and lower EC ODI ( = -0.0073, = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures. Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.
Topics: Animals; Humans; Female; Stress Disorders, Post-Traumatic; Pituitary Adenylate Cyclase-Activating Polypeptide; Entorhinal Cortex; Neurites; Amygdala
PubMed: 38590134
DOI: 10.1080/20008066.2024.2335793 -
BioRxiv : the Preprint Server For... Jun 2024Multimodal neuroimaging research plays a pivotal role in understanding the complexities of the human brain and its disorders. Independent component analysis (ICA) has...
Multimodal neuroimaging research plays a pivotal role in understanding the complexities of the human brain and its disorders. Independent component analysis (ICA) has emerged as a widely used and powerful tool for disentangling mixed independent sources, particularly in the analysis of functional magnetic resonance imaging (fMRI) data. This paper extends the use of ICA as a unifying framework for multimodal fusion, introducing a novel approach termed parallel multilink group joint ICA (pmg-jICA). The method allows for the fusion of gray matter maps from structural MRI (sMRI) data to multiple fMRI intrinsic networks, addressing the limitations of previous models. The effectiveness of pmg-jICA is demonstrated through its application to an Alzheimer's dataset, yielding linked structure-function outputs for 53 brain networks. Our approach leverages the complementary information from various imaging modalities, providing a unique perspective on brain alterations in Alzheimer's disease. The pmg-jICA identifies several components with significant differences between HC and AD groups including thalamus, caudate, putamen with in the subcortical (SC) domain, insula, parahippocampal gyrus within the cognitive control (CC) domain, and the lingual gyrus within the visual (VS) domain, providing localized insights into the links between AD and specific brain regions. In addition, because we link across multiple brain networks, we can also compute functional network connectivity (FNC) from spatial maps and subject loadings, providing a detailed exploration of the relationships between different brain regions and allowing us to visualize spatial patterns and loading parameters in sMRI along with intrinsic networks and FNC from the fMRI data. In essence, developed approach combines concepts from joint ICA and group ICA to provide a rich set of output characterizing data-driven links between covarying gray matter networks, and a (potentially large number of) resting fMRI networks allowing further study in the context of structure/function links. We demonstrate the utility of the approach by highlighting key structure/function disruptions in Alzheimer's individuals.
PubMed: 38585901
DOI: 10.1101/2024.03.21.586091 -
CNS Neuroscience & Therapeutics Apr 2024This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's...
OBJECTIVE
This study aimed to investigate whether spontaneous brain activity can be used as a prospective indicator to identify cognitive impairment in patients with Parkinson's disease (PD).
METHODS
Resting-state functional magnetic resonance imaging (RS-fMRI) was performed on PD patients. The cognitive level of patients was assessed by the Montreal Cognitive Assessment (MoCA) scale. The fractional amplitude of low-frequency fluctuation (fALFF) was applied to measure the strength of spontaneous brain activity. Correlation analysis and between-group comparisons of fMRI data were conducted using Rest 1.8. By overlaying cognitively characterized brain regions and defining regions of interest (ROIs) based on their spatial distribution for subsequent cognitive stratification studies.
RESULTS
A total of 58 PD patients were enrolled in this study. They were divided into three groups: normal cognition (NC) group (27 patients, average MoCA was 27.96), mild cognitive impairment (MCI) group (21 patients, average MoCA was 23.52), and severe cognitive impairment (SCI) group (10 patients, average MoCA was 17.3). It is noteworthy to mention that those within the SCI group exhibited the most advanced chronological age, with an average of 74.4 years, whereas the MCI group displayed a higher prevalence of male participants at 85.7%. It was found hippocampal regions were a stable representative brain region of cognition according to the correlation analysis between the fALFF of the whole brain and cognition, and the comparison of fALFF between different cognitive groups. The parahippocampal gyrus was the only region with statistically significant differences in fALFF among the three cognitive groups, and it was also the only brain region to identify MCI from NC, with an AUC of 0.673. The paracentral lobule, postcentral gyrus was the region that identified SCI from NC, with an AUC of 0.941. The midbrain, hippocampus, and parahippocampa gyrus was the region that identified SCI from MCI, with an AUC of 0.926.
CONCLUSION
The parahippocampal gyrus was the potential brain region for recognizing cognitive impairment in PD, specifically for identifying MCI. Thus, the fALFF of parahippocampal gyrus is expected to contribute to future study as a multimodal fingerprint for early warning.
Topics: Humans; Male; Aged; Female; Parkinson Disease; Prospective Studies; Brain; Cognitive Dysfunction; Magnetic Resonance Imaging; Hippocampus
PubMed: 38584347
DOI: 10.1111/cns.14706 -
Neuropsychologia Jun 2024The relation between the processing of space and time in the brain has been an enduring cross-disciplinary question. Grid cells have been recognized as a hallmark of the...
The relation between the processing of space and time in the brain has been an enduring cross-disciplinary question. Grid cells have been recognized as a hallmark of the mammalian navigation system, with recent studies attesting to their involvement in the organization of conceptual knowledge in humans. To determine whether grid-cell-like representations support temporal processing, we asked subjects to mentally simulate changes in age and time-of-day, each constituting "trajectory" in an age-day space, while undergoing fMRI. We found that grid-cell-like representations supported trajecting across this age-day space. Furthermore, brain regions concurrently coding past-to-future orientation positively modulated the magnitude of grid-cell-like representation in the left entorhinal cortex. Finally, our findings suggest that temporal processing may be supported by spatially modulated systems, and that innate regularities of abstract domains may interface and alter grid-cell-like representations, similarly to spatial geometry.
Topics: Humans; Male; Magnetic Resonance Imaging; Female; Adult; Grid Cells; Young Adult; Brain Mapping; Time Perception; Space Perception; Entorhinal Cortex; Imagination; Brain; Image Processing, Computer-Assisted
PubMed: 38574806
DOI: 10.1016/j.neuropsychologia.2024.108878 -
Frontiers in Neuroscience 2024When faced with a conflict or dilemma, we tend to postpone or even avoid making a decision. This phenomenon is known as decisional procrastination. Here, we investigated...
When faced with a conflict or dilemma, we tend to postpone or even avoid making a decision. This phenomenon is known as decisional procrastination. Here, we investigated the neural correlates of this phenomenon, in particular the parahippocampal gyrus (PHG) that has previously been identified in procrastination studies. In this study, we applied an individual difference approach to evaluate participants' spontaneous neural activity in the PHG and their decisional procrastination levels, assessed outside the fMRI scanner. We discovered that the fractional amplitude of low-frequency fluctuations (fALFF) in the caudal PHG (cPHG) could predict participants' level of decisional procrastination, as measured by the avoidant decision-making style. Importantly, participants' self-esteem mediated the relationship between the cPHG and decisional procrastination, suggesting that individuals with higher levels of spontaneous activity in the cPHG are likely to have higher levels of self-esteem and thus be more likely to make decisions on time. In short, our study broadens the PHG's known role in procrastination by demonstrating its link with decisional procrastination and the mediating influence of self-esteem, underscoring the need for further exploration of this mediation mechanism.
PubMed: 38567283
DOI: 10.3389/fnins.2024.1341142 -
Journal of Alzheimer's Disease : JAD 2024Histopathologic studies of Alzheimer's disease (AD) suggest that extracellular amyloid-β (Aβ) plaques promote the spread of neurofibrillary tau tangles. However, these...
BACKGROUND
Histopathologic studies of Alzheimer's disease (AD) suggest that extracellular amyloid-β (Aβ) plaques promote the spread of neurofibrillary tau tangles. However, these two proteinopathies initiate in spatially distinct brain regions, so how they interact during AD progression is unclear.
OBJECTIVE
In this study, we utilized Aβ and tau positron emission tomography (PET) scans from 572 older subjects (476 healthy controls (HC), 14 with mild cognitive impairment (MCI), 82 with mild AD), at varying stages of the disease, to investigate to what degree tau is associated with cortical Aβ deposition.
METHODS
Using multiple linear regression models and a pseudo-longitudinal ordering technique, we investigated remote tau-Aβ associations in four pathologic phases of AD progression based on tau spread: 1) no-tau, 2) pre-acceleration, 3) acceleration, and 4) post-acceleration.
RESULTS
No significant tau-Aβ association was detected in the no-tau phase. In the pre-acceleration phase, the earliest stage of tau deposition, associations emerged between regional tau in medial temporal lobe (MTL) (i.e., entorhinal cortex, parahippocampal gyrus) and cortical Aβ in lateral temporal lobe regions. The strongest tau-Aβ associations were found in the acceleration phase, in which tau in MTL regions was strongly associated with cortical Aβ (i.e., temporal and frontal lobes regions). Strikingly, in the post-acceleration phase, including 96% of symptomatic subjects, tau-Aβ associations were no longer significant.
CONCLUSIONS
The results indicate that associations between tau and Aβ are stage-dependent, which could have important implications for understanding the interplay between these two proteinopathies during the progressive stages of AD.
Topics: Humans; tau Proteins; Amyloid beta-Peptides; Alzheimer Disease; Temporal Lobe; Cognitive Dysfunction; Positron-Emission Tomography; Proteostasis Deficiencies
PubMed: 38552116
DOI: 10.3233/JAD-231362 -
ELife Mar 2024Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. To distinguish these...
Grid firing fields have been proposed as a neural substrate for spatial localisation in general or for path integration in particular. To distinguish these possibilities, we investigate firing of grid and non-grid cells in the mouse medial entorhinal cortex during a location memory task. We find that grid firing can either be anchored to the task environment, or can encode distance travelled independently of the task reference frame. Anchoring varied between and within sessions, while spatial firing of non-grid cells was either coherent with the grid population, or was stably anchored to the task environment. We took advantage of the variability in task-anchoring to evaluate whether and when encoding of location by grid cells might contribute to behaviour. We find that when reward location is indicated by a visual cue, performance is similar regardless of whether grid cells are task-anchored or not, arguing against a role for grid representations when location cues are available. By contrast, in the absence of the visual cue, performance was enhanced when grid cells were anchored to the task environment. Our results suggest that anchoring of grid cells to task reference frames selectively enhances performance when path integration is required.
Topics: Mice; Animals; Entorhinal Cortex; Cues; Action Potentials; Space Perception; Models, Neurological
PubMed: 38546203
DOI: 10.7554/eLife.89356 -
Social Cognitive and Affective... Apr 2024Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region...
Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region involved in perceiving and comprehending the sequential dynamics of social actions, in detecting actions that either conform to or deviate from social norms. Participants engaged in a goal-directed task in which they observed others navigating towards a goal. The trajectories demonstrated either norm-violating (trespassing forbidden zones) or norm-following behaviors (avoiding forbidden zones). Results revealed that observing social norm-violating behaviors engaged the bilateral posterior cerebellar Crus 2 and the right temporoparietal junction (TPJ) from the mentalizing network, and the parahippocampal gyrus (PHG) to a greater extent than observing norm-following behaviors. These mentalizing regions were also activated when comparing social sequences against non-social and non-sequential control conditions. Reproducing norm-violating social trajectories observed earlier, activated the left cerebellar Crus 2 and the right PHG compared to reproducing norm-following trajectories. These findings illuminate the neural mechanisms in the cerebellum associated with detecting norm transgressions during social navigation, emphasizing the role of the posterior cerebellum in detecting and signaling deviations from anticipated sequences.
Topics: Humans; Cerebellum; Male; Female; Young Adult; Adult; Magnetic Resonance Imaging; Brain Mapping; Social Norms; Social Perception; Social Behavior; Mentalization
PubMed: 38536051
DOI: 10.1093/scan/nsae027 -
Brain Stimulation 2024Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is a common form of drug-resistant focal epilepsy in adults. Treatment for pharmacoresistant...
BACKGROUND
Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is a common form of drug-resistant focal epilepsy in adults. Treatment for pharmacoresistant patients remains a challenge, with deep brain stimulation (DBS) showing promise for alleviating intractable seizures. This study explores the efficacy of low frequency stimulation (LFS) on specific neuronal targets within the entorhinal-hippocampal circuit in a mouse model of MTLE.
OBJECTIVE
Our previous research demonstrated that LFS of the medial perforant path (MPP) fibers in the sclerotic hippocampus reduced seizures in epileptic mice. Here, we aimed to identify the critical neuronal population responsible for this antiepileptic effect by optogenetically stimulating presynaptic and postsynaptic compartments of the MPP-dentate granule cell (DGC) synapse at 1 Hz. We hypothesize that specific targets for LFS can differentially influence seizure activity depending on the cellular identity and location within or outside the seizure focus.
METHODS
We utilized the intrahippocampal kainate (ihKA) mouse model of MTLE and targeted specific neural populations using optogenetic stimulation. We recorded intracranial neuronal activity from freely moving chronically epileptic mice with and without optogenetic LFS up to 3 h.
RESULTS
We found that LFS of MPP fibers in the sclerotic hippocampus effectively suppressed epileptiform activity while stimulating principal cells in the MEC had no impact. Targeting DGCs in the sclerotic septal or non-sclerotic temporal hippocampus with LFS did not reduce seizure numbers but shortened the epileptiform bursts.
CONCLUSION
Presynaptic stimulation of the MPP-DGC synapse within the sclerotic hippocampus is critical for seizure suppression via LFS.
Topics: Animals; Hippocampus; Mice; Epilepsy, Temporal Lobe; Entorhinal Cortex; Seizures; Deep Brain Stimulation; Male; Optogenetics; Disease Models, Animal; Perforant Pathway; Mice, Inbred C57BL
PubMed: 38531502
DOI: 10.1016/j.brs.2024.03.017 -
Npj Aging Mar 2024Several studies have found associations between poor oral health, particularly tooth loss and cognitive decline. However, the specific brain regions affected by tooth...
Several studies have found associations between poor oral health, particularly tooth loss and cognitive decline. However, the specific brain regions affected by tooth loss and the probable causes remain unclear. We conducted a population-based longitudinal cohort study in Nakajima, Nanao City, Japan. Between 2016 and 2018, 2454 residents aged ≥60 participated, covering 92.9% of the local age demographics. This study used comprehensive approach by combining detailed dental examinations, dietary assessments, magnetic resonance imaging (MRI) analysis, and cognitive evaluations. Tooth loss, even in cognitively normal individuals, is associated with parahippocampal gyrus atrophy and increased WMH volume, both of which are characteristics of dementia. Tooth loss was associated with altered dietary patterns, notably a reduction in plant-based food intake and an increase in fatty, processed food intake. This study highlights a possible preventative pathway where oral health may play a significant role in preventing the early neuropathological shifts associated with dementia.
PubMed: 38519528
DOI: 10.1038/s41514-024-00146-4