Bilateral Cortex Research Articles

Epigenetic modifications in the motor cortex caused by exercise or pharmacological inhibition of histone deacetylases (HDACs) after intracerebral hemorrhage (ICH)

Epigenetic regulation is expected to provide an enriched platform for neurorehabilitation of post-stroke patients. Acetylation of specific lysine residues in histones is a potent epigenetic target essential for transcriptional regulation. Exercise modulates histone acetylation and gene expression in neuroplasticity in the brain. This study sought to examine the effect of epigenetic treatment using a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaB), and exercise on epigenetic markers in the bilateral motor cortex after intracerebral hemorrhage (ICH) to identify a more enriched neuronal condition for neurorehabilitation. Forty-one male Wistar rats were randomly divided into five groups: sham (n = 8), control (n = 9), NaB, exercise (n = 8), and NaB and exercise (n = 8). Intraperitoneal administration of an HDAC inhibitor (300 mg/kg NaB) and treadmill exercise (11 m/min for 30 min) was conducted five days a week for approximately-four weeks. ICH specifically decreased the acetylation level of histone H4 in the ipsilateral cortex, and HDAC inhibition with NaB increased the acetylation level of histone H4 over the sham level, accompanied by an improvement in motor function as assessed by the cylinder test. Exercise increased the acetylation levels of histones (H3 and H4) in the bilateral cortex. Synergistic effects of exercise and NaB were not observed during histone acetylation. Pharmacological treatment with a HDAC inhibitor and exercise can provide an enriched epigenetic platform for neurorehabilitation in an individual manner.

Differences in Gray Matter Volume in Cerebral Small Vessel Disease Patients with and without Sleep Disturbance.

Recently, there has been increased interest in the relationship between cerebral small vessel disease (CSVD) and circadian rhythm disruption, particularly sleep disturbance. However, the neural mechanism of sleep disturbance in CSVD patients remains poorly understood. The purpose of this study is to explore the gray matter alterations in CSVD patients with and without sleep disturbance. 59 patients with CSVD and 40 healthy controls (HC) were recruited for the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. CSVD patients were categorized into either the good sleepers group (CSVD-GS, n = 23) or the poor sleepers group (CSVD-PS, n = 36) based on PSQI score. Voxel-based morphometry (VBM) analysis was used to assess differences in gray matter volume (GMV) between groups. Multivariate regression analyses were performed to investigate the relationships between sleep quality, GMV, and white matter hyperintensities (WMH). We observed GMV differences between the three groups in the bilateral caudate, right thalamus, bilateral calcarine cortex, left precentral gyrus, right orbitofrontal cortex, left cingulate gyrus, and right sub-gyral temporal lobe. Additionally, the CSVD-PS group exhibited decreased GMV in the bilateral calcarine cortex yet increased GMV in the right caudate compared to the CSVD-GS group. In fully adjusted models, GMV of the right caudate and bilateral calcarine cortex was associated with sleep quality in CSVD patients. The present study revealed structural brain alterations in CSVD patients with sleep disturbance. These findings may provide novel insights into the neural mechanisms of sleep disturbance in CSVD.

Upper limb intelligent feedback robot training significantly activates the cerebral cortex and promotes the functional connectivity of the cerebral cortex in patients with stroke: A functional near-infrared spectroscopy study.

Upper limb intelligence robots are widely used to improve the upper limb function of patients with stroke, but the treatment mechanism is still not clear. In this study, functional near-infrared spectroscopy (fNIRS) was used to evaluate the concentration changes of oxygenated hemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) in different brain regions and functional connectivity (FC) of the cerebral cortex in patients with stroke. Twenty post-stroke patients with upper limb dysfunction were included in the study. They all received three different types of shoulder joint training, namely, active intelligent feedback robot training (ACT), upper limb suspension training (SUS), and passive intelligent feedback robot training (PAS). During the training, activation of the cerebral cortex was detected by fNIRS to obtain the concentration changes of hemoglobin and FC of the cerebral cortex. The fNIRS signals were recorded over eight ROIs: bilateral prefrontal cortices (PFC), bilateral primary motor cortices (M1), bilateral primary somatosensory cortices (S1), and bilateral premotor and supplementary motor cortices (PM). For easy comparison, we defined the right hemisphere as the ipsilesional hemisphere and flipped the lesional right hemisphere in the Nirspark. Compared with the other two groups, stronger cerebral cortex activation was observed during ACT. One-way repeated measures ANOVA revealed significant differences in mean oxy-Hb changes among conditions in the four ROIs: contralesional PFC [F(2, 48) = 6,798, p < 0.01], ipsilesional M1 [F(2, 48) = 6.733, p < 0.01], ipsilesional S1 [F(2, 48) = 4,392, p < 0.05], and ipsilesional PM [F(2, 48) = 3.658, p < 0.05]. Oxy-Hb responses in the contralesional PFC region were stronger during ACT than during SUS (p < 0.01) and PAS (p < 0.05). Cortical activation in the ipsilesional M1 was significantly greater during ACT than during SUS (p < 0.01) and PAS (p < 0.05). Oxy-Hb responses in the ipsilesional S1 (p < 0.05) and ipsilesional PM (p < 0.05) were significantly higher during ACT than during PAS, and there is no significant difference in mean deoxy-Hb changes among conditions. Compared with SUS, the FC increased during ACT, which was characterized by the enhanced function of the ipsilesional cortex (p < 0.05), and there was no significant difference in FC between the ACT and PAS. The study found that cortical activation during ACT was higher in the contralesional PFC, and ipsilesional M1 than during SUS, and showed tighter cortical FC between the cortices. The activation of the cerebral cortex of ACT was significantly higher than that of PAS, but there was no significant difference in FC. Our research helps to understand the difference in cerebral cortex activation between upper limb intelligent feedback robot rehabilitation and other rehabilitation training and provides an objective basis for the further application of upper limb intelligent feedback robots in the field of stroke rehabilitation.

Altered Neural Pathways and Related Brain Remodeling: A Rat Study Using Different Nerve Reconstructions.

Function recovery is related to cortical plasticity. The brain remodeling patterns induced by alterations in peripheral nerve pathways with different nerve reconstructions are unknown. To explore brain remodeling patterns related to alterations in peripheral neural pathways after different nerve reconstruction surgeries. Twenty-four female Sprague-Dawley rats underwent complete left brachial plexus nerve transection, together with the following interventions: no nerve repair (n = 8), grafted nerve repair (n = 8), and phrenic nerve transfer (n = 8). Resting-state functional MR images of brain were acquired at the end of seventh month postsurgery. Amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) were compared among 3 groups. Behavioral observation and electromyography assessed nerve regeneration. Compared with brachial plexus injury group, ALFF and ReHo of left entorhinal cortex decreased in nerve repair and nerve transfer groups. The nerve transfer group showed increased ALFF and ReHo than nerve repair group in left caudate putamen, right accumbens nucleus shell (AcbSh), and right somatosensory cortex. The FC between right somatosensory cortex and bilateral piriform cortices and bilateral somatosensory cortices increased in nerve repair group than brachial plexus injury and nerve transfer groups. The nerve transfer group showed increased FC between right somatosensory cortex and areas including left corpus callosum, left retrosplenial cortex, right parietal association cortex, and right dorsolateral thalamus than nerve repair group. Entorhinal cortex is a key brain area in recovery of limb function after nerve reconstruction. Nerve transfer related brain remodeling mainly involved contralateral sensorimotor areas, facilitating directional "shifting" of motor representation.

Morphological and Structural Network Analysis of Sporadic Alzheimer's Disease Brains Based on the APOE4 Gene.

Alzheimer's disease (AD) is an increasingly common type of dementia. Apolipoprotein E (APOE) gene is a strong risk factor for AD. Here, we explored alterations in grey matter structure (GMV) and networks in AD, as well as the effects of the APOEɛ4 allele on neuroimaging regions based on structural magnetic resonance imaging (sMRI). All subjects underwent an sMRI scan. GMV and cortical thickness were calculated using voxel-based morphological analysis, and structural networks were constructed based on graph theory analysis to compare differences between AD and normal controls. The volumes of grey matter in the bilateral inferior temporal gyrus, right middle temporal gyrus, right inferior parietal lobule, right limbic lobe, right frontal lobe, left anterior cingulate gyrus, and bilateral olfactory cortex of patients with AD were significantly decreased. The cortical thickness in patients with AD was significantly reduced in the left lateral occipital lobe, inferior parietal lobe, orbitofrontal region, precuneus, superior parietal gyrus, right precentral gyrus, middle temporal gyrus, pars opercularis gyrus, insular gyrus, superior marginal gyrus, bilateral fusiform gyrus, and superior frontal gyrus. In terms of local properties, there were significant differences between the AD and control groups in these areas, including the right bank, right temporalis pole, bilateral middle temporal gyrus, right transverse temporal gyrus, left postcentral gyrus, and left parahippocampal gyrus. There were significant differences in the morphological and structural covariate networks between AD patients and healthy controls under APOEɛ4 allele effects.

Cortical projection to the subventricular zone and its effect on adult neurogenesis in mice

Various brain regions/nuclei project axons to the subventricular zone (SVZ), a postnatal neurogenic niche. In adults, neurogenesis is controlled by neuronal activity, via neurotransmitters. Glutamate is a major excitatory neurotransmitter, and glutamate receptors are expressed in SVZ cells. Although the cerebral cortex is a major source of glutamate and the medial cortex projects axons to the medial striatum next to the SVZ, it remains unclear whether cortical neurons regulate adult neurogenesis in vivo. First, to analyze axonal projection, plasmid vector expressing DsRed was introduced to the medial cortex by in utero electroporation. At the adult stage, DsRed-labeled axons were detected in the dorsolateral, striatal, and septal areas of the SVZ, and where they were in contact with neuroblasts. Furthermore, maturation of the cortical projection and the SVZ appeared to synchronize during postnatal stages. Next, stab injuries were made in the bilateral medial cortex to interrupt cortical input to the SVZ. At 17 days post-injury, cell proliferation in the SVZ and tangential migration of neuroblasts to the olfactory bulb were not significantly affected. There were clusters of neuroblasts in the striatum close to the SVZ in all experimental groups, but the number and size of neuroblast clusters were significantly larger in the medial cortex-injured group compared with the other experimental groups. These neuroblast clusters had a morphology of tangentially migrating cells to the olfactory bulb. These results suggest that cortical input to the SVZ inhibits the radial migration of neuroblasts to converge with the migration pathway in vivo.

In vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease

Synapse loss has been considered as a major pathological change in Alzheimer’s disease (AD). It remains unclear about whether and how synapse loss relates to functional and structural connectivity dysfunction in AD. We measured synaptic vesicle glycoprotein 2 A (SV2A) binding using 18F-SynVesT-1 PET to evaluate synaptic alterations in 33 participants with AD, 31 with mild cognitive impairment (MCI), and 30 controls. We examined the correlation between synaptic density and cognitive function. Functional MRI was performed to analyze functional connectivity in lower synaptic density regions. We tracked the white matter tracts between impaired functional connectivity regions using Diffusion MRI. In AD group, lower synaptic density in bilateral cortex and hippocampus was found when compared with controls. The synaptic density changes in right insular cortex and bilateral caudal middle frontal gyrus (MFG) were correlated with cognitive decline. Among them, right MFG synaptic density was positively associated with right MFG - bilateral superior frontal gyrus (SFG) functional connectivity. AD had lower probability of tract (POT) between right MFG and SFG than controls, which was significantly associated with global cognition. These findings provide evidence supporting synapse loss contributes to functional and related structural connectivity alterations underlying cognitive impairment of AD.

Reduced gamma oscillation during visual processing of the mother's face in children with autism spectrum disorder: A pilot study.

This study aimed to investigate gamma oscillations related to face processing of children with autism spectrum disorders and typically developed children using magnetoencephalography. We developed stimuli that included naturalistic real-time eye-gaze situations between participants and their mothers. Eighteen young children with autism spectrum disorders (62-97 months) and 24 typically developed children (61-79 months) were included. The magnetoencephalography data were analyzed in the bilateral banks of the superior temporal sulcus, fusiform gyrus, and pericalcarine cortex for frequency ranges 30-59 and 61-90 Hz. The gamma oscillation normalized values were calculated to compare the face condition (children gazing at mother's face) and control measurements (baseline) using the following formula: (face - control)/(face + control). The results revealed significant differences in gamma oscillation normalized values in the low gamma band (30-59 Hz) in the right banks of the superior temporal sulcus, right fusiform gyrus, and right pericalcarine cortex between children with autism spectrum disorders and typically developed children. Furthermore, there were significant differences in gamma oscillation normalized values in the high gamma band (61-90 Hz) in the right banks of the superior temporal sulcus, bilateral fusiform gyrus, and bilateral pericalcarine cortex between the groups. This report is the first magnetoencephalography study revealing atypical face processing in young children with autism spectrum disorders using relevant stimuli between participants and their mothers. Our naturalistic paradigm provides a useful assessment of social communication traits and a valuable insight into the underlying neural mechanisms in children with autism spectrum disorders.

Visible CCD Camera-Guided Photoacoustic Imaging System for Precise Navigation during Functional Rat Brain Imaging

In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible user interfaces. We introduce a new visible charge-coupled device (CCD) camera-guided photoacoustic imaging (ViCPAI) system that integrates an ultrasound (US) transducer and a data acquisition platform with a CCD camera for positioning. The CCD camera accurately positions the US probe at the measurement location. The programmable MATLAB-based platform has an intuitive user interface. In vitro carbon fiber and in vivo animal experiments were performed to investigate the precise positioning and imaging capabilities of the ViCPAI system. We demonstrated real-time capturing of bilateral cerebral hemodynamic changes during (1) forelimb electrical stimulation under normal conditions, (2) forelimb stimulation after right brain focal photothrombotic ischemia (PTI) stroke, and (3) progression of KCl-induced cortical spreading depression (CSD). The ViCPAI system accurately located target areas and achieved reproducible positioning, which is crucial in animal and clinical experiments. In animal experiments, the ViCPAI system was used to investigate bilateral cerebral cortex responses to left forelimb electrical stimulation before and after stroke, showing that the CBV and SO2 in the right primary somatosensory cortex of the forelimb (S1FL) region were significantly changed by left forelimb electrical stimulation before stroke. No CBV or SO2 changes were observed in the bilateral cortex in the S1FL area in response to left forelimb electrical stimulation after stroke. While monitoring CSD progression, the ViCPAI system accurately locates the S1FL area and returns to the same position after the probe moves, demonstrating reproducible positioning and reducing positioning errors. The ViCPAI system utilizes the real-time precise positioning capability of CCD cameras to overcome various challenges in preclinical and clinical studies.

Functional Connectivity Pattern Using Resting-state fMRI as an Assessment Tool for Spatial Neglect during the Recovery Stage of Stroke: A Pilot Study.

To determine if functional connectivity measured with resting-state functional MRI could be used as a tool to assess unilateral spatial neglect during stroke recovery. Resting-state functional MRI was performed on 13 stroke patients with lesions in the right cerebral hemisphere and 31 healthy subjects. The functional connectivity score was defined as a correlation of a target region with the right inferior parietal lobule. Spatial neglect was measured with a behavioral inattention test. First, the functional connectivity scores between the right inferior parietal lobule and right inferior frontal gyrus, including the opercular and triangular parts, were significantly decreased in stroke patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Second, the functional connectivity scores between the bilateral inferior parietal lobules were also significantly decreased in patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Third, negative functional connectivity scores between the right inferior parietal lobule and bilateral medial orbitofrontal cortexes, which are related to the default mode network, were detected in patients without unilateral spatial neglect in contrast to a reduction of this negative tendency in patients with unilateral spatial neglect. The functional connectivity scores between these regions were significantly different between patients with and without unilateral spatial neglect and were negatively correlated with the behavioral inattention test score. Though still in the pilot research stage and using a small number of cases, our findings are consistent with the hypothesis that functional connectivity maps generated with resting-state functional MRI may be used as a tool to evaluate unilateral spatial neglect during stroke recovery.

Baseline cerebral structural morphology predict freezing of gait in early drug-naïve Parkinson’s disease

Freezing of gait (FOG) greatly impacts the daily life of patients with Parkinson’s disease (PD). However, predictors of FOG in early PD are limited. Moreover, recent neuroimaging evidence of cerebral morphological alterations in PD is heterogeneous. We aimed to develop a model that could predict the occurrence of FOG using machine learning, collaborating with clinical, laboratory, and cerebral structural imaging information of early drug-naïve PD and investigate alterations in cerebral morphology in early PD. Data from 73 healthy controls (HCs) and 158 early drug-naïve PD patients at baseline were obtained from the Parkinson’s Progression Markers Initiative cohort. The CIVET pipeline was used to generate structural morphological features with T1-weighted imaging (T1WI). Five machine learning algorithms were calculated to assess the predictive performance of future FOG in early PD during a 5-year follow-up period. We found that models trained with structural morphological features showed fair to good performance (accuracy range, 0.67–0.73). Performance improved when clinical and laboratory data was added (accuracy range, 0.71–0.78). For machine learning algorithms, elastic net-support vector machine models (accuracy range, 0.69–0.78) performed the best. The main features used to predict FOG based on elastic net-support vector machine models were the structural morphological features that were mainly distributed in the left cerebrum. Moreover, the bilateral olfactory cortex (OLF) showed a significantly higher surface area in PD patients than in HCs. Overall, we found that T1WI morphometric markers helped predict future FOG occurrence in patients with early drug-naïve PD at the individual level. The OLF exhibits predominantly cortical expansion in early PD.

Neural similarities and differences between native and second languages in the bilateral fusiform cortex in Chinese-English bilinguals

In the field of bilingualism, researchers have proposed an assimilation hypothesis that posits that bilinguals apply the neural network of their native language to process their second language. In Chinese-English bilinguals, the bilateral fusiform gyrus has been identified as the key brain region showing the assimilation process. Specifically, in contrast to left-lateralized activation in the fusiform gyrus in native English speakers, Chinese-English bilinguals recruit the bilateral fusiform cortex to process English words as they do in the processing of Chinese characters. Nevertheless, it is unclear which type of information processing is assimilated in the fusiform gyrus. Using representational similarity analysis (RSA) and psychophysiological interaction (PPI) analysis, this study examined the differences in information representation and functional connectivity between both languages in the fusiform subregions in Chinese-English bilinguals. Univariate analysis revealed that both Chinese and English naming elicited strong activations in the bilateral fusiform gyrus, which confirmed the assimilation process at the activation intensity level. RSA indicated that the neural pattern of English phonological information was assimilated by Chinese in the anterior and middle right fusiform gyrus, while those of orthographic and visual form information were not. Further PPI analysis demonstrated that the neural representation of English phonological information in the right anterior fusiform subregion was related to its interaction with the frontotemporal areas for high-level linguistic processing, while the neural representation of English orthographic information in the right middle fusiform subregion was linked to its interaction with the left inferior occipital cortex for visual processing. These results suggest that, despite the recruitment of similar neural resources in one's native and second languages, the assimilation of information representation is limited in the bilateral fusiform cortex. Our results shed light on the neural mechanisms of second language processing.

Time-locked auditory cortical responses in the high-gamma band: A window into primary auditory cortex.

Primary auditory cortex is a critical stage in the human auditory pathway, a gateway between subcortical and higher-level cortical areas. Receiving the output of all subcortical processing, it sends its output on to higher-level cortex. Non-invasive physiological recordings of primary auditory cortex using electroencephalography (EEG) and magnetoencephalography (MEG), however, may not have sufficient specificity to separate responses generated in primary auditory cortex from those generated in underlying subcortical areas or neighboring cortical areas. This limitation is important for investigations of effects of top-down processing (e.g., selective-attention-based) on primary auditory cortex: higher-level areas are known to be strongly influenced by top-down processes, but subcortical areas are often assumed to perform strictly bottom-up processing. Fortunately, recent advances have made it easier to isolate the neural activity of primary auditory cortex from other areas. In this perspective, we focus on time-locked responses to stimulus features in the high gamma band (70-150 Hz) and with early cortical latency (∼40 ms), intermediate between subcortical and higher-level areas. We review recent findings from physiological studies employing either repeated simple sounds or continuous speech, obtaining either a frequency following response (FFR) or temporal response function (TRF). The potential roles of top-down processing are underscored, and comparisons with invasive intracranial EEG (iEEG) and animal model recordings are made. We argue that MEG studies employing continuous speech stimuli may offer particular benefits, in that only a few minutes of speech generates robust high gamma responses from bilateral primary auditory cortex, and without measurable interference from subcortical or higher-level areas.

Assessment of gray matter microstructure and synaptic density in Alzheimer’s Disease: a multimodal imaging study with DWI and SV2A PET

AbstractBackgroundDiffusion weighted imaging (DWI) is proposed to show alterations to microscopic barriers (O'Donnell, et al. 2011) associated with neurodegeneration (Jacobs, et al. 2013). Positron emission tomography (PET) imaging has also been used to measure synaptic density. Previously, we have shown that synaptic density is lower in Alzheimer’s Disease (AD) participants (Mecca, et al. 2020) and is correlated with cognitive performance in patients with AD. Here, we aim to investigate the relationship between DWI metrics and synaptic density in gray matter in the hope of better understanding of AD neurobiology.MethodThirty‐four amyloid positive participants with clinical diagnosis of AD and 18 amyloid negative cognitively normal (CN) participants were included in this study. Early AD‐affected regions (entorhinal cortex, hippocampus, posterior cingulate, and precuneus) were chosen as the primary region of interest (ROI). Synaptic density was measured using [11C]UCB‐J PET where the distribution volume ratio in ROIs was computed using SRTM2 with cerebellum as reference region. Average axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) within each ROIs was computed using Freesurfer 6. Between group comparisons were performed using an unpaired t‐test. Association between gray matter DWI metrics and synaptic density was assessed using univariate regression analyses.ResultsAxD was significantly higher in AD participants in entorhinal cortex and hippocampus bilaterally as well as right posterior cingulate and left precuneus. FA was significantly lower in left hippocampus, and significantly higher in right hippocampus and right posterior cingulate in AD participants. MD was significantly higher in AD participants in bilateral entorhinal cortex, left hippocampus and left precuneus. RD was significantly higher in AD participants in left precuneus, bilateral entorhinal cortex and hippocampus. Within AD participants, synaptic density was inversely correlated with AxD, MD, and RD in the entorhinal cortex and hippocampus bilaterally and positively correlated with FA in the left precuneus. These associations were absent in the CN group.ConclusionWe found that DWI metrics had significant correlation with synaptic density in Early AD‐affected regions in participants with AD, but not in CN participants. We hypothesize that DWI outcome alterations is reflective of gray matter microstructural changes related to synaptic loss.

Assessment of gray matter microstructure and synaptic density in Alzheimer's Disease: a multimodal imaging study with DWI and SV2A PET

AbstractBackgroundDiffusion weighted imaging (DWI) is proposed to show alterations to microscopic barriers (O'Donnell, et al. 2011) associated with neurodegeneration (Jacobs, et al. 2013). Positron emission tomography (PET) imaging has also been used to measure synaptic density. Previously, we have shown that synaptic density is lower in Alzheimer's Disease (AD) participants (Mecca, et al. 2020) and is correlated with cognitive performance in patients with AD. Here, we aim to investigate the relationship between DWI metrics and synaptic density in gray matter in the hope of better understanding of AD neurobiology.MethodThirty‐four amyloid positive participants with clinical diagnosis of AD and 18 amyloid negative cognitively normal (CN) participants were included in this study. Early AD‐affected regions (entorhinal cortex, hippocampus, posterior cingulate, and precuneus) were chosen as the primary region of interest (ROI). Synaptic density was measured using [11C]UCB‐J PET where the distribution volume ratio in ROIs was computed using SRTM2 with cerebellum as reference region. Average axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) within each ROIs was computed using Freesurfer 6. Between group comparisons were performed using an unpaired t‐test. Association between gray matter DWI metrics and synaptic density was assessed using univariate regression analyses.ResultsAxD was significantly higher in AD participants in entorhinal cortex and hippocampus bilaterally as well as right posterior cingulate and left precuneus. FA was significantly lower in left hippocampus, and significantly higher in right hippocampus and right posterior cingulate in AD participants. MD was significantly higher in AD participants in bilateral entorhinal cortex, left hippocampus and left precuneus. RD was significantly higher in AD participants in left precuneus, bilateral entorhinal cortex and hippocampus. Within AD participants, synaptic density was inversely correlated with AxD, MD, and RD in the entorhinal cortex and hippocampus bilaterally and positively correlated with FA in the left precuneus. These associations were absent in the CN group.ConclusionWe found that DWI metrics had significant correlation with synaptic density in Early AD‐affected regions in participants with AD, but not in CN participants. We hypothesize that DWI outcome alterations is reflective of gray matter microstructural changes related to synaptic loss.

Longitudinal medial temporal lobe gray matter volume and cognitive changes in late middle‐aged and older adults with treated and non‐treated obstructive sleep apnea

AbstractBackgroundNeuroimaging studies in obstructive sleep apnea (OSA) have found both gray matter atrophy and hypertrophy in medial temporal lobe subregions, the latter probably reflecting edema. Whether and how these changes progress over time when OSA is treated or untreated remains unclear. Here, we investigated gray matter volume changes in medial temporal lobe subregions in treated OSA, untreated OSA and control participants aged &gt; 55 years. We also explored whether the medial temporal lobe volume at baseline could predict cognitive decline.MethodTwenty‐three non‐treated OSA participants (65.8 ±5.4 years) and twenty controls (64.0 ±6.4 years) were evaluated with overnight polysomnography, MRI session and neuropsychological assessment. Twelve OSA participants then started continuous positive airway pressure (CPAP) therapy and used it at least 4 hours per night, 4 nights per week. Eleven participants refused treatment. Participants were evaluated again with MRI and neuropsychology after 18 months. We extracted the entorhinal, hippocampal and parahippocampal volumes using FreeSurfer 7.1. We performed repeated‐measure ANOVAs with Group (treated OSA, untreated OSA and controls) and Time (baseline and follow‐up) on bilateral volumes. We also performed partial correlations between bilateral medial temporal volumes at baseline and changes in cognition (Montreal Cognitive Assessment, score at follow‐up – baseline) in each group separately. Analyses were corrected for age, sex, and total intracranial volume.ResultWe found a significant Group X Time interaction for bilateral parahippocampal volumes (F = 7.2; p = 0.002) where treated OSA participants showed a decreased volume over time (p tukey&lt;0.001), while no changes occurred in the two other groups. Regarding the predictive value of medial temporal lobe volume, in untreated participants, higher bilateral hippocampal volume at baseline was associated with more severe cognitive decline over time (r = ‐0.77; p = 0.01). In treated participants, higher bilateral entorhinal cortex volume at baseline was associated with more cognitive decline (r = ‐0.74; p = 0.035). No associations were found in controls.ConclusionThese preliminary results showed that presenting hypertrophy of the medial temporal lobe subregions at baseline is associated with worse cognitive outcome at 18‐month follow‐up in OSA participants. In the CPAP group, the decrease in parahippocampal volume might represent a reduction in hypertrophy, possibly by limiting edema.

Altered functional connectivity of the right caudate nucleus in chronic migraine: a resting-state fMRI study

BackgroundThe definitive pathogenic mechanisms underlying chronic migraine (CM) remain unclear. Mounting evidence from functional and structural magnetic resonance imaging (MRI) studies suggests that the caudate nucleus (CN) plays a role in the cognitive, sensory, and emotional integration of pain information in patients with migraine. However, evidence concerning the role played by CN in CM patients is limited. Here, we used the CN as the seed to explore patterns of functional connectivity (FC) among healthy controls (HCs), patients with episodic migraine (EM), and patients with CM.MethodsWe included 25 HCs, 23 EM patients, and 46 CM patients in this study. All participants underwent resting-state functional MRI scans on a GE 3.0T MRI system. We performed seed-based FC analyses among the three groups using the bilateral CNs as seeds. We also compared the subgroups of CM (with and without medication overuse headache, males and females) and performed Pearson’s correlation analyses between FC values and the clinical features of CM patients.ResultsFC values between the right CN and five clusters (mainly involved in emotion, cognition, and sensory-related brain regions) were higher in CM patients than in HCs. Compared to EM patients, enhanced FC values between the bilateral precuneus, left anterior cingulate gyrus, right middle cingulate cortex, right lingual gyrus, and right CN were shown in the CM patients. There were no significant differences between CM patients with and without MOH, males and females. FC values between the bilateral calcarine cortex, lingual gyrus, and right CN were positively correlated with body mass index. Moreover, right CN-related FC values in the left calcarine cortex and right lingual gyrus were inversely correlated with visual analogue scale scores for headaches.ConclusionOur results revealed abnormal right CN-based FC values in CM patients, suggesting dysfunction of brain networks associated with pain perception and multi-regulation (emotion, cognition, and sensory). Aberrant FC of the CN can provide potential neuroimaging markers for the diagnosis and treatment of CM.

Factors associated with the Big 5 personality traits in Alzheimer’s disease and related dementias (ADRD)

AbstractBackgroundInformant ratings of behavior and personality change are the gold standard of measurement in Alzheimer’s disease and related dementias (ADRD) where insight is often impaired, but informant report can be biased by psychosocial factors such as caregiver burden. This study assessed the impact of caregiver burden on informant ratings of patient Big 5 personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, Openness) and associations between degree of discrepancy between informant and patient ratings with cortical volume in regions implicated in loss of insight.MethodA sample of 70 ADRD participants with heterogeneous neurodegenerative clinical phenotypes (Figure 1) and their informants completed the NEO Personality Inventory (NEO‐PI). Disease severity was measured using the Clinical Dementia Rating Scale (CDR). Caregiver burden was measured using the Zarit Burden Interview (ZBI). Discrepancy scores were computed for all NEO‐PI Big 5 scores and a global discrepancy score. Participants were classified as having high/low discrepancy using a median split for each NEO‐PI discrepancy score. T1‐weighted 3T MRI grey matter volumes were normalized to intracranial volume for all ROIs in the Schaefer100×17 parcellation, and linear regression analyses related global difference score to Bonferroni‐corrected atrophy regions.ResultHigher levels of caregiver burden were associated with higher informant ratings of patient Neuroticism (ß = 0.02, p = .013) and lower informant ratings of patient Agreeableness (ß = ‐0.02, p = .0004), Conscientiousness (ß = ‐0.02, p = .005), and Openness (ß = ‐0.01, p = .014) independent of disease severity. Patients with high global discrepancy scores showed reduced cortical volumes in left ventral PFC, right medial PFC, and right superior temporal gyrus. Patients with low discrepancy scores showed relatively preserved cortical volumes in bilateral somatomotor cortex, right posterior cingulate, and left supplementary motor, superior parietal lobule, and postcentral gyrus (all p‐values&lt;.05, Figure 2). Reduced volumes in the high discrepancy group were driven by patients with bvFTD (Figure 3).ConclusionInformant ratings of Big 5 personality factors may be confounded by caregiver burden, highlighting the need for more objective measures of personality and behavior in ADRD. Additionally, high levels of discrepancy between informant and patient ratings of personality may reflect loss of insight secondary to cortical atrophy in frontal and temporal structures.

Reduced expression of perineuronal nets in the normotopic somatosensory cortex of the tish rat

The tish (telencephalic internal structural heterotopia) rat is a naturally occurring and unique model of a malformation of cortical development (MCD) arising from a sponeantous mutation in the Eml1 gene. Tish rats are characterized by a macroscopic bilateral heterotopic dysplastic cortex (HDCx) and an overlaying, intact normotopic neocortex (NNCx). These two cortices are functional and have been reported to innervate and establish connections with subcortical regions including the thalamus, resulting in a dual-cortical representation. Additionally, impaired GABAergic neurotransmission and early-onset spike wave discharge bursts have been reported in developing tish rats. Perineuronal nets (PNNs) are specialized extraceullar matrix structures that predominately surround and stabilize parvalbumin-positive (PV+) GABAergic interneurons and are essential components of the neural landscape. Here, we report a significant reduction in the average number of WFA+-PNNs in the normotopic somatosensory cortex (NSSCx) of the tish rat at two developmental time points, P16 and P35, corresponding to a decrease in the number of PV+ interneurons ensheathed by a PNN in the NSSCx. Compared with control animals, PNN expression was partially, but significantly restored following treatment with insulin-like growth factor 1 (IGF-1). These data suggest that the ‘dual cortical representation’ in the setting of an MCD reduces the cortical activation necessary for proper PNN expression likely contributing to the impairments in GABAergic neurotransmission and network excitability previously identified in the tish rat.

Neural bases of motivated forgetting of autobiographical memories

ABSTRACT It is important for mental health to be able to control unwanted intrusive memories. Previous studies suggest that middle frontal gyrus (MFG) down regulates pathways underlie the suppression of retrieval of general memories. However, the neural basis of motivated forgetting of autobiographical memories is unclear. Therefore, this study used two samples to explore the neural mechanisms of motivated forgetting of self-referential memories. Every participant provided 40 life events (20 negative and 20 neutral) from their past personal experience, and then completed the Think/No-Think task while undergoing functional magnetic resonance imaging (fMRI). The first sample showed a significant reduction in recall in the No-Think condition relative to the Think condition. Attempting to exclude negative autobiographical memories from awareness was associated with increased activity in the right MFG, superior frontal gyrus (SFG), and inferior frontal gyrus (IFG), while reduced activity was observed in the bilateral Brodmann areas BA18 and BA19, bilateral medial prefrontal cortex (mPFC), bilateral precuneus, bilateral post cingulate cortex (PCC), the left parahippocampus, and the left hippocampus. Functional connectivity analyses showed that the right MFG projected into the bilateral mPFC, bilateral precuneus, and bilateral middle occipital gyrus (MOG) for negative autobiographical memories. The second sample replicated the results of the first sample at both the behavioral and brain levels. These results suggest that retrieval suppression of autobiographical memories involve the pathway between the MFG and the mPFC and precuneus to exclude self-referential memories. These results reveal how people engage in motivated forgetting of negative events in their daily lives.