Inferior Parietal Lobule Research Articles

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression

Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16–24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression—17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD.Clinical trial 1 registration number: NCT02472470 (June 15, 2015).Clinical trial 2 registration number: NCT03708172 (October 17, 2018).

A focus on the multiple interfaces between action and perception and their neural correlates.

Successful behaviour relies on the appropriate interplay between action and perception. The well-established dorsal and ventral stream theories depicted two distinct functional pathways for the processes of action and perception, respectively. In physiological conditions, the two pathways closely cooperate in order to produce successful adaptive behaviour.As the coupling between perception and action exists, this requires an interface that is responsible for a common reading of the two functions. Several studies have proposed different types of perception and action interfaces, suggesting their role in the creation of the shared interaction channel. In the present review, we describe three possible perception and action interfaces: i) the motor code, including common coding approaches, ii) attention, and iii) object affordance; we highlight their potential neural correlates. From this overview, a recurrent neural substrate that underlies all these interface functions appears to be crucial: the parieto-frontal circuit. This network is involved in the mirror mechanism which underlies the perception and action interfaces identified as common coding and motor code theories. The same network is also involved in the spotlight of attention and in the encoding of potential action towards objects; these are manifested in the perception and action interfaces for common attention and object affordance, respectively. Within this framework, most studies were dedicated to the description of the role of the inferior parietal lobule; growing evidence, however, suggests that the superior parietal lobule also plays a crucial role in the interplay between action and perception. The present review proposes a novel model that is inclusive of the superior parietal regions and their relative contribution to the different action and perception interfaces.

80 Longitudinal Development of Response Inhibition in Adolescence and Young Adulthood and Associations with Gray Matter Architecture

Objective:The present study explored how individual differences and development of gray matter architecture in inferior frontal gyri (IFG), anterior cingulate (ACC), and inferior parietal lobe (IPL) relate to development of response inhibition as measured by both the Stop Signal Task (SST) and the Go/No-Go (GNG) task in a longitudinal sample of healthy adolescents and young adults. Reliability of behavioral and neural measures was also explored.Participants and Methods:A total of 145 individuals contributed data from the second through fifth timepoints of an accelerated longitudinal study focused on adolescent brain and behavioral development at the University of Minnesota. At baseline, participants were 9 to 23 years of age and were typically-developing. Assessment waves were spaced approximately 2 years apart. Behavioral measures of response inhibition collected at each assessment included GNG Commission Errors (CE) and the SST Stop Signal Reaction Time (SSRT). Structural T1 MRI scans were collected on a Siemens 3 T Tim Trio and processed with the longitudinal Freesurfer 6.0 pipeline to yield cortical thickness (CT) and surface area values. Regions of interest based on the Desikan-Killiany-Tourville atlas included IFG regions (pars opercularis (PO) and pars triangularis (PT)), ACC and IPL. The cuneus and global brain measures were evaluated as control regions. Retest stability of all measures was calculated using the psych package in R. Mixed linear effects modeling using the lme4 R package identified whether age-based trajectories for SSRTs and GNG CEs best fit linear, quadratic, or inverse curve. Then, disaggregated between- and within-subjects effects of regional cortical architecture measures were added to longitudinal behavioral models to identify individual differences and developmental effects, respectively.Results:Both response inhibition metrics demonstrated fair reliability and were best fit by an inverse age trajectory. Neural measures demonstrated excellent retest stability (all ICCs > 0.834). Age-based analyses of regional CT identified heterogeneous patterns of development, including linear trajectories for ACC and inverse age trajectories for bilateral PT. Individuals with thinner left PO showed worse performance on both response inhibition tasks. SSRTs were related to individual differences in right PO thickness and surface area. A developmental pattern was observed for right PT cortical thickness, where thinning over time was related to better GNG performance. Lower surface area of the right PT was related to worse GNG performance. No individual differences or developmental patterns were observed for the ACC, IPL, cuneus, or global metrics.Conclusions:This study examined the adolescent development of response inhibition and its association with cortical architecture in the IFG, ACC and IPL. Separate response inhibition tasks demonstrated similar developmental patterns with steepest improvements in early adolescence and relationships with left PO thickness, but each measure had unique relationships with other IFG regions. This study indicates that a region of the IFG, the par opercularis, relates to both individual difference and developmental change in response inhibition. These patterns suggest brain-behavior association that could be further explored in functional imaging studies and that may index, in vulnerable individuals, risk for psychopathology.

29 Smoking as a Risk Factor: Altered Brain Activity in Areas Associated with Preclinical Alzheimer's Disease

Objective:Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.Participants and Methods:Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.Results:fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.Conclusions:Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.

57 Sensitivity of functional Near-Infrared Spectroscopy in Individuals with Posterior Cortical Atrophy

Objective:Functional near infrared spectroscopy (fNIRS) is a form of non-invasive neuroimaging that uses light to measure changes in oxygenated and deoxygenated hemoglobin (Yucel et. al., 2021). Relative to fMRI, fNIRS is significantly cheaper and less susceptible to motion artifacts thereby enabling researchers to acquire data in more ecologically valid environments and has a higher temporal resolution that makes it well-suited for connectivity analyses (Tak and Ye, 2014). fNIRS is, however, uniquely limited by cortical anatomy. With a typical probe array having a penetrance depth of up to 3cm, the benefits of fNIRS may be limited by the neocortical atrophy that is characteristic in those with neurodegeneration. We present preliminary findings comparing fNIRS probe sensitivity in older adults diagnosed with posterior cortical atrophy (PCA) relative to cognitively intact older adults using Monte Carlo (MC) simulations. MC simulations offer probabilistic models that simulate photon movement through tissues of interest. We were particularly interested in fNIRS' sensitivity in the occipitoparietal cortices since these are regions characteristically affected in PCA.Participants and Methods:We acquired high resolution structural (T1) MRI on 3 cognitively intact older adults and 3 individuals who received a clinical diagnosis of PCA according to Crutch et al. (2017) criteria. Individual T1 scans were preprocessed and transformed into a twodimensional (2D) surface using FreeSurfer. This continuous 2D surface was then segmented into its main tissue priors, as well as its pial surfaces. Segmented MRIs were then imported into AtlasViewer software and registered to our full head fNIRS probe array via an affine transformation. We embedded the GPU-accelerated Monte Carlo Extreme 3D light transport simulator software (Fang and Boas, 2009) into AtlasViewer which enabled us to launch 10 million photons from each optode, compared to the 1 million that AtlasViewer is set to by default, thereby providing more accurate results (Aasted et. al., 2015). We then assessed the sensitivity profile (log units), a mathematical estimate of optical density, of the inferior and superior occipital gyri, middle occipital gyrus, the superior and inferior parietal lobules, and left and right precunei.Results:Among the regions interrogated, five channels on our fNIRS probe were markedly different between the controls and those with PCA. Specifically, sensitivity values for channels covering the right inferior (hedges g = 8.04) and left superior occipital gyrus (hedges g = 2.46), the right inferior parietal lobule (hedges g = 8.89), and the right (hedges g = 9.43) and left (hedges g = 14.83) precunei were all markedly lower in those with PCA.Conclusions:We provided preliminary evidence that the sensitivity of fNIRS appears to be markedly reduced in those with PCA. This is especially relevant for researchers using fNIRS in populations with neurodegeneration. Future work will evaluate these findings in a larger sample as well as in other neurologic conditions with the goal of helping researchers appropriately power their studies and interpret their results.

56 Stereological Densities of Neuronal Tau Inclusions in Corticobasal Degeneration are Anatomically Distinct in PPA vs bvFTD

Objective:Primary progressive aphasia (PPA) is a dementia syndrome characterized early in its course by gradual dissolution of language and is associated with asymmetric atrophy in the language-dominant hemisphere (usually left). In contrast, behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by a progressive early decline in personality and comportment and is associated with relatively symmetric or rightward predominant bifrontal atrophy. This study analyzed the regional and hemispheric distributions of neuronal tau inclusions of the corticobasal degeneration variant of FTLD-tau pathology (FTLD-CBD) in individuals with PPA or bvFTD. The goal was to establish clinicopathologic concordance between FTLD-CBD and behavioral/comportmental vs aphasic dementia syndromes.Participants and Methods:Seven participants were clinically diagnosed with PPA and 6 were diagnosed with bvFTD. All had FTLD-CBD as the principal neuropathologic diagnosis at postmortem study. Sections from the following cortical regions were stained immunohistochemically with AT-8 to visualize neuronal tau inclusions: bilateral middle frontal gyrus (MFG), inferior parietal lobule (IPL), superior temporal gyrus (STG); and unilateral occipital cortex (OCC). Bilateral anterior temporal lobes (ATL) were analyzed in PPA cases only. Unbiased stereological analysis was performed to compare regional and hemispheric distributions between and within PPA vs. bvFTD groups.Results:Overall neocortical (MFG+STG+IPL) tau densities were significantly greater in the PPA group compared to the bvFTD group (p<0.05). Within the bvFTD group, the highest densities of tau inclusions were observed in the right MFG (mean=6,871.17; SD=3,220). In the PPA group, highest densities were observed in the left ATL (mean=9,901.81; SD=6,871). There was leftward hemispheric asymmetry of tau inclusions in IPL, STG and ATL which trended towards significance in the latter (p=0.083). Cortical distributions were symmetric or rightward predominant within the bvFTD group. Occipital cortex was devoid of inclusions.Conclusions:Preliminary stereological findings of FTLD-CBD tau inclusions suggest that the distributions of pathologic tau are different across two distinct clinical dementia phenotypes. The presence of left-sided neuronal tau inclusions in PPA is concordant with the aphasic phenotype whereas symmetric and frontal-predominant densities in bvFTD are consistent with comportmental dysfunction.

Brain mechanisms of social signalling in live social interactions with autistic and neurotypical adults.

The simple act of watching another person can change a person's behaviour in subtle but important ways; the individual being watched is now capable of signalling to the watcher, and may use this opportunity to communicate to the watcher. Recent data shows that people will spontaneously imitate more when being watched. Here, we examine the neural and cognitive mechanisms of being watched during spontaneous social imitation in autistic and neurotypical adults using fNIRS brain imaging. Participants (n = 44) took part in a block-moving task where they were instructed only to copy the block sequence which people normally do using a straight low action trajectory. Here, the demonstrator sometimes used an atypical 'high' action trajectory, giving participants the opportunity to spontaneously copy the high trajectory even if this slowed their performance. The confederate who demonstrated each block sequence could watch the participant's actions or close her eyes, giving a factorial design with factors of trajectory (high/low) and watched (watched/unwatched). Throughout the task, brain signals were captured from bilateral temporal/parietal/occipital cortex using fNIRS. We found that all participants performed higher actions when being watched by the confederate than when not being watched, with no differences between autistic and neurotypical participants. The unwatched conditions were associated with higher activity of the right inferior parietal lobule in all participants and also engagement of left STS only in autistic participants. These findings are consistent with the claim that people engage different neural mechanisms when watched and unwatched and that participants with autism may engage additional brain mechanisms to match neurotypical behaviour and compensate for social difficulties. However, further studies will be needed to replicate these results in a larger sample of participants.

76 Baseline Frontoparietal Gray Matter Volume Predicts Executive Function Performance at 24-Months in Early and Late Mild Cognitive Impairment

Objective:To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.Participants and Methods:The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.Results:Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.Conclusions:Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.

97 Distinct Clinical and Neuroanatomic Factors Associated with Function-based versus Patient-Reported Outcome Measures After Stroke

Objective:Patient-reported outcome measures provide valuable insights into health status after neurologic disease, but their relationships with function-based outcome measures remain incompletely understood. Here we evaluate the relationship between these two classes of measure using dimensionality-reduction techniques in patients after acute stroke and examine their associated patterns of neuroanatomical injury.Participants and Methods:Fifty-four adults with upper extremity motor deficits were serially assessed at four time points after stroke with functional outcome measures (Upper Extremity Fugl-Meyer, Barthel Index, modified Rankin Scale, Box and Blocks, 9- Hole Peg, Grip Strength) as well as patient-reported measures (PROMIS-Global Physical, Mental, and Social Health, Patient Health Questionnaire-9) of health status. At each timepoint after stroke, exploratory and confirmatory factor analysis were performed to identify and confirm the underlying factorial structure of the entire battery of outcome measures. Multivariate linear regression analysis was used to determine the amount of variance explained by clinical and demographic characteristics on extracted factors. Voxel-Based Lesion Symptom Mapping was used to examine the relationship between factors and patterns of neuroanatomical injury.Results:In the battery of stroke outcome measures, two factors were identified and retained, accounting for >78% of the overall variance across outcomes at every timepoint. Function-based measures loaded onto Factor 1 separately from patient-reported measures which loaded onto Factor 2. Results were consistent at each serial timepoint after stroke. Pre-stroke disability (p=0.03) and amount of damage to the corticospinal tract (p=0.001), explained significant variance in performance on Factor 1 (function-based outcomes), whereas education (p=0.01) and socioeconomic status (p=0.04) explained significant variance in performance on Factor 2 (PROMs). While function-based measures were related to injury to subcortical brain regions known to be important for motor function, patient-reported measures were related to injury to cortical brain regions including the insula and inferior parietal lobe, known to be important for affective processing and social cognition.Conclusions:Two distinct factors representing function-based and patient-reported measures of health status were extracted from the study battery of stroke outcome measures scored across the first year post-stroke. Each factor was associated with injury to brain regions concordant with the content of the represented assessments. These findings emphasize the distinct behavioral elements and neuroanatomical underpinnings of function-based and patient-reported outcome measures after stroke and have potential implications for precision rehabilitation.

The use of theta burst stimulation in patients with schizophrenia - A systematic review.

Transcranial magnetic stimulation (TMS) can offer therapeutic benefits and provide value in neurophysiological research. One of the newer TMS paradigms is theta burst stimulation (TBS) which can be delivered in two patterns: continuous (cTBS - inducing LTD-like effects) and intermittent (iTBS - inducing LTP-like effects). This review paper aims to explore studies that have utilized TBS protocols over different areas of the cortex to study the neurophysiological functions and treatment of patients with schizophrenia. PubMed was searched using the following keywords "schizophrenia", "schizoaffective", or "psychosis", and "theta burst stimulation". Out of the 90 articles which were found, thirty met review inclusion criteria. The inclusion criteria included studying the reported effect (clinical, physiological, or both) of at least one session of TBS on human subjects, and abstracts (at minimum) must have been in English. The main target areas included prefrontal cortex (12 studies - 10 dorsolateral prefrontal cortex (DLPFC), 2 dorsomedial prefrontal cortex (DMPFC)) vermal cerebellum (5), and temporo-parietal cortex (8). Other target areas included inferior parietal lobe (2), and motor cortex (3). TBS neurophysiological effect was explored in 5 studies using functional magnetic resonance image (fMRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), electromyography (EMG) and positron emission topography (PET) scan. Overall, TBS can offer great therapeutic potential as it is well-tolerated, feasible, and has few, if any, adverse effects. TBS may be targeted to treat specific symptomatology, as an augmenting intervention to pharmacotherapy, or even improving patient's insight into their diagnosis.

79 Continuous Theta Burst Stimulation (cTBS) over the Inferior Parietal Cortex Decreases Default Mode Connectivity and Improves Overnight Sleep in People with Insomnia

Objective:Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).Participants and Methods:Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.Results:Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.Conclusions:Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.

The causal effects between selenium levels and the brain cortical structure: A two-sample Mendelian randomization study.

This study utilizes 11 genetic variants associated with Se level variations, extracted from a large-scale genome-wide association study (GWAS) encompassed circulating Se levels (n=5477) and toenail Se levels (n=4162) in the European population. Outcome data were sourced from the summary statistics of the ENIGMA Consortium, comprising GWAS data from 51,666 individuals. The variables include cortical surface area (SA), thickness (TH) at the global level, and 34 functional cortical regions evaluated by magnetic resonance imaging. The inverse-variance-weighted method was used as the primary estimate. Additionally, sensitivity analyses were conducted to detect potential violations of assumptions underlying MR. At the global level, Se levels were not correlated with SA but showed a significant negative correlation with TH (β=-0.00485mm, SE=0.00192, p=.0115). Heterogeneity was observed across different brain regions, with positive correlations found between Se levels and the TH of the parahippocampal gyrus, superior frontal gyrus, and frontal pole, whereas negative correlations were found with the TH of the inferior parietal lobe and middle temporal lobe. Regarding SA, Se levels exhibit positive correlations with the pars triangularis, caudal anterior cingulate, inferior parietal lobe, and banks of the superior temporal sulcus. Conversely, negative correlations were observed with the medial orbitofrontal cortex, posterior cingulate gyrus, insula, and the middle, superior, and transverse gyrus of the temporal lobe. No pleiotropy was detected. This MR study indicated that Se levels causally influence the brain cortical structure.

Altered brain functional networks in schizophrenia with persistent negative symptoms: an activation likelihood estimation meta-analysis

ObjectiveTo investigate brain structural and functional characteristics of three brain functional networks including default mode network (DMN), central executive network (CEN), and salience network (SN) in persistent negative symptoms (PNS) patients.MethodsWe performed an activation likelihood estimation (ALE) meta-analysis of functional connectivity (FC) studies and voxel-based morphometry (VBM) studies to detect specific structural and functional alterations of brain networks between PNS patients and healthy controls.ResultsSeventeen VBM studies and twenty FC studies were included. In the DMN, PNS patients showed decreased gray matter in the bilateral medial frontal gyrus and left anterior cingulate gyrus and a significant reduction of FC in the right precuneus. Also, PNS patients had a decrease of gray matter in the left inferior parietal lobules and medial frontal gyrus, and a significant reduction of FC in the bilateral superior frontal gyrus in the CEN. In comparison with healthy controls, PNS patients exhibited reduced gray matter in the bilateral insula, anterior cingulate gyrus, left precentral gyrus and right claustrum and lower FC in these brain areas in the SN, including the left insula, claustrum, inferior frontal gyrus and extra-nuclear.ConclusionThis meta-analysis reveals brain structural and functional imaging alterations in the three networks and the interaction among these networks in PNS patients, which provides neuroscientific evidence for more personalized treatment.Systematic Review RegistrationThe PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42022335962).

Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI.

The purpose of this study was to explore the value of resting-state magnetic resonance imaging (MRI) based on the brain extraction tool (BET) algorithm in evaluating the cranial nerve function of patients with delirium in intensive care unit (ICU). A total of 100 patients with delirium in hospital were studied, and 20 healthy volunteers were used as control. All the subjects were examined by MRI, and the images were analyzed by the BET algorithm, and the convolution neural network (CNN) algorithm was introduced for comparison. The application effects of the two algorithms were analyzed, and the differences of brain nerve function between delirium patients and normal people were explored. The results showed that the root mean square error, high frequency error norm, and structural similarity of the BET algorithm were 70.4%, 71.5%, and 0.92, respectively, which were significantly higher than those of the CNN algorithm (P < 0.05). Compared with normal people, the ReHo values of pontine, hippocampus (right), cerebellum (left), midbrain, and basal ganglia in delirium patients were significantly higher. ReHo values of frontal gyrus, middle frontal gyrus, left inferior frontal gyrus, parietal lobe, and temporal lobe and anisotropy scores (FA) of cerebellums (left), frontal lobe, temporal lobe (left), corpus callosum, and hippocampus (left) decreased significantly. The average diffusivity (MD) of medial frontal lobe, superior temporal gyrus (right), the first half of cingulate gyrus, bilateral insula, and caudate nucleus (left) increased significantly (P < 0.05). MRI based on the deep learning algorithm can effectively improve the image quality, which is valuable in evaluating the brain nerve function of delirium patients. Abnormal brain structure damage and abnormal function can be used to help diagnose delirium.

Modeling the effects of transcranial magnetic stimulation on spatial attention

Objectives. Transcranial magnetic stimulation (TMS) has been widely used to modulate brain activity in healthy and diseased brains, but the underlying mechanisms are not fully understood. Previous research leveraged biophysical modeling of the induced electric field (E-field) to map causal structure–function relationships in the primary motor cortex. This study aims at transferring this localization approach to spatial attention, which helps to understand the TMS effects on cognitive functions, and may ultimately optimize stimulation schemes. Approach. Thirty right-handed healthy participants underwent a functional magnetic imaging (fMRI) experiment, and seventeen of them participated in a TMS experiment. The individual fMRI activation peak within the right inferior parietal lobule (rIPL) during a Posner-like attention task defined the center target for TMS. Thereafter, participants underwent 500 Posner task trials. During each trial, a 5-pulse burst of 10 Hz repetitive TMS (rTMS) was given over the rIPL to modulate attentional processing. The TMS-induced E-fields for every cortical target were correlated with the behavioral modulation to identify relevant cortical regions for attentional orientation and reorientation. Main results. We did not observe a robust correlation between E-field strength and behavioral outcomes, highlighting the challenges of transferring the localization method to cognitive functions with high neural response variability and complex network interactions. Nevertheless, TMS selectively inhibited attentional reorienting in five out of seventeen subjects, resulting in task-specific behavioral impairments. The BOLD-measured neuronal activity and TMS-evoked neuronal effects showed different patterns, which emphasizes the principal distinction between the neural activity being correlated with (or maybe even caused by) particular paradigms, and the activity of neural populations exerting a causal influence on the behavioral outcome. Significance. This study is the first to explore the mechanisms of TMS-induced attentional modulation through electrical field modeling. Our findings highlight the complexity of cognitive functions and provide a basis for optimizing attentional stimulation protocols.

P049 Actigraphic rest-activity rhythms in older adults ‘at risk’ for dementia: associations with reduced cortical thickness in frontal, temporal and occipital cortices

Abstract Background Rest-activity rhythm disturbance is common in older adults ‘at risk’ for dementia. This may be an early marker of underlying disease pathology and risk of future decline. However, our understanding of how rest-activity rhythm relates to brain integrity remains unclear. Methods This study used vertex-wise analyses to examine the association between nonparametric actigraphy measures and cortical thickness in older adults ‘at risk’ for dementia. Primary measures of interest were intra-daily variability (IV), relative amplitude (RA), inter-daily stability (IS), and average activity during the least active 5-hour period (L5). Results 143 older adults ‘at risk’ for cognitive decline were included (mean age=67.41, SD=7.96). Higher IV was associated with lower cortical thickness in the right cuneus (CWP&amp;lt; 0.001), left middle frontal gyrus (CWP&amp;lt; 0.001) and lateral orbital frontal cortex (CWP=0.004). Higher L5 was linked with cortical thinning in the left superior temporal sulcus (CWP=0.004), superior middle temporal cortex (CWP=0.010) and middle temporal gyrus (CWP=0.013), as well as right inferior parietal lobe (CWP&amp;lt; 0.001). Lower IS was associated with cortical thinning in the left (CWP=0.002) and right (CWP&amp;lt; 0.001) superior frontal gyri, left superior temporal gyrus (CWP=0.043) and left post-central gyrus (CWP=0.033). Conclusions Markers of circadian rhythmicity are associated with reduced cortical thickness in frontal, temporal and occipital cortices in older adults ‘at risk’ for dementia. Future work is still required to delineate whether brain degeneration leads to altered daily rhythms and/or if circadian misalignment contributes to cognitive decline longitudinally.

Structural and Functional Alterations of Motor-Thalamus in Different Motor Subtype of Parkinson’s Disease: An Individual Study

This study aimed to investigate the structural and functional alterations occurring within bilateral premotor thalamus (mPMtha) in motor subtypes of Parkinson's disease (PD). Sixty-one individuals with instability and gait difficulty (PIGD) subtype, 60individuals with tremor-dominant (TD) subtype and 66healthy controls (HCs) participated in the study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D T1-weighted (3DT1) scans. Functional connectivity (FC) analysis and Voxel-based morphometry (VBM) analysis were performed to evaluate the function and volume of mPMtha. Additionally, correlations between motor performance and FC values, volumes were examined separately. Support vector machine (SVM) model based on FC values and thalamic volumes was conducted to assist in the clinical diagnosis of PD motor subtype. Compared toHCs and PIGD, TD subtype showed increased FC between the bilateral mPMtha and left middle occipital gyrus, left inferior parietal lobule (IPL). While PIGD subtype demonstrated decreased FC between right mPMtha and precentral gyrus (PreCG), supramarginal, IPL and superior parietal lobule. FC of bilateral mPMtha with the identified regions were significantly correlated with motor performance scores in PD patients. The SVM classification based on FC values demonstrated a high level of efficiency (AUC=0.874). The volumes of the bilateral mPMtha were indifferent among three groups. We noted distinct FC alterations of mPMtha in TD and PIGD subtypes, and these changes were correlated with motor performance. Furthermore, the machine learning based on statistically significant FC might be served as an alternative approach for automatically classifying PD motor subtypes individually.

The Sporadic Early-onset Alzheimer's Disease Signature Of Atrophy: Preliminary Findings From The Longitudinal Early-onset Alzheimer's Disease Study (LEADS) Cohort.

Magnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker. We analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n=25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n=211), and investigated the relationship of the magnitude of atrophy with cognitive impairment. The EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment. The EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD. We developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

Configuration of the action observation network depends on the goals of the observer

Observing the actions of others engages a core action observation network (AON) that includes the bilateral inferior frontal cortex (IFC), posterior superior temporal sulcus (pSTS) and inferior parietal lobule (IPL) (Caspers et al., 2010). Each region in the AON has functional properties that are heterogeneous and include representing the perceptual properties of action, predicting action outcomes and making inferences as to the goals of the actor. Critically, recent evidence shows that neural representations within the pSTS are sharpened when attending to the kinematics of the actor, such that the top-down guided attention reshapes underlying neural representations. In this study we evaluate how attention alters network connectivity within the AON as a system. Cues directed participant's attention to the goal, kinematics, or identity depicted in short action animations while brain responses were measured by fMRI. We identified those parcels within the AON with functional connectivity modulated by task. Results show that connectivity between the right pSTS and right IFC, and bilateral extended STS (STS+) were modulated during action observation such that connections were strengthened when the participant was attending to the action than goal. This finding is contrasted by the univariate results, which no univariate modulations in these brain regions except for right IFC. Using the functional networks defined by Yeo et al. (2011), we identified the parcels that are modulated by the attention to consist mainly of the fronto-parietal control network and default mode networks. These results are consistent with models of top-down feedback from executive system in the IFC to pSTS and implicates a right lateralized dual pathway model for action observation when focused on whole-body kinematics.

Differences and Changes in Cerebellar Functional Connectivity of Parkinson's Patients with Visual Hallucinations.

Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations (PD-H), even at the preclinical stage. The cerebellum has been implicated in playing a role in cognitive processes. However, the functional connectivity (FC) between the cognitive sub-regions of the cerebellum in PD patients with hallucinations needs further clarification. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from three groups (17 PD-H patients, 13 patients with Parkinson's disease not accompanied by hallucinations (PD-NH), and 26 healthy controls (HC)). The data were collected in this study to investigate the impact of cerebellar FC changes on cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machines (SVMs). We found that in the PD-H patients, there was an increase in FC within the left side of the precuneus (PCUN) compared to the HC. Additionally, there was an increase in FC within the bilateral opercular part of the inferior frontal gyrus (IFGoprec) and triangular part of the inferior frontal gyrus (IFCtriang), as well as the left side of the postcentral gyrus (PoCG), inferior parietal lobe (IPL), and PCUN compared to the PD-NH patients. In the machine learning training results, cerebellar FC has also been proven to be an effective biomarker feature, achieving a recognition rate of over 90% for PD-H. These findings indicate that the cortico-cerebellar FC in PD-H and PD-NH patients was significantly disrupted, with different patterns of distribution. The proposed pipeline offers a promising, low-cost alternative for diagnosing preclinical PD-H and may also be beneficial for other degenerative brain disorders.