Insular Regions Research Articles

Altered functional connectivity in a sensorimotor-insular network during spontaneous migraine attacks: A resting-state FMRI study

BackgroundPrevious functional magnetic resonance imaging studies have identified brain-connectivity alterations across multiple regions in people with migraine when compared to healthy controls. Few studies have focused on such changes throughout the different phases of the migraine cycle. We aimed to investigate functional connectivity during spontaneous occurring episodic migraine attacks, in comparison to interictal periods. MethodsEleven women with episodic migraine without aura underwent two sessions of resting-state fMRI, during and outside of a spontaneous migraine attack. Functional connectivity changes were assessed across canonical resting-state networks, identified by independent component analysis. Significantly altered connectivity was correlated with migraine attack symptoms. ResultsDecreased functional connectivity between subregions of the sensorimotor network (specifically, the primary somatosensory and motor cortices) and the posterior insula, bilaterally, was found during attacks. In both sessions, the functional connectivity between these regions was lower in patients who usually suffered longer attacks. DiscussionThe sensorimotor and insular regions are involved in nociceptive, autonomic, and somatosensory processing so the finding of reduced connectivity between these structures within a migraine attack is likely associated to the perception of pain and the heighten sensitivity to stimuli experienced in this disorder.

Methamphetamine enhances neural activation during anticipation of loss in the monetary incentive delay task.

Stimulants like methamphetamine (MA) affect motivated behaviors via actions on circuits mediating mood, attention, and reward. Few studies examined the effects of single doses of stimulants on reward circuits during anticipation and receipt of rewards and losses. Here, we examined the effects of MA (20mg) or placebo in a within-subject, double-blind study with healthy adults (n = 43). During 2 fMRI sessions, participants completed the monetary incentive delay task. Primary outcome measures were BOLD activation in selected regions of interest during anticipation and receipt of monetary rewards and losses. Secondary analyses included behavioral measures, whole brain analysis, and arterial spin labeling. MA produced its expected behavioral effects and increased neural activation in the ventral striatum and anterior insula during anticipation of monetary loss versus non-loss. MA did not affect activation during anticipation of gains, or during receipt of wins or losses. MA significantly reduced cerebral blood flow in the striatum and insula. The present finding that a stimulant enhances the responses of striatal and insular regions to upcoming loss suggests that this system may be sensitive to the salience of upcoming events. The finding adds to a complex body of evidence regarding the effects of stimulant drugs on neural processes during motivated behaviors.

Slow neural oscillations explain temporal fluctuations in distractibility

Human environments comprise various sources of distraction, which often occur unexpectedly in time. The proneness to distraction (i.e., distractibility) is posited to be independent of attentional sampling of targets, but its temporal dynamics and neurobiological basis are largely unknown. Brain oscillations in the theta band (3 - 8Hz) have been associated with fluctuating neural excitability, which is hypothesised here to explain rhythmic modulation of distractibility. In a pitch discrimination task (N=30) with unexpected auditory distractors, we show that distractor-evoked neural responses in the electroencephalogram and perceptual susceptibility to distraction were co-modulated and cycled approximately 3 - 5 times per second. Pre-distractor neural phase in left inferior frontal and insular cortex regions explained fluctuating distractibility. Thus, human distractibility is not constant but fluctuates on a subsecond timescale. Furthermore, slow neural oscillations subserve the behavioural consequences of a hitherto largely unexplained but ever-increasing phenomenon in modern environments - distraction by unexpected sound.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases

BackgroundNeuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases.MethodsFive hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss.ResultsAlthough NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities.ConclusionsIn participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.

Effectiveness of mindfulness-based interventions on mental, cognitive outcomes and neuroplastic changes in older adults with mild cognitive impairment: A systematic review and meta-analysis.

To evaluate the effectiveness of mindfulness-based interventions (MBIs) on mental and cognitive outcomes including, anxiety, depression, attention, memory, global cognition and neuroplastic changes in older adults with mild cognitive impairment (MCI). Systematic review and meta-analysis. A three-step search strategy was conducted on eight electronic databases, grey literature and reference lists from inception to February 2022. Randomized controlled trials (RCTs) examining MBIs on older adults with MCI were screened and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta-analysis was conducted using RevMan using a random-effect model. Narrative synthesis was performed for studies where results could not be pooled statistically. Ten RCTs were included in the review. Results suggested that right frontal parietal and left inferior temporal gyrus of the brain showed increased cortical thickness after receiving MBIs. There were significant interaction effects for global efficiency and significant interactions in the insular and gyrus regions. Functional connectivity between the posterior cingulate cortex, bilateral medial prefrontal cortex and left hippocampus were increased in participants undergoing MBIs. Nevertheless, meta-analysis showed non-significant pooled effects, favouring control groups on anxiety, depression, attention, memory and global cognition. This review suggested the potential effects of MBIs in improving cortical thickness and connectivity in regions associated with memory and attention. Nevertheless, the effects of MBIs compared to active control groups on depression, anxiety, attention, memory and global cognition are inconclusive due to the lack of studies and non-significant results. The review advocates for more rigorous studies with larger sample size and utilizing wait-list controls to evaluate the effects of MBIs. MBIs can be considered as an adjunct with other therapies to further enhance the effect on psychological and cognitive outcomes for older adults with MCI. No Patient or Public Contribution as this is a meta-analysis.

Cardiovascular and metabolic health is associated with functional brain connectivity in middle-aged and older adults: Results from the Human Connectome Project-Aging study

Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36–90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity.

Stereo-EEG localization of midline onset seizures on scalp EEG

PurposeThe objective of this study was to describe the sEEG-defined seizure onset zone (SOZ), seizure semiology, presurgical evaluations, surgical intervention and outcome in patients with midline onset noninvasive phase I monitoring. MethodsA single center sEEG database was reviewed to identify patients with seizures onset predominantly involving midline electrodes (FZ, CZ, PZ, OZ) on scalp EEG. Data abstracted included clinical factors, seizure semiology graded into lobar segmentation, imaging and electrographic findings, sEEG plan, interventions, and outcome. ResultsTwelve patients were identified (8 males, median age of sEEG 28 years) out of 100 cases of sEEG performed from January 2015-September 2019. “Frontal lobe” seizure semiology was the most common. sEEG-defined SOZ were frontal (5), diffuse (1), multifocal (1), frontal and insular (1), frontal and cingulate (1), insular (1), cingulate (1), and mesial temporal (1). CZ and/or FZ scalp EEG changes were present for all patients with SOZ involving the frontal, cingulate, and insular regions. PZ/OZ scalp involvement was present in one patient with mesial temporal SOZ. Four patients underwent a definitive resective or ablative surgery, and the remaining patients underwent a palliative intervention. Of those with follow-up information available, 8/11 had seizure reduction by ≥ 50%, including 4 with an Engel I outcome. No clinical factors were associated with outcome. ConclusionsSOZ for midline onset seizures from noninvasive phase I monitoring was most commonly in the frontal, cingulate, and insular regions. A complex cortical network between these regions may explain overlap in semiology and scalp EEG findings. While the number rendered seizure-free was limited, a significant proportion experienced a reasonably favorable outcome justifying use of sEEG to identify surgical options in these patients.

Late-life depressive symptoms and white matter structural integrity within older Black adults.

Older Black adults experience a high burden of depressive symptoms and cerebrovascular disease but the specific neurobiological substrates underlying the association between late-life depressive symptoms and brain integrity are understudied, particularly in within-group designs. Using the Center for Epidemiologic Studies Depression Scale and diffusion-tensor imaging, within-Black variation in the association between late-life depressive symptoms and white matter structural integrity was examined in 297 older Black participants without dementia that were enrolled across three epidemiological studies of aging and dementia. Linear regression models were used to test associations with DTI metrics (fractional anisotropy, trace of the diffusion tensor) as the outcomes and depressive symptoms as the predictor, while adjusting for age, sex, education, scanner, serotonin-reuptake inhibitor use, total volume of white-matter hyperintensities normalized by intracranial volume, and presence of white-matter hyperintensities at the voxel level. Higher level of self-reported late-life depressive symptoms was associated with greater diffusion-tensor trace (reduced white matter integrity) in connections between commissural pathways and contralateral prefrontal regions (superior and middle frontal/dorsolateral prefrontal cortex), association pathways connecting dorsolateral prefrontal cortex with insular, striatal and thalamic regions, and association pathways connecting the parietal, temporal and occipital lobes and the thalamus. This study demonstrated a discernable pattern of compromised white matter structural integrity underlying late-life depressive symptoms within older Black adults.

Altered longitudinal structural connectome in paediatric mild traumatic brain injury: an Advancing Concussion Assessment in Paediatrics study.

Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48 h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3 T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.

Structural integrity of the insula and emotional facial recognition performance following stroke.

The role of the human insula in facial emotion recognition is controversially discussed, especially in relation to lesion-location-dependent impairment following stroke. In addition, structural connectivity quantification of important white-matter tracts that link the insula to impairments in facial emotion recognition has not been investigated. In a case-control study, we investigated a group of 29 stroke patients in the chronic stage and 14 healthy age- and gender-matched controls. Lesion location of stroke patients was analysed with voxel-based lesion-symptom mapping. In addition, structural white-matter integrity for tracts between insula regions and their primarily known interconnected brain structures was quantified by tractography-based fractional anisotropy. Our behavioural analyses showed that stroke patients were impaired in the recognition of fearful, angry and happy but not disgusted expressions. Voxel-based lesion mapping revealed that especially lesions centred around the left anterior insula were associated with impaired recognition of emotional facial expressions. The structural integrity of insular white-matter connectivity was decreased for the left hemisphere and impaired recognition accuracy for angry and fearful expressions was associated with specific left-sided insular tracts. Taken together, these findings suggest that a multimodal investigation of structural alterations has the potential to deepen our understanding of emotion recognition impairments after stroke.

Functional Connectivity Modifications in Monoaminergic Circuits Occur in Fatigued MS Patients Treated With Fampridine and Amantadine (P10-3.008)

<h3>Objective:</h3> To investigate changes over time of fatigue severity and concomitant modifications of resting state (RS) functional connectivity (FC) in monoaminergic networks in 45 fatigued multiple sclerosis (MS) patients after different symptomatic treatments. <h3>Background:</h3> Fatigue is common and disabling in MS. Symptomatic treatments for fatigue rely on drugs reinforcing monoaminergic synaptic transmission, suggesting a role of monoaminergic network abnormalities in fatigue pathogenesis. <h3>Design/Methods:</h3> MS patients were randomly, blindly assigned to treatment with fampridine (n=15), amantadine (n=15) or placebo (n=15) and underwent clinical, neuropsychological and 3T RS fMRI at baseline (T0) and after four weeks (W4) of treatment. Fifteen matched healthy controls (HC) were acquired twice. Dopamine-, noradrenaline- and serotonin-related RS FC was derived by independent component analysis (ICA), constrained to PET atlases for dopamine, noradrenaline and serotonin transporters, obtained in HCs’ brain. Changes in modified fatigue impact scale (MFIS) score and monoaminergic-related RS FC were assessed. <h3>Results:</h3> MS patients showed baseline abnormalities <i>vs</i> HC in all three networks, with decreased monoamine-related RS FC in temporal, occipital, insular and cerebellar regions, and increased RS FC in frontal, parietal and subcortical areas. At W4, MFIS scores decreased in all patients’ groups, with no time-by-treatment interaction. At W4, fampridine and amantadine patients showed increased dopamine- and noradrenaline-related RS FC in the insular cortex, as well as increased serotonin-related RS FC in the precuneus/posterior cingulate cortex. Amantadine patients also showed increased dopamine- and noradrenaline-related RS FC in the anterior cingulate cortex (ACC). Conversely, placebo patients mostly showed increased noradrenaline-related RS FC in the precuneus and middle cingulate cortex. Fampridine and placebo groups showed trends towards significant correlations between RS FC modifications and MFIS improvements (r=−0.49: −0.52, p=0.07–0.08). <h3>Conclusions:</h3> Fatigue improved in all groups. Concomitant monoaminergic-related RS FC modifications were found in insular, ACC and parietal regions for fampridine and amantadine MS patients, and in medial parietal regions for placebo patients. <b>Disclosure:</b> Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Lamanna has nothing to disclose. Bruno Colombo has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Visual and Motor Anosognosia: shared Modality-specific Damage and convergent Disconnections in Temporo-parietal Cortex (P4-12.001)

<h3>Objective:</h3> To assess if different forms of anosognosia share different or common neural mechanisms. <h3>Background:</h3> Anosognosia, the unawareness of a neurological deficit, is a syndrome whose neural correlates are still unclear. Most theories posit that awareness deficits are encapsulated in modality-specific systems. To date, studies of anosognosia have focused on the locus of damage. However, focal lesions cause network effects far beyond the local damage. <h3>Design/Methods:</h3> We characterize and compare lesions and related structural (SDC) and functional disconnection (FDC) in a group of post-stroke Anton syndrome patients (AS) with those suffering anosognosia for hemiplegia (AHP). Sixteen AS lesions were retrieved from the literature and drawn on a standard brain template. Sixteen hemianopic visual controls (VC) were selected and their unilateral lesions were duplicated in the other hemisphere to generate synthetic bilateral lesions. The two groups were compared in terms of lesions, SDC and FDC computed using a connectome derived from a large sample of healthy controls. The resulting disconnection maps were then compared using the same approach to a group of AHP patients (n=28) and hemiplegic controls without anosognosia (HC=35). <h3>Results:</h3> Lesions in AS were cortical involving both primary and extra-striate visual cortex. In contrast, VC lesions clustered in the occipital white matter and/or the primary visual cortex. AS exhibited greater SDC of temporo-parietal and insular regions. The distribution of SDC matched the FDC of dorsal frontoparietal regions. The comparison between AS vs. AHP showed the extensive involvement of modality-specific regions (i.e., visual vs motor), but also convergent SDC of right temporo-parietal white matter and bilateral FDC of dorsal frontoparietal regions involved in attention and multi-sensory integration. <h3>Conclusions:</h3> AS depends on bilateral striate and extra-striate occipital damage, and disconnection of ventral and dorsal frontoparietal regions involved in attention control. Visual and motor anosognosia share the unique combination of modality-specific and supra-modal mechanisms over temporo-parietal cortices. <b>Disclosure:</b> Dr. Monai has nothing to disclose. Miss Palacino has nothing to disclose. Dr. Bisio has nothing to disclose. Dr. Pini has nothing to disclose. Alessandro Salvalaggio has nothing to disclose. Dr. Corbetta has nothing to disclose.

Remote effects of temporal lobe epilepsy surgery: Long-term morphological changes after surgical resection.

Epilepsy surgery is an effective treatment for drug-resistant patients. However, how different surgical approaches affect long-term brain structure remains poorly characterized. Here, we present a semiautomated method for quantifying structural changes after epilepsy surgery and compare the remote structural effects of two approaches, anterior temporal lobectomy (ATL), and selective amygdalohippocampectomy (SAH). We studied 36 temporal lobe epilepsy patients who underwent resective surgery (ATL = 22, SAH = 14). All patients received same-scanner MR imaging preoperatively and postoperatively (mean 2 years). To analyze postoperative structural changes, we segmented the resection zone and modified the Advanced Normalization Tools (ANTs) longitudinal cortical pipeline to account for resections. We compared global and regional annualized cortical thinning between surgical treatments. Across procedures, there was significant cortical thinning in the ipsilateral insula, fusiform, pericalcarine, and several temporal lobe regions outside the resection zone as well as the contralateral hippocampus. Additionally, increased postoperative cortical thickness was seen in the supramarginal gyrus. Patients treated with ATL exhibited greater annualized cortical thinning compared with SAH cases (ATL: -0.08 ± 0.11 mm per year, SAH: -0.01 ± 0.02 mm per year, t = 2.99, P = 0.006). There were focal postoperative differences between the two treatment groups in the ipsilateral insula (P = 0.039, corrected). Annualized cortical thinning rates correlated with preoperative cortical thickness (r = 0.60, P < 0.001) and had weaker associations with age at surgery (r = -0.33, P = 0.051) and disease duration (r = -0.42, P = 0.058). Our evidence suggests that selective procedures are associated with less cortical thinning and that earlier surgical intervention may reduce long-term impacts on brain structure.

Longitudinal free-water changes in dementia with Lewy bodies (P8-11.007)

<h3>Objective:</h3> To characterize longitudinal diffusion microstructural changes in individuals with dementia with Lewy bodies (DLB). <h3>Background:</h3> Diffusion-weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior DLB studies focused on white matter or voxel-based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. <h3>Design/Methods:</h3> dMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12 or 24 months. Free-water (FW) and FW-corrected fractional anisotropy (FA_T) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest in Montreal Neurological Institute space. Primary outcomes were differences in FW and FA_T between baseline and 12 or 24 months. <h3>Results:</h3> We identified 23 individuals with DLB from baseline to 12 months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24 months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time-points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (<i>p</i>&lt;0.05). We found significant differences in FW, but not FA_T, from baseline to 12 months. Significant increases in FW at both time-points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (p&lt;0.05). We found more widespread microstructural changes from baseline to 24 months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (p&lt;0.05). We found decreased FA_T from baseline to 24 months in the cerebellar and superior occipital regions (<i>p</i>&lt;0.01). <h3>Conclusions:</h3> Longer follow-up at 24 months identified broader networks of free-water changes in individuals with DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB. <b>Disclosure:</b> Dr. Chiu has received research support from NIH/NIA. Mr. Chen has nothing to disclose. Dr. Wang has nothing to disclose. The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. David Vaillancourt has received personal compensation for serving as an employee of Automated Imaging Diagnostics. David Vaillancourt has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. The institution of David Vaillancourt has received research support from NIH. David Vaillancourt has received intellectual property interests from a discovery or technology relating to health care.

Assessment of Risk Factors and Clinical Importance of Enlarged Perivascular Spaces by Whole-Brain Investigation in the Multi-Ethnic Study of Atherosclerosis

Enlarged perivascular spaces (ePVSs) have been associated with cerebral small-vessel disease (cSVD). Although their etiology may differ based on brain location, study of ePVSs has been limited to specific brain regions; therefore, their risk factors and significance remain uncertain. Toperform a whole-brain investigation of ePVSs in a large community-based cohort. This cross-sectional study analyzed data from the Atrial Fibrillation substudy of the population-based Multi-Ethnic Study of Atherosclerosis. Demographic, vascular risk, and cardiovascular disease data were collected from September 2016 to May 2018. Brain magnetic resonance imaging was performed from March 2018 to July 2019. The reported analysis was conducted between August and October 2022. A total of 1026 participants with available brain magnetic resonance imaging data and complete information on demographic characteristics and vascular risk factors were included. Enlarged perivascular spaces were quantified using a fully automated deep learning algorithm. Quantified ePVS volumes were grouped into 6 anatomic locations: basal ganglia, thalamus, brainstem, frontoparietal, insular, and temporal regions, and were normalized for the respective regional volumes. The association of normalized regional ePVS volumes with demographic characteristics, vascular risk factors, neuroimaging indices, and prevalent cardiovascular disease was explored using generalized linear models. In the 1026 participants, mean (SD) age was 72 (8) years; 541 (53%) of the participants were women. Basal ganglia ePVS volume was positively associated with age (β = 3.59 × 10-3; 95% CI, 2.80 × 10-3 to 4.39 × 10-3), systolic blood pressure (β = 8.35 × 10-4; 95% CI, 5.19 × 10-4 to 1.15 × 10-3), use of antihypertensives (β = 3.29 × 10-2; 95% CI, 1.92 × 10-2 to 4.67 × 10-2), and negatively associated with Black race (β = -3.34 × 10-2; 95% CI, -5.08 × 10-2 to -1.59 × 10-2). Thalamic ePVS volume was positively associated with age (β = 5.57 × 10-4; 95% CI, 2.19 × 10-4 to 8.95 × 10-4) and use of antihypertensives (β = 1.19 × 10-2; 95% CI, 6.02 × 10-3 to 1.77 × 10-2). Insular region ePVS volume was positively associated with age (β = 1.18 × 10-3; 95% CI, 7.98 × 10-4 to 1.55 × 10-3). Brainstem ePVS volume was smaller in Black than in White participants (β = -5.34 × 10-3; 95% CI, -8.26 × 10-3 to -2.41 × 10-3). Frontoparietal ePVS volume was positively associated with systolic blood pressure (β = 1.14 × 10-4; 95% CI, 3.38 × 10-5 to 1.95 × 10-4) and negatively associated with age (β = -3.38 × 10-4; 95% CI, -5.40 × 10-4 to -1.36 × 10-4). Temporal region ePVS volume was negatively associated with age (β = -1.61 × 10-2; 95% CI, -2.14 × 10-2 to -1.09 × 10-2), as well as Chinese American (β = -2.35 × 10-1; 95% CI, -3.83 × 10-1 to -8.74 × 10-2) and Hispanic ethnicities (β = -1.73 × 10-1; 95% CI, -2.96 × 10-1 to -4.99 × 10-2). In this cross-sectional study of ePVSs in the whole brain, increased ePVS burden in the basal ganglia and thalamus was a surrogate marker for underlying cSVD, highlighting the clinical importance of ePVSs in these locations.

Forest Fragmentation and Landscape Connectivity Changes in Ecuadorian Mangroves: Some Hope for the Future?

This study investigates the impact of fragmentation on Ecuador’s coastal mangrove forests. Fragmentation is identified as a primary cause of aquatic ecosystem degradation. We analyzed the relationship between habitat loss, fragmentation, and mangrove connectivity through a multitemporal approach using Global Mangrove Watch and fragmentation and connectivity metrics. The terrain was divided into 10 km2 hexagons, and six fragmentation metrics were calculated. A Getis–Ord Gi* statistical analysis was used to identified areas with the best and worst conservation status, while connectivity analyses were performed for a generic species with a 5 km dispersion. Findings revealed widespread mangrove fragmentation in Ecuador, with geographical differences between the insular region (Galapagos) and the mainland coast. Minimal loss or even expansion of mangrove forests in areas like the Galapagos Islands contrasted with severe fragmentation along the mainland coast. Transformation of forests into fisheries, mainly prawn factories, was the primary driver of change, while only a weak correlation was observed between mangrove fragmentation and conversion to agriculture, which accounts for less than 15% of all deforestation in Ecuador. Fragmentation may increase or decrease depending on the management of different deforestation drivers and should be considered in large-scale mangrove monitoring. Focusing only on mangrove deforestation rates in defining regional conservation priorities may overlook the loss of ecosystem functions and fragmentation.

292 Hyperorality in Frontotemporal Dementia: Psychiatric and Neural Correlates Across the Disease Course

OBJECTIVES/GOALS: To describe cognitive and psychiatric symptom profiles of individuals with bvFTD and hyperorality. We test two hypotheses: (1) individuals with hyperorality show more severe psychiatric profiles and (2) neuroanatomic correlates of hyperorality in advanced bvFTD differ from those with early bvFTD. METHODS/STUDY POPULATION: Participants were enrolled in ALLFTD–a multi-site longitudinal study in FTD. We selected the 354 participants who had a primary clinical diagnosis of bvFTD, 344 of whom had data on hyperorality. Each participant underwent extensive clinical interviews and examinations, structural neuroimaging, and blood sampling. Five anatomic regions of interest were identified and analyzed based on previously identified neuroanatomic correlates of hyperorality. Differences in participant characteristics and clinical outcomes were compared using t-tests for continuous variables and Pearsonχ2 tests for categorical variables. Linear multivariate regression controlling for age and total intracranial volume (TIV) was used to examine associations between atrophy in regions of interest and hyperorality status. RESULTS/ANTICIPATED RESULTS: Early-stage participants with hyperorality had poorer self-monitoring, empathic concern, and perspective taking as well as higher CDR behavioral subscale scores compared to those without hyperorality. Advanced stage participants with hyperorality had higher scores on the Social Behavior Observer Checklist compared to those without hyperorality. Early-stage participants with hyperorality displayed higher rates of ritualistic/compulsive behavior and motor disturbance. Advanced stage participants had higher rates of apathy, ritualistic/compulsive behavior, anxiety, and elation. In the advanced stage participants, hyperorality was associated with atrophy in the right dorsal striatum, the right ventral striatum, and the right insula cortex. DISCUSSION/SIGNIFICANCE: Hyperorality emerges early and is accompanied by neuropsychiatric symptoms prior to significant neurodegeneration. Overtime, participants with hyperorality develop more psychiatric symptoms as well as atrophy in striatal and insular brain regions. Our findings suggest a role for novel interventions like non-invasive brain stimulation.

Embryology and Clinical Development of the Human Olfactory System

AbstractThe olfactory system is unique as a special sensory system in its developmental neuroanatomy and function. Neonatal olfactory reflexes can be detected in the fetus from 30 weeks gestation and can be tested in term and preterm neonates and older children. Most efferent axons from the olfactory bulb terminate in the anterior olfactory nucleus within the olfactory tract, with secondary projections to the amygdala, hypothalamus, hippocampus, and entorhinal cortex (parahippocampal gyrus), with tertiary projections also to the insula and other cortical regions. The olfactory bulb and tract incorporate an intrinsic thalamic equivalent. The olfactory bulb may be primary in generating olfactory auras in some cases of temporal lobe epilepsy. Developmental malformations may involve the olfactory bulb and tract, isolated or as part of complex cerebral malformations and genetic syndromes. Primary neural tumors may arise in the olfactory bulb or nerve. Impaired olfaction occurs in neonatal hypoxic/ischemic and some metabolic encephalopathies. Loss of sense of smell are early symptoms in some neurodegenerative diseases and in some viral respiratory diseases including coronavirus disease 2019. Testing cranial nerve I is easy and reliable at all ages, and is recommended in selected neonates with suspected brain malformations or encephalopathy.

The influence of high worry on static and dynamic insular functional connectivity.

Worry is a form of repetitive negative thought. High worry-proneness is one risk factor leading to anxiety disorder. Several types of research indicated that anxiety disorder was highly associated with disrupted interoception. The insula is consistently considered to play a key role in interoception. However, the relationship between worry and the interoception network is poorly investigated in worry-prone individuals. Thus, it is essential to identify the neural characteristic of high worry-proneness subjects. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited and underwent magnetic resonance imaging scanning. Six subregions of insula were chosen as regions of interest. Then, seed-based static and dynamic functional connectivity were calculated. Increased static functional connectivity was observed between the ventral anterior insula and inferior parietal lobule in HWP compared to LWP. Decreased static functional connectivity was found between the left ventral anterior insula and the pregenual anterior cingulate cortex. Decreased dynamic functional connectivity was also shown between the right posterior insula and the inferior parietal lobule in HWP. Moreover, a post-hoc test exploring the effect of changed function within the insular region confirmed that a significant positive relationship between static functional connectivity (ventral anterior insula-inferior parietal lobule) and dynamic functional connectivity (posterior insula-inferior parietal lobule) in LWP but not in HWP. Our results might suggest that deficient insular function may be an essential factor related to high worry in healthy subjects.

Automatic adaptive emotion regulation is associated with lower emotion-related activation in the frontoparietal cortex and other cortical regions with multi-componential organization.

Although some researchers consider automatic adaptive emotion regulation to be an automatized strategy whereas others consider it to be implicit disengagement of deliberative process, to date, its neural correlates have been poorly investigated. In addition, the valence specificity of automatic adaptive emotion regulation and levels of activation relative to the neutral condition are controversial; the former is relevant to the attribution of resilient emotion regulation to positivity bias or emotional stability, and the latter to determining whether regulation is based on emotion-specific or emotion-non-specific processes. In this functional magnetic resonance imaging (fMRI) study, we presented positive and negative emotional pictures to healthy young participants and investigated the neural correlates of automatic adaptive emotion regulation in spontaneous emotional response. A significant negative trait effect (i.e., regression coefficient) on activation was identified both for positive and negative emotional responses in various cortical regions. A cluster analysis identified three clusters among these regions based on the valence specificity of the trait effect and level of activation relative to neutral stimuli. Cluster 1 included regions in the sensorimotor cortex characterized by negative emotion-specific decreases in activation relative to neutral stimuli in adaptive individuals. Cluster 2 included several cortical regions including the bilateral dorsal executive network, anterior cingulate, and inferior frontal gyrus, which were characterized by valence-independent decreases in activation in adaptive individuals. Cluster 3 included the bilateral ventrolateral and dorsomedial prefrontal cortices, right insula, and other posterior regions, which were characterized by increased activation for negative stimuli in non-adaptive individuals. These findings support the assumption that automatic adaptive emotion regulation involves the implicit disengagement of deliberative process and suggest the relevance of different cortical networks to the potential emotion- and valence-specificity of adaptive regulation.