Posterior Frontal Cortex Research Articles

Hyperactivity and altered functional connectivity of the ventral striatum in schizophrenia compared with bipolar disorder: A resting state fMRI study

BackgroundSchizophrenia patients frequently present with structural and functional abnormalities of the ventral striatum (VS). Methodswe examined basal activation state and functional connectivity (FC) in four subregions of the bilateral ventral striatum: left inferior ventral striatum (VSi_L), left superior ventral striatum(VSs_L), right inferior ventral striatum(VSi_R), and right superior ventral striatum(VSs_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients (SCH), 57 bipolar disorder (BD) patients, and 26 healthy controls (HCs). ResultsThe schizophrenia group exhibited greater fALFF in bilateral VS subregions compared to BD and HC groups as well as greater FC between the bilateral VSi and multiple brain regions, including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. Moreover, the fALFF values of the bilateral ventral striatum were positively correlated with the severity of positive symptoms. We also found the functional connectivity between the bilateral inferior ventral striatum and some brain regions aforementioned were positively correlated with the severity of negative symptoms. ConclusionThese findings confirm a crucial contribution of ventral striatum dysfunction, especially of the bilateral VSi in schizophrenia. Functionally dissociated regions of the ventral striatum are differentially disturbed in schizophrenia.

Clinicopathologic and Neuroimaging Correlations of Nonverbal Oral Apraxia in Patients With Neurodegenerative Disease.

Nonverbal oral apraxia (NVOA) is the inability to plan, sequence, and execute voluntary oromotor movements in the absence of weakness. In the context of neurodegenerative disease, it remains unclear whether it is linked to a specific underlying pathologic, clinical, or neuroimaging finding. Thus, we aimed to assess the clinicopathologic and neuroimaging associations of NVOA. We conducted a retrospective study of autopsy-confirmed patients previously assessed through an NVOA evaluation tool with a previously published cutpoint to screen for NVOA. We compared demographic and clinical characteristics and postmortem pathology between those who developed NVOA and those who did not. We also compared clinicopathologic characteristics in mild vs greater than mild NVOA and early vs late-emerging NVOA. SPM12 was used to assess patterns of gray matter loss in NVOA vs non-NVOA with age and sex included as covariates. A total of 104 patients (median age at symptom onset 63 years, 43% female) were included in the study. 63 (60.6%) developed NVOA. NVOA appeared at a median of 4.3 years from symptom onset. 29% developed NVOA within the first 3 years. Primary progressive apraxia of speech and the nonfluent variant of primary progressive aphasia were the most common baseline diagnoses in the NVOA group while progressive supranuclear palsy (PSP) syndrome and logopenic progressive aphasia (LPA) were the most common in patients without NVOA. Atrophy of the left lateral and medial posterior frontal cortex was related to NVOA. The most common pathologies associated with NVOA were PSP (36.5%) and corticobasal degeneration (CBD) (33.3%). In patients without NVOA, PSP (26.8%) and other pathologies (26.8%) were the most frequent. 11% of patients with NVOA had persistently mild NVOA and were more likely to have baseline diagnoses of LPA, PSP syndrome, or semantic dementia. The most frequent pathologies in this group were Alzheimer disease and PSP. The pathologic associations of greater than mild NVOA were CBD and PSP. NVOA is present in several clinical syndromes. It is most associated with PSP and CBD. NVOA is a manifestation of left lateral and medial posterior frontal cortex damage rather than a particular pathology.

The relationship between SV2A levels, neural activity, and cognitive function in healthy humans: A [11C]UCB-J PET and fMRI study

Abstract Synaptic terminal density is thought to influence cognitive function and neural activity, yet its role in cognition has not been explored in healthy humans. We examined these relationships using [11C]UCB-J positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in 25 healthy adults performing cognitive function tasks in the scanner. We found a significant positive association between synaptic terminal density, indicated by [11C]UCB-J PET distribution volume ratio (DVRcs), and neural activity during task switching (PLS-CA, second canonical component, r = 0.63, p = 0.043) with the thalamus-putamen data positively contributing to this relationship (PLS-CA loading 0.679, exploratory Pearson’s correlation r = 0.42, p = 0.044, uncorrected). Furthermore, synaptic terminal density predicted switch cost (PLS-R, R2 = 0.45, RMSE = 0.06, p = 0.022), with DVRcs negatively correlating with switch cost in key brain regions including the dorsolateral prefrontal cortex and posterior frontal cortex. Conversely, no significant relationships were observed between [11C]UCB-J DVRcs and neural activity or performance measures in the N-back working memory task, suggesting interindividual differences in synaptic terminal density may be more closely related to some cognitive functions and not others.

Pick's Disease Presenting as Tremulous Parkinsonism with Limited Levodopa Response-A Rare Cause of Corticobasal Syndrome.

Corticobasal syndrome is a clinical diagnosis and common pathological causes are corticobasal degeneration, progressive supranuclear palsy and Alzheimer's disease. We would like to highlight a rare but important differential of corticobasal syndrome. A 78-year-old female had a 4-year history of predominantly right-hand rest tremor, worsening of handwriting but no change in cognition. The clinical examination showed right upper limb postural and kinetic tremor, mild wrist rigidity and reduced amplitude of right-sided finger tapping. She was initially diagnosed as idiopathic Parkinson's disease. Five years after onset of symptoms, she demonstrated bilateral myoclonic jerks and right upper limb dystonic posturing. She could not copy movements with the right hand. The magnetic resonance imaging (MRI) revealed disproportionate atrophy in the parietal lobes bilaterally. The clinical diagnosis was changed to probable corticobasal syndrome. She passed away 11 years from onset of symptoms at the age of 85 years. She underwent a post-mortem. The anterior and posterior frontal cortex, anterior cingulate, temporal neocortex, hippocampus and amygdaloid complex demonstrated considerable tau-related pathology consisting of a dense background of neuropil threads, and rounded, paranuclear neuronal inclusions consistent with Pick bodies. The immunostaining for three microtubule binding domain repeats (3R) tau performed on sections from the frontal and temporal lobes, basal ganglia and midbrain highlighted several inclusions whilst no 4R tau was observed. She was finally diagnosed with Pick's disease. Pick's disease can rarely present with clinical features of corticobasal syndrome.

Change in Resting-State Functional Connectivity Following Working Memory Training in Individuals With Repetitive Negative Thinking

BackgroundRepetitive negative thinking (RNT) symptoms, which are characterized by pervasive, uncontrollable negative thoughts, are common in individuals with mood, anxiety, and traumatic stress disorders. Inability to regulate the contents of working memory is a hypothesized etiological factor in RNT, which suggests that training to improve working memory may be beneficial. This study examined the effects of working memory training on resting-state functional connectivity (rsFC) in individuals with elevated RNT and whether such changes would be associated with clinical improvement. MethodsWe conducted a secondary analysis of pre-post resting-state data collected as part of a randomized controlled trial (NCT04912089) of working memory training interventions (n = 42) compared with a waitlist control group (n = 23). We hypothesized that individuals who completed training would show increased rsFC between the 2 key intrinsic connectivity networks—the default mode network (posterior cingulate cortex) and the frontoparietal network (dorsolateral prefrontal cortex). We explored whether the magnitude of rsFC change was associated with change in RNT symptom severity. ResultsrsFC increased between the posterior cingulate cortex and regions including the frontal and parietal cortex in the training group compared with the waitlist group. Increased connectivity between the posterior cingulate cortex and superior frontal cortex was associated with RNT symptom reduction. ConclusionsThese data provide evidence that working memory training can modulate neural circuitry at rest in individuals with RNT. Results are consistent with accounts of working memory training effects on large-scale neurocircuitry changes and suggest that these changes may contribute to clinical promise of this type of intervention on transdiagnostic RNT symptoms.

Interpretable deep learning model for major depressive disorder assessment based on functional near-infrared spectroscopy

BackgroundMajor depressive disorder (MDD) affects a substantial number of individuals worldwide. New approaches are required to improve the diagnosis of MDD, which relies heavily on subjective reports of depression-related symptoms. AimEstablish an objective measurement and evaluation of MDD. MethodsFunctional near-infrared spectroscopy (fNIRS) was used to investigate the brain activity of MDD patients and healthy controls (HCs). Leveraging a sizeable fNIRS dataset of 263 HCs and 251 patients with MDD, including mild to moderate MDD (mMDD; n = 139) and severe MDD (sMDD; n = 77), we developed an interpretable deep learning model for screening MDD and staging its severity. ResultsThe proposed deep learning model achieved an accuracy of 80.9% in diagnostic classification and 78.6% in severity staging for MDD. We discerned five channels with the most significant contribution to MDD identification through Shapley additive explanations (SHAP), located in the right medial prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, and left posterior superior frontal cortex. The findings corresponded closely to the features of haemoglobin responses between HCs and individuals with MDD, as we obtained a good discriminative ability for MDD using cortical channels that are related to the disorder, namely the frontal and temporal cortical channels with areas under the curve of 0.78 and 0.81, respectively. ConclusionOur study demonstrated the potential of integrating the fNIRS system with artificial intelligence algorithms to classify and stage MDD in clinical settings using a large dataset. This approach can potentially enhance MDD assessment and provide insights for clinical diagnosis and intervention.

Regional correlation analysis between neuronal metabolism and synaptic density using [18F]FDG and [11C]UCB‐J

AbstractBackgroundNeuronal hypometabolism measured with [18F]FDG PET scans can be used to identify neurodegeneration as part of the AT(N) (amyloid, tau, neurodegeneration) framework in AD. PET imaging of synaptic vesicle glycoprotein SV2A using [11C]UCB‐J provides an index of synaptic density, which has been shown to decrease during neurodegeneration. The purpose of this study was to examine the regional relationship between neuronal metabolism and synaptic density in participants across the continuum of AD‐related pathology.MethodParticipants were recruited from the Wisconsin ADRC and the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study. A subset of 13 participants (Table 1) were selected who had completed cognitive testing, structural MR imaging, and PET imaging with the following: [11C]PiB centiloid (CL) for amyloid +/‐ status, [18F]MK‐6240 SUVR for tau +/‐ status, [11C]UCB‐J DVR for regional synaptic density burden, and [18F]FDG SUVR for regional glucose metabolism. UCB‐J and FDG analysis used a whole cerebellum reference region; PiB and MK‐6240 analysis used cerebellar GM reference regions. Inter‐tracer (UCB‐J/FDG) correlations were performed in Freesurfer‐defined bilateral Braak‐associated ROIs (Medial Temporal Lobe [MTL]: entorhinal cortex, hippocampus, and amygdala; Ventral Temporal Lobe [VTL]: fusiform, lingual, and inferior temporal gyri), signature regions of hypometabolism in AD (posterior cingulate, parietal, and frontal cortices) and a region with only marginal hypometabolism in AD (occipital cortex). Associations were determined using Pearson correlations (r).ResultAll ROIs demonstrate a positive association between FDG SUVR and UCB‐J DVR, with r > 0.7 and p < 0.01 (Figure 1). The occipital, frontal, and posterior cingulate cortices demonstrate the strongest correlations (r = 0.84, 0.83, and 0.81, respectively).ConclusionIn cognitively impaired and unimpaired participants showing varying degrees of ß‐amyloid and neurofibrillary tau burden, strong positive correlations are observed in regions associated with AD tau pathology and hypometabolism. Correlations are also observed in regions not typically associated with hypometabolism. This suggests that a relationship may exist between synaptic density and neuronal metabolism in the presence of AD neuropathology.

Regional correlation analysis between neuronal metabolism and synaptic density using [18F]FDG and [11C]UCB‐J

AbstractBackgroundNeuronal hypometabolism measured with [18F]FDG PET scans can be used to identify neurodegeneration as part of the AT(N) (amyloid, tau, neurodegeneration) framework in AD. PET imaging of synaptic vesicle glycoprotein SV2A using [11C]UCB‐J provides an index of synaptic density, which has been shown to decrease during neurodegeneration. The purpose of this study was to examine the regional relationship between neuronal metabolism and synaptic density in participants across the continuum of AD‐related pathology.MethodParticipants were recruited from the Wisconsin ADRC and the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study. A subset of 13 participants (Table 1) were selected who had completed cognitive testing, structural MR imaging, and PET imaging with the following: [11C]PiB centiloid (CL) for amyloid +/‐ status, [18F]MK‐6240 SUVR for tau +/‐ status, [11C]UCB‐J DVR for regional synaptic density burden, and [18F]FDG SUVR for regional glucose metabolism. UCB‐J and FDG analysis used a whole cerebellum reference region; PiB and MK‐6240 analysis used cerebellar GM reference regions. Inter‐tracer (UCB‐J/FDG) correlations were performed in Freesurfer‐defined bilateral Braak‐associated ROIs (Medial Temporal Lobe [MTL]: entorhinal cortex, hippocampus, and amygdala; Ventral Temporal Lobe [VTL]: fusiform, lingual, and inferior temporal gyri), signature regions of hypometabolism in AD (posterior cingulate, parietal, and frontal cortices) and a region with only marginal hypometabolism in AD (occipital cortex). Associations were determined using Pearson correlations (r).ResultAll ROIs demonstrate a positive association between FDG SUVR and UCB‐J DVR, with r > 0.7 and p < 0.01 (Figure 1). The occipital, frontal, and posterior cingulate cortices demonstrate the strongest correlations (r = 0.84, 0.83, and 0.81, respectively).ConclusionIn cognitively impaired and unimpaired participants showing varying degrees of β‐amyloid and neurofibrillary tau burden, strong positive correlations are observed in regions associated with AD tau pathology and hypometabolism. Correlations are also observed in regions not typically associated with hypometabolism. This suggests that a relationship may exist between synaptic density and neuronal metabolism in the presence of AD neuropathology.

Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

Where in the brain do internally generated and externally presented visual information interact?

Conscious experiences normally result from the flow of external input into our sensory systems. However, we can also create conscious percepts independently of sensory stimulation. These internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts. Consequently, mental imagery is often referred to as “seeing in the mind’s eye”. While the neural basis of imagery has been widely studied, the interaction between internal and external sources of visual information has received little interest. Here we examined this question by using fMRI to record brain activity of healthy human volunteers while they were performing visual imagery that was distracted with a concurrent presentation of a visual stimulus. Multivariate pattern analysis (MVPA) was used to identify the brain basis of this interaction. Visual imagery was reflected in several brain areas in ventral temporal, lateral occipitotemporal, and posterior frontal cortices, with a left-hemisphere dominance. The key finding was that imagery content representations in the left lateral occipitotemporal cortex were disrupted when a visual distractor was presented during imagery. Our results thus demonstrate that the representations of internal and external visual information interact in brain areas associated with the encoding of visual objects and shapes.

The neuropathological landscape of Hispanic and non-Hispanic White decedents with Alzheimer disease

Despite the increasing demographic diversity of the United States’ aging population, there remain significant gaps in post-mortem research investigating the ethnoracial heterogeneity in the neuropathological landscape of Alzheimer Disease (AD). Most autopsy-based studies have focused on cohorts of non-Hispanic White decedents (NHWD), with few studies including Hispanic decedents (HD). We aimed to characterize the neuropathologic landscape of AD in NHWD (n = 185) and HD (n = 92) evaluated in research programs across three institutions: University of California San Diego, University of California Davis, and Columbia University. Only persons with a neuropathologic diagnosis of intermediate/high AD determined by NIA Reagan and/or NIA-AA criteria were included. A frequency-balanced random sample without replacement was drawn from the NHWD group using a 2:1 age and sex matching scheme with HD. Four brain areas were evaluated: posterior hippocampus, frontal, temporal, and parietal cortices. Sections were stained with antibodies against Aβ (4G8) and phosphorylated tau (AT8). We compared the distribution and semi-quantitative densities for neurofibrillary tangles (NFTs), neuropil threads, core, diffuse, and neuritic plaques. All evaluations were conducted by an expert blinded to demographics and group status. Wilcoxon’s two-sample test revealed higher levels of neuritic plaques in the frontal cortex (p = 0.02) and neuropil threads (p = 0.02) in HD, and higher levels of cored plaques in the temporal cortex in NHWD (p = 0.02). Results from ordinal logistic regression controlling for age, sex, and site of origin were similar. In other evaluated brain regions, semi-quantitative scores of plaques, tangles, and threads did not differ statistically between groups. Our results demonstrate HD may be disproportionately burdened by AD-related pathologies in select anatomic regions, particularly tau deposits. Further research is warranted to understand the contributions of demographic, genetic, and environmental factors to heterogeneous pathological presentations.

A neurophysiological approach to the distinction between motor and cognitive skills: a functional magnetic resonance imaging study.

This study investigated the neurophysiological differences underpinning motor and cognitive skills by measuring the brain activity via functional magnetic resonance imaging. Twenty-five healthy adults (11 women, 25.8 ± 3.5 years of age) participated in the study. We developed three types of tasks, namely, simple motor task (SMT), complex motor task (CMT), and cognitive task (CT), using two-dimensional images of Gomoku, a traditional game known as five in a row. When shown the stimulus, participants were instructed to identify the best spot to win the game and to perform motor imagery of placing the stone for the SMT and CMT but not for the CT. Accordingly, we found significant activation from the CMT minus SMT contrast in the dorsolateral prefrontal cortex, posterior parietal cortex, precentral gyrus, and superior frontal cortex, which reflected increased visuospatial attention, working memory, and motor planning. From the CT minus SMT contrast, we observed significant activation in the left caudate nucleus, right medial prefrontal cortex, and right primary somatosensory cortex, responsible for visuospatial working memory, error detection, and cognitive imagery, respectively. The present findings indicate that adopting a conventional classification of cognitive and motor tasks focused on the extent of decision making and motor control involved in task performance might not be ideal.

Hierarchical categorization learning is associated with representational changes in the dorsal striatum and posterior frontal and parietal cortex.

Learning and recognition can be improved by sorting novel items into categories and subcategories. Such hierarchical categorization is easy when it can be performed according to learned rules (e.g., "if car, then automatic or stick shift" or "if boat, then motor or sail"). Here, we present results showing that human participants acquire categorization rules for new visual hierarchies rapidly, and that, as they do, corresponding hierarchical representations of the categorized stimuli emerge in patterns of neural activation in the dorsal striatum and in posterior frontal and parietal cortex. Participants learned to categorize novel visual objects into a hierarchy with superordinate and subordinate levels based on the objects' shape features, without having been told the categorization rules for doing so. On each trial, participants were asked to report the category and subcategory of the object, after which they received feedback about the correctness of their categorization responses. Participants trained over the course of a one-hour-long session while their brain activation was measured using functional magnetic resonance imaging. Over the course of training, significant hierarchy learning took place as participants discovered the nested categorization rules, as evidenced by the occurrence of a learning trial, after which performance suddenly increased. This learning was associated with increased representational strength of the newly acquired hierarchical rules in a corticostriatal network including the posterior frontal and parietal cortex and the dorsal striatum. We also found evidence suggesting that reinforcement learning in the dorsal striatum contributed to hierarchical rule learning.

LIVING IN A DOLL HOUSE: A CASE REPORT AND LITERATURE REVIEW OF REDUPLICATIVE PARAMNESIA

Introduction Reduplicative paramnesia (RP) is a very rare content-specific delusional misidentification syndrome (DMS). RP entails the delusion that a place, an object, or an event has been duplicated or exists in two different places at the same time. RP is thought to result from an organic rather than psychiatric cause distinguishing it from other DMS. It has been suggested that damage to the right frontal and temporal lobe plays a crucial role, although other areas involved in visuospatial processing have also been reported.ObjectivesThe aim of this study is to review the literature and report a clinical case of RP.MethodsWe describe a case of an 81 year old woman admitted in a Neurology ward, with a 2 week clinical presentation of temporo-spatial disorientation, behavioural changes, persecutory delusions and reduplicative paramnesia phenomena concerning her house. She had previous history of a stroke 3 years prior to admission and, about one year before, the patient also started to present cognitive decline in the context of Parkinson’s dementia. One month before admission, treatment with Rotigotine was started and later suspended when the aforementioned clinical manifestations started. Upon admission it was diagnosed an urinary tract infection and treatment with antibiotics was started. Two days afterwards, the patient recovered orientation and her usual behaviour, but persecutory delusions and RP persisted. She then started treatment with low dose Olanzapine. Following 2 weeks of treatment the psychotic symptoms fully remitted, including RP.ResultsWe underline CT-scan and EEG relevant findings upon admission. In the CT-scan sequelar lesions in left frontoparietal junction, right posterior frontal cortex, left inferior occipital cortex, bilateral cerebellar hemispheres, left caudate nucleae and thalamus were identified. The EEG showed a preserved posterior alpha rhythm associated with slow discontinuous right temporal and mainly left parieto-temporo-occipital activity, indicating dysfunction in these locations.ConclusionsIn line with literature our patient had lesions in the right frontal and temporal lobe. She also presented lesions in other areas involved with visuospatial processing. Particularly the involvement of the left hemisphere reported in our case seems to be an exception. Other factors potentially played a role triggering this episode, namely the cognitive compromise due to dementia interposed with infectious disease, and the rotigotine treatment as well. Another aspect worth mentioning in our case was the remission of symptoms with the use of Olanzapine, even though only a few cases in literature have fully remitted with treatment with antipsychotics.Disclosure of InterestNone Declared

Abstract Number ‐ 266: Focal Cerebral CNS Vasculitis due to SARS‐CoV‐2 Infection

Introduction Several neurological manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, including anosmia, encephalopathy, and stroke, have been reported. We report a case of a 42‐year‐old man presenting with ischemic stroke due to cerebral vasculitis in the setting of SARS‐CoV‐2 infection. Methods Case report Results A 42‐year‐old man, recently diagnosed with SARS‐CoV‐2 infection, presented with nonfluent aphasia and right‐sided hemiparesis that started five hours prior. Neurological examination revealed nonfluent aphasia, right‐sided facial palsy, and hemiparesis. Computed tomography (CT) of the head showed left‐sided caudate infarct and early ischemic changes in the left putamen. CT angiography (CTA) revealed occlusion of the proximal left M1 segment. Patient’s symptoms rapidly improved and mechanical thrombectomy was not pursued. Patient was started on dual antiplatelet therapy with aspirin and clopidogrel. Magnetic resonance imaging (MRI) of the brain showed acute infarcts in the left posterior parietal, lentiform nucleus, and frontal cortex. CT of the chest revealed bilateral subsegmental pulmonary emboli. Patient was discharged on apixaban and atorvastatin daily, with mild residual aphasia. A month later, the patient returned with dysarthria and right‐sided paresthesia that began three hours prior. CTA showed severe left proximal M1 stenosis involving a longer segment. He was started on vasopressor. Symptoms resolved within 24 hours with residual mild aphasia. MRI brain revealed multiple foci of cortical infarcts within the left MCA territory with no diffusion/ perfusion mismatch. MRA head showed further pruning of the distal MCA branches within the left sylvian fissure with severe stenosis along the mid‐M1 and minimal flow anteriorly, with contrast enhancement at the site of the stenosis, suggestive of vasculitis. Autoimmune vasculitis panel was unremarkable. Due to suspicion of focal inflammatory vasculopathy related to recent SARS‐CoV‐2 infection, patient was started on intravenous methylprednisolone 1 gram daily for 5 days followed by a prednisone taper. MRA revealed improved blood flow in the left middle cerebral artery and branches. The was discharged on apixaban, aspirin, atorvastatin, and a prednisone taper with mild residual aphasia. Conclusions To our knowledge, this is the first reported case of CNS vasculitis associated with an underlying SARS‐CoV‐2 infection with radiographic improvement of blood flow in the affected vessel within 4 days of treatment with high‐dose steroids. This case supports the use of high‐dose steroids in patients with CNS vasculitis associated with SARS‐CoV‐2 to prevent further stroke burden.

Network connectivity and local transcriptomic vulnerability underpin cortical atrophy progression in Parkinson’s disease

Parkinson’s disease pathology is hypothesized to spread through the brain via axonal connections between regions and is further modulated by local vulnerabilities within those regions. The resulting changes to brain morphology have previously been demonstrated in both prodromal and de novo Parkinson’s disease patients. However, it remains unclear whether the pattern of atrophy progression in Parkinson’s disease over time is similarly explained by network-based spreading and local vulnerability. We address this gap by mapping the trajectory of cortical atrophy rates in a large, multi-centre cohort of Parkinson’s disease patients and relate this atrophy progression pattern to network architecture and gene expression profiles. Across 4-year follow-up visits, increased atrophy rates were observed in posterior, temporal, and superior frontal cortices. We demonstrated that this progression pattern was shaped by network connectivity. Regional atrophy rates were strongly related to atrophy rates across structurally and functionally connected regions. We also found that atrophy progression was associated with specific gene expression profiles. The genes whose spatial distribution in the brain was most related to atrophy rate were those enriched for mitochondrial and metabolic function. Taken together, our findings demonstrate that both global and local brain features influence vulnerability to neurodegeneration in Parkinson’s disease.

Abstract 10514: Compromised Cerebral Artery Integrity is Associated With Brain Tissue Injury and Cognition Deficits in Adolescents With Complex Congenital Heart Disease

Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injury in regions associated with cognitive deficits. Alteration in cerebral artery integrity (CAI), as measured by arterial transit time (ATT), may lead to perfusion deficits, and be a potential cause of brain injury in CCHD. To date, there are no reports of CAI in CCHD or associations between CAI, brain tissue integrity, and cognition in CCHD. Methods: 70 subjects (37 CCHD / 33 controls), 14-18 years of age, undergone surgical palliation (CCHD), and no contraindications for a magnetic resonance imaging (MRI) and healthy controls (age- and sex-matched) participated. Participants completed cognitive testing (Montreal Assessment of Cognition [MoCA] and the Wide Range Assessment of Memory and Learning [General Memory Index, GMI]) and brain MRI using 3.0 Tesla scanner. ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures), and regional brain mean diffusivity [MD] (measure of tissue integrity) were computed in whole brain. Descriptive, partial correlations, and ANCOVA analyses used (covariates, age and sex). Results: Mean MoCA [23.1 ± 4.1 vs. 28.1 ± 2.3; p <.001] and GMI scores [86.8 ± 15.4 vs. 110.3 ± 14.5; p<.001] show significant cognitive deficits in CCHD compared to controls. ATT was significantly increased in CCHD vs controls (mean ± SD, sec, 1.3±0.13 vs 1.22±0.13, p=0.02), respectively, indicating compromised CAI. Partial correlations between ATT, MD values, and cognition (covariates, age and sex, p< 0.005) showed significant associations in various areas including the hippocampus, prefrontal cortices, cerebellum, frontal white matter, anterior and posterior cingulate, frontal cortex, temporal cortices, and midbrain. Conclusion: Adolescents with CCHD have prolonged ATTs compared to controls indicative of compromised CAI and altered cerebral perfusion. CAI is significantly associated with alterations in regional brain tissue integrity and cognitive impairment. Further evaluation is needed to test interventions to increase cerebral perfusion and to protect neural tissue.

Bounded rational decision-making models suggest capacity-limited concurrent motor planning in human posterior parietal and frontal cortex.

While traditional theories of sensorimotor processing have often assumed a serial decision-making pipeline, more recent approaches have suggested that multiple actions may be planned concurrently and vie for execution. Evidence for the latter almost exclusively stems from electrophysiological studies in posterior parietal and premotor cortex of monkeys. Here we study concurrent prospective motor planning in humans by recording functional magnetic resonance imaging (fMRI) during a delayed response task engaging movement sequences towards multiple potential targets. We find that also in human posterior parietal and premotor cortex delay activity modulates both with sequence complexity and the number of potential targets. We tested the hypothesis that this modulation is best explained by concurrent prospective planning as opposed to the mere maintenance of potential targets in memory. We devise a bounded rationality model with information constraints that optimally assigns information resources for planning and memory for this task and determine predicted information profiles according to the two hypotheses. When regressing delay activity on these model predictions, we find that the concurrent prospective planning strategy provides a significantly better explanation of the fMRI-signal modulations. Moreover, we find that concurrent prospective planning is more costly and thus limited for most subjects, as expressed by the best fitting information capacities. We conclude that bounded rational decision-making models allow relating both behavior and neural representations to utilitarian task descriptions based on bounded optimal information-processing assumptions.

ADHD Children Identification With Multiview Feature Fusion of fNIRS Signals

Attention-deficit/hyperactivity disorder (ADHD) is one of highly prevalent neurodevelopmental disorders in children. It is of great value to find an objective, simple and non-invasive diagnosis method to compliment current diagnostic criteria. A discriminant correlation analysis (DCA) based multi-view feature fusion method combined with support vector machine (SVM) was proposed to identify ADHD children. The functional near-infrared spectroscopy signals from twenty-five ADHD children and twenty-five typically developing children were recorded during an n-back task. The DCA method was used to find a joint feature by fusing the features extracted in 1-back condition and 0-back condition. Then a SVM model was trained with the joint feature to identify the ADHD children. The results showed that the DCA-SVM method could identify the ADHD children with a classification accuracy of 88.0%. Meanwhile, part of left dorsolateral prefrontal cortex and left medial prefrontal cortex, posterior superior frontal cortex and bilateral temporal cortex were more discriminative in 1-back condition, left dorsolateral prefrontal cortex and part of left medial prefrontal cortex were more discriminative in 0-back condition. Our findings indicated that the DCA-SVM method is promising in clinical diagnosis of ADHD children.

Longitudinal effects of antidepressant treatment on resting state functional connectivity in adolescents with major depressive disorder

IntroductionAdolescents with major depressive disorder (MDD) often show reduced prefrontal functional connectivity with the subcortical regions than healthy controls (HC) (Tang et al., 2018). However, relatively little is known about longitudinal effects of antidepressant (AD) treatment on resting state functional connectivity (RSFC) in the prefrontal cortex (PFC).ObjectivesThis study aimed to investigate abnormal PFC RSFC in MDD adolescents compared to HC and longitudinal effects of AD on PFC RSFC.Methods This study included 59 adolescents with MDD and 43 HC. MDD adolescents were treated with escitalopram in an 8 week, open-label trial. The treatment outcome was assessed by Children’s Depression Rating Scale (CDRS-R) and patients showing at least a 40% improvement in CDRS-R scores from baseline to week 8 were defined as “responders”. Functional and T1 images collected before and after treatment were processed using AFNI and Freesurfer. Our seed was the lateral PFC (LPFC, BA46). T-tests and repeated measures ANCOVAs, controlling for age and IQ, were conducted to examine abnormal PFC RSFC and longitudinal effects of AD on LPFC RSFC.ResultsRelative to HC, MDD showed increased LPFC RSFC with the posterior middle temporal gyrus (pMTG) and superior frontal cortex (SFG) involved in attentional networks. Responders showed greater changes in LPFC RSFC with the MTG and SFG after AD treatment compared to non-responders and HC (Figure 1).ConclusionsOur finding suggests that reduced LPFC RSFC with the pMTG and SFG reflecting decreased attentional network connectivity may serve as a biomarker to predict AD treatment outcome in adolescents with MDD.DisclosureNo significant relationships.