Bilateral Anterior Cingulate Research Articles

Characteristics of subjective olfactory dysfunction and imaging features in patients with traumatic olfactory disorders: a retrospective case-control study.

Olfactory dysfunction caused by head trauma poses significant challenges in clinical diagnosis and treatment. The primary difficulty arises from direct injuries to olfactory-related brain tissues. Although imaging provides the most direct method to evaluate such injuries, there is no standardized international diagnostic criterion for olfactory dysfunction based on imaging. We designed this study to compare the subjective olfactory function differences and brain gray-matter (GM) and white-matter (WM) volume differences between patients with traumatic olfactory dysfunction and those with other types of olfactory dysfunction and to determine the characteristics of subjective olfactory dysfunction and imaging features in patients with traumatic olfactory disorders. The findings of this study can provide a theoretical basis for the diagnosis of traumatic olfactory disorders. This ethics committee-approved, retrospective case-control study included 56 patients with traumatic olfactory dysfunction (trauma group) and 45 patients with other types of olfactory dysfunction (e.g., postinfection, nasal inflammation, idiopathic disease). The "Sniffin' Sticks" olfactory function test was used to analyze the subjective olfactory function differences between the two groups, and voxel-based morphometry (VBM) was used to compare the GM volume (GMV) and WM volume (WMV) of brain regions between the two groups. (I) There was no statistical difference in age distribution between the trauma group (41.55±11.77 years) and the control group (38.87±14.37 years; P>0.05). (II) The trauma group had significantly lower total scores and subtest scores on the Sniffin' Sticks olfactory test compared to the control group [odor threshold test (OT): 1.04±0.33 vs. 1.67±1.42; odor discrimination test (OD): 2.93±2.25 vs. 5.42±3.66; odor identification test (OI): 2.77±1.94 vs. 6.71±3.55; total scores: 6.74±3.91 vs. 13.81±7.63; all P values <0.05]. (III) Compared with the control group, the trauma group had significantly reduced GMV and WMV in the bilateral orbitofrontal cortex, bilateral anterior cingulate gyrus, bilateral cingulate gyrus, bilateral rectus gyrus, bilateral olfactory cortex, right superior frontal gyrus, bilateral insula, bilateral caudate nucleus, and bilateral thalamus [Pfamily-wise error (FWE)<0.05]. (IV) There was a significant positive correlation between the odor identification function scores and GMV in certain brain regions (PFWE<0.05), and the GMV in these regions was reduced in the trauma group compared to the control group. Compared to patients with other types of olfactory dysfunction, patients with traumatic olfactory dysfunction have poorer subjective olfactory functions and more severe damage to olfactory-related brain regions, including the bilateral orbitofrontal cortex, anterior cingulate gyrus, cingulate gyrus, rectus gyrus, insula, and olfactory cortex. The olfactory nerve damage in these brain regions can be used as a basis for the diagnosis of traumatic olfactory disorders.

Altered Neural Processing of Interoception in Patients With Functional Neurological Disorder: A Task-Based fMRI Study.

Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.

Application of proton magnetic resonance spectroscopy in metabolic alterations of prefrontal white and gray matter in depression adolescents

BACKGROUND Cases of depression among adolescents are gradually increasing. The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention. Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus, frontal lobe white matter, and the thalamus. AIM To explore the application of proton magnetic resonance spectroscopy (1H-MRS) in the metabolic alterations in the prefrontal white matter (PWM) and gray matter (GM) in adolescents with depression. METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate (NAA), choline (Cho) complexes, creatine (Cr), and myo-inositol (mI) in bilateral PWM, anterior cingulate GM, and thalami of 31 adolescent patients with depression (research group) and 35 healthy adolescents (control group), and the NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. Meanwhile, Hamilton Depression Scale (HAMD) and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents. The correlation of brain metabolite levels with scale scores was also analyzed. RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient (MQ) compared with the control group (P &lt; 0.05). Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents (P &lt; 0.05). The mI/Cr ratios were found to be similar in both groups (P &gt; 0.05). The bilateral anterior cingulate GM NAA/Cr, Cho/Cr, and mI/Cr also did not demonstrate marked differences (P &gt; 0.05). No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami (P &gt; 0.05), while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents (P &lt; 0.05). A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr (P &lt; 0.05). In adolescents with depressions, MQ positively correlated with right PWH NAA/Cr, left PWH Cho/Cr, and bilateral thalamic Cho/Cr and mI/Cr. CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression, and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment. There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.

Structural and functional correlates of olfactory reward processing in behavioral variant frontotemporal dementia

The behavioral variant of frontotemporal dementia (bvFTD) includes symptoms that reflect altered pursuit of rewards, including food, alcohol, and money. Little is known, however, about how these reward changes relate to atrophy and functional connectivity within reward-related regions. The goal of this study was to examine the structural and functional correlates of valence perception for olfactory rewards in 24 patients with bvFTD. Regression analysis of resting-state brain functional connectivity indicated that more positive valence ratings of olfactory stimuli were predicted by ventral pallidum connectivity to other reward circuit regions, particularly functional connectivity between ventral pallidum and bilateral anterior cingulate cortex/ventromedial prefrontal cortex. Structural analysis showed that atrophy of the anterior cingulate cortex was also significantly associated with perceiving stimuli as more rewarding. Finally, there was a significant interaction between ventral pallidum connectivity and atrophy of the anterior cingulate cortex. More specifically, the ventral pallidum connectivity had a greater effect on the positive perception of olfactory stimuli in the setting of low anterior cingulate cortex volume. These findings indicate that atrophy and functional connectivity within reward-relevant regions exert independent and interacting effects on the perception of pleasantness in bvFTD, potentially due to changes in hedonic “liking” signals.

Exploring the Utility of a Functional Magnetic Resonance Imaging Cannabis Cue-Reactivity Paradigm in Treatment-Seeking Adults With Cannabis Use Disorder

BackgroundFunctional magnetic resonance imaging studies examining cue reactivity in cannabis use disorder (CUD) either have had small sample sizes or have involved non–treatment-seeking participants. As a secondary analysis, we administered a functional magnetic resonance imaging cue-reactivity task to participants with CUD enrolled in 2 separate clinical trials (varenicline or repetitive transcranial magnetic stimulation) to determine the task activation patterns for treatment-seeking participants with CUD. We aimed to determine the activation patterns for the total sample and behavioral correlates. We additionally compared studies to determine if patterns were consistent. MethodsTreatment-seeking participants with moderate or severe CUD had behavioral craving measured at baseline using the Marijuana Craving Questionnaire–Short Form and completed a visual cannabis cue-reactivity task during functional magnetic resonance imaging (measuring the blood oxygen level–dependent response) following 24 hours of cannabis abstinence. ResultsThe sample included 65 participants (n = 37: varenicline trial; n = 28: repetitive transcranial magnetic stimulation trial; 32% female; mean age = 30.4 ± 9.9 years). When comparing cannabis images versus matched neutral images, participants showed greater blood oxygen level–dependent response in bilateral ventromedial-prefrontal, dorsolateral-prefrontal, anterior cingulate, and visual cortices as well as the striatum. There was stronger task-based functional connectivity between the medial prefrontal cortex and both the amygdala and the visual cortex. Craving negatively correlated with blood oxygen level–dependent response in the left ventral striatum (R2 = −0.32; p = .01) in the full sample. There were no significant differences in either activation or task-based functional connectivity between studies. ConclusionsIn 2 separate treatment-seeking groups with CUD, there was increased cannabis cue reactivity and task-based functional connectivity in regions related to executive function and reward processing. Cannabis craving was negatively associated with cue reactivity in the left ventral striatum.

P40: Memantine effects on resting-state EEG sources in Alzheimer’s disease

Objectives: Several studies have shown that acetylcholinesterase inhibitors (AChEIs) decrease delta or theta activity, increase alpha activity on Electroencephalography (EEG) in Alzheimer’s disease (AD) patients. The effects of memantine on EEG in AD patients are not as well understood as those of AChEIs. The present study investigated the electrocortical effects of 3 months memantine medication in AD patients.Methods: EEG was recorded in 28 patients with AD (mean age 83.3 ± 4.6 years, 19 females) before and 3 months after the onset of memantine medication. Source localization was applied to the EEG using exact low-resolution brain electromagnetic tomography (eLORETA) in 8 frequency bands (delta, theta, alpha-1, alpha-2, beta-1, beta- 2, beta-3, gamma). Differences in source strengths from before to after memantine treatment were compared per frequency band using t-statistics (corrected for multiple testing over frequency bands and voxels).Results: Theta activity significantly decreased in bilateral anterior cingulate gyrus, bilateral posterior cingulate gyrus, right parahippocampal gyrus, right insula, right fusiform gyrus, bilateral precuneus, right uncus and right temporal gyrus. Alpha-1 and alpha-2 activity decreased in the anterior cingulate gyrus. Beta-1 activity significantly decreased in the anterior and posterior cingulate gyrus. There were no areas of increased EEG activity in any frequency bands.Conclusions: We found that memantine reduced theta activity similarly to AChEIs. This finding may be related to the cognitive improvements of memantine. Whereas the decrease of beta-1, alpha-1 and alpha-2 activity in the anterior cingulate gyrus was different from AChEIs. Further studies are required to elucidate these differences.

The abnormalities of brain function in females with primary insomnia: a resting-state functional magnetic resonance imaging study.

The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC). A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function. ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L. Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability.

Bulimia nervosa selectively reshapes the structure and intrinsic function of anterior insula subregions associated with cognition-emotion integration

BackgroundExisting evidence suggests that anterior insula plays a crucial role in cognitive control and emotional regulation and is implicated in the onset and maintenance of bulimia nervosa (BN). However, it remains unclear how structural and functional abnormalities in specific subregions of anterior insula contribute to BN. MethodsIn this study, we analyzed structural MRI and resting-state functional MRI data from 54 BN patients and 56 healthy controls (HCs). We conducted voxel-based morphometry, amplitude of low frequency fluctuation (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz) and seed-based whole-brain functional connectivity (FC) analysis of the anterior insula subregions for both groups. Additionally, we investigated the correlation between neuroimaging findings and clinical characteristics in the BN group. ResultsOur findings revealed that BN patients exhibited reduced gray matter volume in the right dorsal anterior insula (dAI) and bilateral ventral anterior insula (vAI) and demonstrated decreased ALFF in slow-5 band of bilateral dAI. The BN group also showed increased FC between bilateral dAI and precuneus or right superior frontal gyri which significantly correlated with the severity of BN or its key symptom. In addition, the decreased FC between bilateral vAI and anterior cingulate and paracingulate gyri and/or median cingulate and paracingulate gyri were both significantly correlated with the severity and its restrained eating behavior. ConclusionsOur findings further indicate that the functional separation of anterior insula subregions may underlie the pathophysiology of BN. Notably, the vAI associated with emotional processing may serve as a promising neuroimaging biomarker which could inform therapeutic strategy.

Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas

ObjectiveThis study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. MethodsNinety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. ResultsThe seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. ConclusionsOur study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder

BackgroundThis meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD).MethodsA whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software.ResultsA total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences.ConclusionsThe present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Culture, prefrontal volume, and memory.

Prior cross-cultural studies have demonstrated differences among Eastern and Western cultures in memory and cognition along with variation in neuroanatomy and functional engagement. We further probed cultural neuroanatomical variability in terms of its relationship with memory performance. Specifically, we investigated how memory performance related to gray matter volume in several prefrontal lobe structures, including across cultures. For 58 American and 57 Taiwanese young adults, memory performance was measured with the California Verbal Learning Test (CVLT) using performance on learning trial 1, on which Americans had higher scores than the Taiwanese, and the long delayed free recall task, on which groups performed similarly. MRI data were reconstructed using FreeSurfer. Across both cultures, we observed that larger volumes of the bilateral rostral anterior cingulate were associated with lower scores on both CVLT tasks. In terms of effects of culture, the relationship between learning trial 1 scores and gray matter volumes in the right superior frontal gyrus had a trend for a positive relationship in Taiwanese but not in Americans. In addition to the a priori analysis of select frontal volumes, an exploratory whole-brain analysis compared volumes-without considering CVLT performance-across the two cultural groups in order to assess convergence with prior research. Several cultural differences were found, such that Americans had larger volumes in the bilateral superior frontal and lateral occipital cortex, whereas Taiwanese had larger volumes in the bilateral rostral middle frontal and inferior temporal cortex, and the right precuneus.

Gray matter volume associations in youth with ADHD features of inattention and hyperactivity/impulsivity.

Prior research has shown smaller cortical and subcortical gray matter volumes among individuals with attention-deficit/hyperactivity disorder (ADHD). However, neuroimaging studies often do not differentiate between inattention and hyperactivity/impulsivity, which are distinct core features of ADHD. The present study uses an approach to disentangle overlapping variance to examine the neurostructural heterogeneity of inattention and hyperactivity/impulsivity dimensions. We analyzed data from 10,692 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study. Confirmatory factor analysis was used to derive factors representing inattentive and hyperactive/impulsive traits. We employed structural equation modeling to examine these factors' associations with gray matter volume while controlling for the shared variance between factors. Greater endorsement of inattentive traits was associated with smaller bilateral caudal anterior cingulate and left parahippocampal volumes. Greater endorsement of hyperactivity/impulsivity traits was associated with smaller bilateral caudate and left parahippocampal volumes. The results were similar when accounting for socioeconomic status, medication, and in-scanner motion. The magnitude of these findings increased when accounting for overall volume and intracranial volume, supporting a focal effect in our results. Inattentive and hyperactivity/impulsivity traits show common volume deficits in regions associated with visuospatial processing and memory while at the same time showing dissociable differences, with inattention showing differences in areas associated with attention and emotion regulation and hyperactivity/impulsivity associated with volume differences in motor activity regions. Uncovering such biological underpinnings within the broader disorder of ADHD allows us to refine our understanding of ADHD presentations.

Functional and structural abnormalities of the speech disorders: a multimodal activation likelihood estimation meta-analysis.

Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the common abnormalities shown by all disorders, remain unclear. Herein, a meta-analysis was conducted to integrate the results of 70 studies that compared 1843 speech disorder patients (dysarthria, dysphonia, stuttering, and aphasia) to 1950 healthy controls in terms of brain activity, functional connectivity, gray matter, and white matter fractional anisotropy. The analysis revealed that compared to controls, the dysarthria group showed higher activity in the left superior temporal gyrus and lower activity in the left postcentral gyrus. The dysphonia group had higher activity in the right precentral and postcentral gyrus. The stuttering group had higher activity in the right inferior frontal gyrus and lower activity in the left inferior frontal gyrus. The aphasia group showed lower activity in the bilateral anterior cingulate gyrus and left superior frontal gyrus. Across the four disorders, there were concurrent lower activity, gray matter, and fractional anisotropy in motor and auditory cortices, and stronger connectivity between the default mode network and frontoparietal network. These findings enhance our understanding of the neural basis of speech disorders, potentially aiding clinical diagnosis and intervention.

Ventral Anterior Cingulate Atrophy as a Predisposing Factor for Transient Global Amnesia.

This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain

To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. Prospective case series. 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.

21 Patterns of Neural Activation Associated with Judgments of Learning and Retrospective Confidence Judgments in Individuals with TBI

Objective:Metacognition is defined as the ability to observe, monitor, and make judgments about one’s own cognitive status. Judgments of learning (JOLs) and retrospective confidence judgments (RCJs) are two elements of metacognition related to memory, or metamemory. JOLs refer to one’s assumptions of their memory performance prior to completing a memory task, while RCJs describe one’s subjective assessment of their memory performance after they have completed the task. Traumatic brain injury (TBI) is known to negatively impact general metacognitive functioning. However, the nuanced effects of TBI on constituent metacognitive subprocesses like JOLs and RCJs remain unclear. This study aimed to characterize patterns of brain activity that occur when individuals with TBI render JOLs and RCJs during a meta-memory task. Differences between JOL- and RCJ-related patterns of activation were also explored.Participants and Methods:20 participants with moderate-to-severe TBI completed a metacognition task while undergoing functional magnetic resonance imaging (fMRI). Participants were first exposed to target slides with a set of polygons placed in specific locations, then asked to identify the target slides within a set of distractors. Before identifying the target slides, participants rated how well they believed they would remember the polygons’ shape and location (JOL). After answering, they rated how confident they were that the answer they provided was correct (RCJ). First-level time series analyses of fMRI data were conducted for each participant using FSL FEAT. Higher-level random effects modeling was then performed to assess average activation across all participants. Finally, contrasts were applied to examine and compare JOL- and RCJ-specific patterns of activation.Results:JOLs were associated with activation of the left frontal gyri, bilateral anterior cingulate, left insula, and right putamen (p &lt; 0.01). RCJs were associated with activation of the bilateral frontal gyri, bilateral posterior and anterior cingulate, left insula, right putamen, and left thalamus (p &lt; 0.01). Compared to RCJs, JOLs demonstrated greater left insula activation (p &lt; 0.01). Compared to JOLs, RCJs demonstrated greater activation of the left superior frontal gyrus, bilateral middle frontal gyrus, and bilateral anterior cingulate (p &lt; 0.01).Conclusions:The areas of activation found in this study were consistent with structures previously identified in the broader metacognition literature. Overall, RCJs produced activity in a greater number of regions that was more bilaterally distributed compared to JOLs. Moreover, several regions that were active during both metacognitive subprocesses tended to be even more active during RCJs. A hypothesis for this observation suggests that, unlike JOLs, the additional involvement of reflecting on one’s immediate memory of completing the task during RCJs may require greater recruitment of resources compared to JOLs. Importantly, these findings suggest that, while different metacognitive subprocesses may recruit similar brain circuitry, some subprocesses may require more potent and widespread activation of this circuitry than others. As such, subprocesses with greater activational needs and complexity, such as RCJs, may be more susceptible to damage caused by TBI. Future research should aim to compare patterns of activation associated with certain metacognitive subprocesses between survivors of TBI and healthy controls.

Disrupted Gray Matter Networks Associated with Cognitive Dysfunction in Cerebral Small Vessel Disease.

This study aims to investigate the disrupted topological organization of gray matter (GM) structural networks in cerebral small vessel disease (CSVD) patients with cerebral microbleeds (CMBs). Subject-wise structural networks were constructed from GM volumetric features of 49 CSVD patients with CMBs (CSVD-c), 121 CSVD patients without CMBs (CSVD-n), and 74 healthy controls. The study used graph theory to analyze the global and regional properties of the network and their correlation with cognitive performance. We found that both the control and CSVD groups exhibited efficient small-world organization in GM networks. However, compared to controls, CSVD-c and CSVD-n patients exhibited increased global and local efficiency (Eglob/Eloc) and decreased shortest path lengths (Lp), indicating increased global integration and local specialization in structural networks. Although there was no significant global topology change, partially reorganized hub distributions were found between CSVD-c and CSVD-n patients. Importantly, regional topology in nonhub regions was significantly altered between CSVD-c and CSVD-n patients, including the bilateral anterior cingulate gyrus, left superior parietal gyrus, dorsolateral superior frontal gyrus, and right MTG, which are involved in the default mode network (DMN) and sensorimotor functional modules. Intriguingly, the global metrics (Eglob, Eloc, and Lp) were significantly correlated with MoCA, AVLT, and SCWT scores in the control group but not in the CSVD-c and CSVD-n groups. In contrast, the global metrics were significantly correlated with the SDMT score in the CSVD-s and CSVD-n groups but not in the control group. Patients with CSVD show a disrupted balance between local specialization and global integration in their GM structural networks. The altered regional topology between CSVD-c and CSVD-n patients may be due to different etiological contributions, which may offer a novel understanding of the neurobiological processes involved in CSVD with CMBs.

Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens

To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens, we used probabilistic diffusion tractography and graph theory to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. In conclusion, the decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity of CSVD.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.

Evidence Accumulation and Neural Correlates of Uncertainty in Obsessive-Compulsive Disorder

BackgroundDecision making is frequently associated with risk taking under uncertainty. Elevated intolerance of uncertainty is suggested to be a critical feature of obsessive-compulsive disorder (OCD). However, impairments of latent constructs of uncertainty processing and its neural correlates remain unclear in OCD. MethodsIn 83 participants (24 OCD patients treated with capsulotomy, 28 OCD control participants, and 31 healthy control participants), we performed magnetic resonance imaging using a card gambling task in which participants made decisions whether to bet or not that the next card would be larger than the current one. A hierarchical drift diffusion model was used to dissociate speed and amount of evidence accumulated before a decisional threshold (i.e., betting or no betting) was reached. ResultsHigh uncertainty was characterized by a smaller amount of evidence accumulation (lower thresholds), thus dissociating uncertainty from conflict tasks and highlighting the specificity of this task to test value-based uncertainty. OCD patients exhibited greater caution with poor performance and greater evidence accumulation overall along with slower speed of accumulation, particularly under low uncertainty. Bilateral dorsal anterior cingulate and anterior insula distinguished high- and low-uncertainty decision processes in healthy control participants but not in the OCD groups, indicating impairments in anticipation of differences in outcome variance and salience network activity. There were no behavioral or imaging differences relating to capsulotomy despite improvements in OCD symptoms. ConclusionsOur findings highlight greater impairments particularly in more certain trials in the OCD groups along with impaired neural differentiation of high and low uncertainty and suggest uncertainty processing as a trait cognitive endophenotype rather than a state-specific factor.