Orbitofrontal Research Articles

Representations of the intrinsic value of information in mouse orbitofrontal cortex.

Animals are motivated to seek information that does not influence reward outcomes, suggesting that information has intrinsic value. We have developed an odor-based information seeking task that reveals that mice choose to receive information even though it does not alter the reward outcome. Moreover, mice are willing to pay for information by sacrificing water reward, suggesting that information is of intrinsic value to a mouse. We used a microendoscope to reveal neural activity in orbitofrontal cortex (OFC) while mice learned the information seeking task. We observed the emergence of distinct populations of neurons responsive to odors predictive of information and odors predictive of water reward. A latent variable model recapitulated these different representations in the low-dimensional dynamics of OFC neuronal population activity. These data suggest that mice have evolved separate pathways to represent the intrinsic value of information and the extrinsic value of water reward. Thus, the desire to acquire knowledge is observed in mice, and the value of this information is represented in the OFC. The mouse now provides a facile experimental system to study the representation of the value of information, a higher cognitive variable.

Early childhood family threat and longitudinal amygdala-mPFC circuit development: Examining cortical thickness and gray matter-white matter contrast

Early threat-associated cortical thinning may be interpreted as accelerated cortical development. However, non-adaptive processes may show similar macrostructural changes. Examining cortical thickness (CT) together with grey/white-matter contrast (GWC), a proxy for intracortical myelination, may enhance the interpretation of CT findings. In this prospective study, we examined associations between early life family-related threat (harsh parenting, family conflict, and neighborhood safety) and CT and GWC development from late childhood to middle adolescence. MRI was acquired from 4200 children (2069 boys) from the Generation R study at ages 8, 10 and 14 years (in total 6114 scans), of whom 1697 children had >1 scans. Linear mixed effect models were used to examine family factor-by-age interactions on amygdala volume, caudal and rostral anterior cingulate (ACC) and medial orbitofrontal cortex (mOFC) CT and GWC. A neighborhood safety-by-age-interaction was found for rostral ACC GWC, suggesting less developmental change in children from unsafe neighborhoods. Moreover, after more stringent correction for motion, family conflict was associated with greater developmental change in CT but less developmental change in GWC. Results suggest that early threat may blunt ACC GWC development. Our results, therefore, do not provide evidence for accelerated threat-associated structural development of the amygdala-mPFC circuit between ages 8–14 years.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere. The activations in the face and object processing ventrolateral visual cortical stream regions FFC, PIT, V8 and TE2p were higher in the object-location in scene task than the reward-location task, and were higher in the right hemisphere. For reward-location in scene episodic memory, activations were also high in the ventromedial visual cortical spatial stream to the hippocampus, but were also selectively high in storage in key reward cortical regions (ventromedial prefrontal 10r, 10v, 10d; pregenual anterior cingulate d32, p24, p32, s32; and medial orbitofrontal cortex reward-related pOFC, 11l, OFC). For word-pair episodic memory, activations were lower in the ventromedial visual and medial parahippocampal spatial cortical stream, and were higher in language-related regions in Broca's area (44, 45, 47l), and were higher in the left hemisphere for these regions and for the many highly connected inferior frontal gyrus regions in the left hemisphere. Further, effective connectivity analyses during the episodic memory tasks showed that the direction of connectivity for these systems was from early visual cortical regions V2-V4 to the ventromedial visual cortical regions VMV1-3 and VVC for spatial scene processing; was from the pregenual anterior cingulate and orbitofrontal cortex reward systems to the hippocampal system; and was from the FFC/V8/PIT system to TE2p in the visual inferior temporal visual cortex, which has connectivity to lateral parahippocampal TF, which in turn has forward effective connectivity to the hippocampus.

Semantic inhibition impairment in college students with depressive states as evidenced by EEG and pupillometry during the hayling task

In this study we tested whether depression is associated with impaired semantic inhibition, resulting in symptoms of rumination and anhedonia. For this purpose and using the Beck Depression Inventory II (BDI-II) college students with depressive states (DEP) and matched controls (CTL) performed a Hayling’s task, while EEG and pupillometry measures were recorded. Participants were asked to complete sentential contexts with either a highly associated word (initiation) or a non-related word (inhibition), in response to randomly presented trial-by-trial cues. The DEP group, compared to the CTL group, showed lower performance, and reduced frontal negativity (N450) in inhibition trials. Source analyses revealed greater activation for inhibition trials than for initiation trials in bilateral orbitofrontal cortex for the CTL group, but the difference was reduced and more left lateralized for the DEP group. In addition, the DEP group showed more pupil size reactivity to inhibition trials than the CTL group, indicating higher cognitive effort during semantic inhibition. Finally, self-reported rumination and anhedonia correlated with N450 in inhibition trials, and rumination correlated with pupil dilation. Overall, this research contributes to understanding the neural underpinnings of impaired semantic inhibition in individuals with depression, with potential clinical applications.

Distinct functional connectivity phenotypes in preadolescent children with binge eating disorder by BMI status.

The neurobiological mechanisms underpinning binge eating disorder (BED) in children remain largely unclear, as the alterations that have been identified to date may be attributable to BED, obesity, or compound effects. This study aimed to delineate functional connectivity (FC) patterns in inhibitory control and reward networks in preadolescent children with and without BED from the Adolescent Brain Cognitive Development (ABCD) Study according to BMI. Resting-state FC was examined in the inhibitory control network by using seeds in the dorsolateral prefrontal cortex, the anterior cingulate cortex, and the posterior cingulate cortex, whereas the reward network included seeds in the orbitofrontal cortex, nucleus accumbens, and amygdala. Seed-to-voxel analyses characterized FC differences between preadolescent children with BED with a high BMI and those with BED with a low BMI. We identified that BED was characterized by reduced connectivity between the reward network and regions in the default mode network, irrespective of weight status. Participants with BED also presented with hypoconnectivity in fronto-amygdalar circuits, which has been consistently associated with impaired emotion regulation capacity. Our findings support that FC alterations between the reward network and the default mode network may be specifically impacted by the presence of BED as opposed to weight status.

Monorhinal and Birhinal Odor Processing in Humans: an fMRI investigation.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. However, the lateralization of olfactory processes is known to depend on the task and nature of stimuli. It still remains unclear whether olfactory system projections in humans also correspond to functional pathways during olfactory tasks without any trigeminal, perceptual or cognitive-motor components. Twenty young healthy subjects with a normal sense of smell took part in an olfactory functional magnetic resonance imaging (fMRI) study. We used two types of nostril specific stimulation, passive (no sniffing) and active (with sniffing), with phenyl ethyl alcohol, a pure olfactory stimulant, to investigate fMRI activity patterns in primary and secondary olfactory-related brain structures. Irrespective of the stimulated nostril and the type of stimulation, we detected symmetrical activity in primary and secondary olfactory-related brain structures such as the primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. In the absence of perceptual or cognitive-motor task demands, the perception of monorhinally presented pure odors is processed bilaterally in the brain.

Abnormal changes in neuropsychological function, brain structure and cerebral perfusion in patients with unruptured intracranial aneurysms.

Patients with unruptured intracranial aneurysms (UIAs) often experience emotional changes and cognitive impairments. However, the specific mechanisms underlying these impairments are still not fully understood. In the present study, voxel-based morphometry (VBM) and surface-based morphometry (SBM) were employed to investigate structural alterations in 49 patients diagnosed with UIAs compared with 50 healthy controls. Additionally, this study aimed to analyze the correlations among cortical morphological indices, cerebral blood perfusion values and neuropsychological test results. Compared with control group, UIA patients exhibited increased gray matter volume in the right anterior orbitofrontal cortex and decreased gray matter volume in the left thalamus pulvinar and hippocampus. Furthermore, the fractal dimension was lower in the right postcentral gyrus and entorhinal cortex. The cerebral perfusion values in the abnormal brain regions demonstrated a downward trend, which was associated with a reduction in gray matter volume in the left thalamus pulvinar and hippocampus, elevated anxiety levels and impaired executive function. UIA patients are prone to cognitive impairment and emotional dysregulation, which are accompanied by subtle changes in local gray matter volume and decreases in fractal dimension and cerebral blood flow. These findings provide new insights into the potential mechanisms underlying the cognitive impairment observed in UIA patients.

Shared and distinct alterations in brain morphology in children with ADHD and obesity: Reduced cortical surface area in ADHD and thickness in overweight/obesity

ObjectiveTo investigate shared versus distinct differences in brain structure among children with ADHD and obesity, we examined the morphology of regions implicated in cognitive control and reward function in a single cross-sectional cohort of children with and without ADHD and overweight/obesity (OV/OB). MethodParticipants included 471 children ages 8–12 years with ADHD (n = 244; 58 OV/OB) and neurotypical (NT) controls (n = 227; 81 OV/OB) classified as healthy-weight (HW; BMI %ile 5th to <85th) vs. having OV/OB (BMI %ile≥85th). Structural MRI was performed to obtain measures of cortical and subcortical morphology and compared across ADHD × BMI groups. ResultsSurface area was generally lower in ADHD vs. NT including in anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), medial (m)PFC, and primary motor (M1) cortex. In contrast, cortical thickness was generally lower in OV/OB vs. HW for ACC, dlPFC, orbitofrontal cortex (OFC), mPFC, and supplementary motor cortex (SMC). Furthermore, ADHD × OV/OB interactions were observed for the ACC and OFC, with the lowest ACC volume in the ADHD + OV/OB group and the highest OFC surface area in the NT + OV/OB group. Subcortical volumes did not differ between groups. ConclusionsOur findings reveal distinct alterations in cortical morphology in association with ADHD and overweight, with cortical surface area reduced in ADHD vs. thickness reduced in OV/OB. Additionally, the findings provide evidence of combined effects of ADHD × OV/OB in brain regions integral to cognition and motivation. Our results support further investigation of causes and correlates of shared and distinct ADHD- and OV/OB-associated differences in developing frontocingulate morphology.

Association of Exercise with Better Olfactory Performance and Higher Functional Connectivity Between the Olfactory Cortex and the Prefrontal Cortex: A Resting-State Functional Near-Infrared Spectroscopy Study.

Background: Olfactory deterioration is suggested to be a predictor of some neurodegenerative diseases. Recent studies indicate that physical exercise has a positive relationship with olfactory performance, and a subregion in the prefrontal cortex (PFC) may play an important role in olfactory processing. The PFC is not only related to olfactory function but it also engages in complex functions such as cognition and emotional processing. Methodology: Our study compared the functional connectivity between the olfactory cortex and the PFC in healthy individuals who exercised regularly and healthy persons who did not. Those who exercised more than three times/week for at least 30 min each time were considered the exercise group, and those who did not meet this exercise criteria were considered the nonexercise group. We also assessed their odor threshold. Participants were aged 55 years or older, and the two groups were balanced for age, sex, body mass index, and educational level. Results: We found that compared with individuals who did not exercise, exercisers had a significantly lower threshold for detecting odors. In addition, the olfactory cortex had stronger connectivity with the PFC in exercisers than in nonexercisers. More specifically, when the PFC was grouped into three subregions, namely, the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and frontopolar cortex (FPA), Pearson correlation analysis revealed stronger connectivity between the VLPFC and the orbitofrontal cortex (OFC), between the OFC and the FPA, and between the left and right OFC hemispheres in the exercisers. In addition, Granger causality indicated higher directional connectivity from the DLPFC to the OFC in exercisers than in nonexercisers. Conclusion: Our findings indicated that the exercise group not only had better olfactory performance but also had stronger functional connectivity between the olfactory cortex and the PFC than nonexercise group.

Alterations in orbitofrontal cortex communication relate to suicidal attempts in patients with major depressive disorder

BackgroundInvestigating how the interaction between the orbitofrontal cortex (OFC) and various brain regions/functional networks in major depressive disorder (MDD) patients with a history of suicide attempt (SA) holds importance for understanding the neurobiology of this population. MethodsWe employed resting-state functional magnetic resonance imaging (rs-fMRI) to analyze the OFC's functional segregation in 586 healthy individuals. A network analysis framework was then applied to rs-fMRI data from 86 MDD-SA patients and 85 MDD-Control patients, utilizing seed mappings of OFC subregions and a multi-connectivity-indicator strategy involving cross-correlation, total interdependencies, Granger causality, and machine learning. ResultsFour functional subregions of left and right OFC, were designated as seed regions of interest. Relative to the MDD-Control group, the MDD-SA group exhibited enhanced functional connectivity (FC) and attenuated interaction between the OFC and the sensorimotor network, imbalanced communication between the OFC and the default mode network, enhanced FC and interaction between the OFC and the ventral attention network, enhanced interaction between the OFC and the salience network, and attenuated FC between the OFC and the frontoparietal network. LimitationsThe medication and treatment condition of patients with MDD was not controlled, so the medication effect on the alteration model cannot be affirmed. ConclusionThe findings suggest an imbalanced interaction pattern between the OFC subregions and a set of cognition- and emotion-related functional networks/regions in the MDD-SA group.

Orbitofrontal cortex to dorsal striatum circuit is critical for incubation of oxycodone craving after forced abstinence.

Relapse is a major challenge in treating opioid addiction, including oxycodone. During abstinence, oxycodone seeking progressively increases, a phenomenon termed incubation of oxycodone craving. We previously demonstrated a causal role of orbitofrontal cortex (OFC) in this incubation. Here, we studied the interaction between glutamatergic projections from OFC and dopamine 1-family receptor (D1R) signaling in dorsal striatum (DS) in this incubation in male rats. We first examined the causal role of D1R signalling in DS in incubated oxycodone seeking. Next, we combined fluorescence-conjugated cholera toxin subunit B (CTb-555, a retrograde tracer) with Fos (a neuronal activity marker) to assess whether the activation of OFC→DS projections was associated with incubated oxycodone seeking. We then used a pharmacological asymmetrical disconnection procedure to examine the role of the interaction between projections from OFC and D1R signalling in DS in incubated oxycodone seeking. We also tested the effect of unilateral pharmacological inactivation of OFC or unilateral D1R blockade of DS on incubated oxycodone seeking. Finally, we assessed whether contralateral disconnection of OFC→DS projections impacted non-incubated oxycodone seeking on abstinence day 1. We found that D1R blockade in DS decreased incubated oxycodone seeking and OFC→DS projections were activated during incubated oxycodone seeking. Moreover, anatomical disconnection of OFC→DS projections, but not unilateral inactivation of OFC or unilateral D1R blockade in DS, decreased incubated oxycodone seeking. Lastly, contralateral disconnection of OFC→DS projections had no effect on oxycodone seeking on abstinence day 1. Together, these results demonstrated a causal role of OFC→DS projections in incubation of oxycodone craving.

The Orbitofrontal Cortex to Striatal Cholinergic Interneuron Circuit Controls Cognitive Flexibility Shaping Alcohol-Seeking Behavior

A top-down neuronal circuit from the orbitofrontal cortex (OFC) to the dorsomedial striatum (DMS) appears to be critical for cognitive flexibility. However, how OFC projections to different types of neurons in the DMS control cognitive flexibility and contribute to substance seeking and use, which are relatively inflexible behaviors, remains unclear. Mice were trained on two-bottle choice and operant alcohol self-administration procedures. The cognitive flexibility of the mice was tested through a place discrimination task. Electrophysiology and in vivo optogenetics were used to test the function of neural circuits in alcohol-seeking behavior. We depicted a connection from the OFC to striatal neurons and found that OFC afferents could elicit functional flexibility in striatal cholinergic interneurons (CINs). A mouse model of chronic alcohol consumption showed impaired cognitive flexibility and reduced burst-pause firing. The impairment of the OFC-DMS circuit resulted in a reduction in glutamatergic transmission in OFC-medium spiny neurons (MSNs) through a CIN-mediated pre-inhibition mechanism. Importantly, remodeling the OFC-DMS circuit by inducing LTP restored cognitive flexibility. Furthermore, CINs were responsible for the impact of remodeling of the OFC-DMS circuit on cognitive flexibility. This regulatory role of CINs preferentially facilitated the potentiation of glutamatergic transmission in D2 receptor-expressing medium spiny neurons (D2-MSNs) but not in D1-MSNs. Finally, activation of the OFC-CIN-D2-MSN circuit decreased alcohol-seeking behavior. Improving OFC-CIN circuit-mediated cognitive flexibility may provide a novel strategy for treating uncontrolled alcohol-seeking behavior.

Abnormal beta bursts of depression in the orbitofrontal cortex and its relationship with clinical symptoms

BackgroundRecent researches have reported that frequency-specific patterns of neural activity contain not only rhythmically sustained oscillations but also transient-bursts of isolated events. The aim of this study was to investigated the correlation between beta burst and depression in order to explore depressive disease and the neurological underpinnings of disease-related symptoms. MethodsWe collected resting-state MEG recordings from 30 depressive patients and a matched 40 healthy controls. A Hidden Markov Model (HMM) was applied on source-space time courses for 78 cortical regions of the AAL atlas and the temporal characteristics of beta burst from the matched HMM states were captured. Group differences were evaluated on these beta burst characteristics after permutation tests and, for the depressive group, associations between burst characteristics and clinical symptom severity were determined using Spearman correlation coefficients. ResultsAt a threshold of p=0.05corrected, burst characteristics revealed significant differences between depression patients and controls at the group level, including increased burst amplitude in frontal lobe, decreased burst duration in occipital regions, increased burst rate and decreased burst interval time in some brain regions. Furthermore, burst amplitude in the orbitofrontal cortex (OFC) was positively related to the severity of sleep disturbance and burst rate in the OFC was negatively related to the severity of anxiety in depression patients. ConclusionsThe findings highlight OFC may be a targeted area responsible for the anxiety and sleep disturbance symptom by abnormal beta burst in depressive patients and beta burst characteristics of OFC might serve as a neuro-marker for the depression.

The Orbitofrontal Cortex Is Required for Learned Modulation of Innate Olfactory Behavior.

Animals have evolved innate responses to cues including social, food, and predator odors. In the natural environment, animals are faced with choices that involve balancing risk and reward where innate significance may be at odds with internal need. The ability to update the value of a cue through learning is essential for navigating changing and uncertain environments. However, the mechanisms involved in this modulation are not well defined in mammals. We have established a new olfactory assay that challenges a thirsty mouse to choose an aversive odor over an attractive odor in foraging for water, thus overriding their innate behavioral response to odor. Innately, mice prefer the attractive odor port over the aversive odor port. However, decreasing the probability of water at the attractive port leads mice to prefer the aversive port, reflecting a learned override of the innate response to the odors. The orbitofrontal cortex (OFC) is a fourth-order olfactory brain area, involved in flexible value association, with behaviorally relevant outputs throughout the limbic system. We performed optogenetic and chemogenetic silencing experiments that demonstrate the OFC is necessary for this learned modulation of innate aversion to odor. Further, we characterized odor evoked c-fos expression in learned and control mice and found significant suppression of activity in the bed nucleus of the stria terminalis, lateral septum, and central and medial amygdala. These findings reveal that the OFC is necessary for the learned override of innate behavior and may signal to limbic structures to modulate innate response to odor.

Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States.

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS- cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), a major reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior.

I feel your pain: higher empathy is associated with higher posterior default mode network activity

Abstract Empathy is characterized as the ability to share one's experience and is associated with altruism. Previous work using blood oxygen level–dependent (BOLD) functional MRI (fMRI) has found that empathy is associated with greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), and self-reference (medial prefrontal cortex; precuneus). However, BOLD fMRI has some limitations that may not reliably capture the tonic experience of empathy. To address this, the present study used a perfusion-based arterial spin labeling fMRI approach that provides direct a quantifiable measurement of cerebral blood flow (1 mL/100 g tissue/min) and is less susceptible to low-frequency fluctuations and empathy-based “carry-over” effects that may be introduced by BOLD fMRI–based block designs. Twenty-nine healthy females (mean age = 29 years) were administered noxious heat (48°C; left forearm) during arterial spin labeling fMRI. In the next 2 fMRI scans, female volunteers viewed a stranger (laboratory technician) and their romantic partner, respectively, receive pain-evoking heat (48°C; left forearm) in real-time and positioned proximal to the scanner during fMRI acquisition. Visual analog scale (0 = “not unpleasant”; 10 = “most unpleasant sensation imaginable”) empathy ratings were collected after each condition. There was significantly (P = 0.01) higher empathy while viewing a romantic partner in pain and greater cerebral blood flow in the right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, and precuneus when compared with the stranger. Higher empathy was associated with greater precuneus and primary visual cortical activation. The present findings indicate that brain mechanisms supporting the embodiment of another's experience is associated with higher empathy.

Neuroimaging meta-analyses reveal convergence of interoception, emotion, and social cognition across neurodegenerative diseases.

Simultaneous interoceptive, emotional, and social cognition deficits are observed across neurodegenerative diseases. Indirect evidence suggests shared neurobiological bases underlying these impairments, termed the allostatic-interoceptive network (AIN). However, no study has yet explored the convergence of these deficits in neurodegenerative diseases or examined how structural and functional changes contribute to cross-domain impairments. A PRISMA Activated Likelihood Estimate (ALE) metanalyses encompassed studies meeting inclusion criteria: interoception, emotion, or social cognition tasks; neurodegenerative diseases (behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasias (PPAs) Alzheimer's disease (AD), Parkinson's Disease (PD), multiple sclerosis (MS)); and neuroimaging (structural: MRI voxel-based morphometry; functional: fMRI and FDG-PET). From 20,593 studies, 170 met inclusion criteria (58 interoception, 65 emotion, and 47 social cognition) involving 7032 participants (4963 patients and 2069 healthy controls). In all participants combined, conjunction analyses revealed AIN involvement of the insula, amygdala, orbitofrontal cortex, anterior cingulate, striatum, thalamus, and hippocampus across domains. In bvFTD this conjunction was replicated across domains, with further involvement of the temporal pole, temporal fusiform cortex, and angular gyrus. A convergence of interoception and emotion in the striatum, thalamus, and hippocampus in PD and the posterior insula in PPAs was also observed. In AD and MS, disruptions in the AIN were observed during interoception, but no convergence with emotion was identified. Neurodegeneration induces dysfunctional AIN across atrophy, connectivity, and metabolism, more accentuated in bvFTD. Findings bolster the predictive coding theories of large-scale AIN, calling for more synergistic approaches to understanding interoception, emotion, and social cognition impairments in neurodegeneration.

Structural development and brain asymmetry in the fronto-limbic regions in preschool-aged children.

Early-life experiences play a crucial role in the development of the fronto-limbic regions, influencing both macro- and microstructural changes in the brain. These alterations profoundly impact cognitive, social-emotional functions. Recently, early limbic structural alterations have been associated with numerous neurological and psychiatric morbidities. Although identifying normative developmental trajectories is essential for determining brain alterations, only a few studies have focused on examining the normative trajectories in the fronto-limbic regions during preschool-aged children. The aim of this study was to investigate the structural-developmental trajectory of the fronto-limbic regions using the cortical thickness, volume, and subcortical volume in 57 healthy and typical preschool-aged children between 1 and 5 years and examined the early lateralization patterns during the development of the fronto-limbic regions. Regarding brain lateralization, remarkable asymmetry was detected in the volume of thalamus and the cortical regions excluding the lateral orbitofrontal cortex in the fronto-limbic regions. This study of preschool-aged children may fill the knowledge gaps regarding the developmental patterns and hemispheric asymmetries of the fronto-limbic regions between newborns and adolescents.

The Role of the Orbitofrontal Cortex in the Regulation of Fear Coping Strategies.

Under threats, individuals exhibit freezing behavior and prepare for active coping. The ability to flexibly shift between freezing and active coping increases survival chances in animals and decreases susceptibility to mental disorders among human beings. For example, patients with psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder, often show maladaptive coping behaviors. The orbitofrontal cortex (OFC) is a critical hub to process higher cognitive functions, sensory inputs, reward learning, and decision-making. It also regulates negative emotions and its aberrant activation level often correlates with numerous mental disorders. The rodent OFC comprises different subdivisions with varying connections to cortical and subcortical regions. Among these subdivisions, the medial orbital area (MO) and the lateral orbital area (LO) have distinct functions in the regulation of fear. Here, we updated the existing rodent literature studying the function of the OFC, with a particular focus on the MO and the LO in different coping strategies of animals. By examining the role of the OFC in the mediation of defensive coping strategies, we aim to deepen the understanding of its functional importance on mental health.

Functional brain alterations in COVID-19 patients using resting-state fMRI: a systematic review.

This study systematically reviews the available evidence on resting-state functional magnetic resonance imaging (rs-fMRI) related to neurological symptoms and cognitive declines in COVID-19 patients. We followed PRISMA guidelines and looked up the PubMed, and Scopus databases for articles search on COVID-19 patients with neurological impairments, and functional connectivity alteration using rs-fMRI technique. Articles published between January 1, 2020, and May 31, 2024, are included in this study. The Quality Assessment Tool for Observational Prospective and Cross-Sectional Studies from the National Heart, Lung, and Blood Institute (NHLBI) was used to assess the quality of papers. A total of 15 articles met the inclusion criteria. The result reveals that the most prevalent neurological impairment associated with COVID-19 was cognitive decline, encompassing issues in attention, memory, processing speed, executive functions, language, and visuospatial ability. The brain connectivity results reveal that two brain areas were functionally altered; the prefrontal cortex and parahippocampus. The functional connectivity mainly increased in the frontal, temporal, and anterior piriform cortex, and reduced in the cerebellum, superior orbitofrontal cortex, and middle temporal gyrus, which also correlated with cognitive decline. The findings of neurological symptoms indicate one study reported a Disorder of Consciousness (DoC), and four studies reported COVID-19 patients with olfactory dysfunction. The present study concludes that COVID-19 can alter brain functional connectivity and offers significant insight into how COVID-19 affects the neuronal foundation of cognitive decline and other neurological impairments.