Diffusion-weighted imaging measurements of central smell regions in COVID-19 patients: insular gyrus, corpus amygdala, and thalamus.

OBJECTIVE: The aim of this study was to investigate central smell centers with cranial magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in COVID-19. PATIENTS AND METHODS: This retrospective study evaluated cranial MRI images of 54 adults. The experimental group (Group 1), consisting of 27 patients with positive COVID-19 real-time polymerase chain reaction (RT-PCR) assays, was compared to the control group (Group 2), comprising 27  healthy controls without COVID-19. The apparent diffusion coefficient (ADC) values were measured in the corpus amygdala, thalamus, and insular gyrus in both groups. RESULTS: Thalamus ADC values of the COVID-19 group were significantly lower compared to the control group bilaterally. However, no differences were found in the insular gyrus and corpus amygdala ADC values between the two groups. Positive correlations were observed between the insular gyrus and corpus amygdala ADC values and the thalamus ADC values. Insular gyrus ADC values (right) were higher in females. Left insular gyrus and corpus amygdala ADC values were higher in COVID-19 patients with smell loss. Right insular gyrus and left corpus amygdala ADC values were lower in COVID-19 patients with lymphopenia. CONCLUSIONS: Diffusion restriction in olfactory areas can be considered an obvious indicator that the COVID-19 virus affects and damages the immune system at the neuronal level. Given the urgency and lethality of the current pandemic, acute onset odor loss should be considered a high suspicion-adhesive index for patients with SARS-CoV-2 infection. Therefore, the sense of smell should be considered and evaluated simultaneously with other neurological symptoms. DWI should be widely used as an early imaging method for central nervous system (CNS) infections, especially in relation to COVID-19.

Effects of COVID-19 pandemic on structural brain development in early adolescence.

The COVID-19 pandemic caused a global health crisis with large behavioral effects and serious stress and social consequences. Particularly, teenagers suffered pandemic-related social restrictions including school closures. This study examined whether and how structural brain development was influenced by the COVID-19 pandemic and whether pandemic length was associated with accumulating or resilience effects of brain development. We investigated structural changes in social brain regions (medial prefrontal cortex: mPFC; temporoparietal junction: TPJ) as well as the stress-related hippocampus and amygdala, using a longitudinal design of 2 MRI waves. We selected two age-matched subgroups (9-13 years old), one was tested before (n = 114) and the other during (peri-pandemic group, n = 204) the COVID-19 pandemic. Results indicated that teenagers in the peri-pandemic group showed accelerated development in the mPFC and hippocampus compared to the before-pandemic group. Furthermore, TPJ growth showed immediate effects followed by possibly subsequent recovery effects that returned to a typical developmental pattern. No effects were observed for the amygdala. The findings of this region-of-interest study suggest that experiencing the COVID-19 pandemic measures had accelerating effects on hippocampus and mPFC development but the TPJ showed resilience to negative effects. Follow-up MRI assessments are needed to test acceleration and recovery effects over longer periods.

Ventromedial prefrontal cortex activity differentiates sick from healthy faces: Associations with inflammatory responses and disease avoidance motivation.

BACKGROUND: Humans are able to discern the health status of others using olfactory and visual cues, and subsequently shift behavior to make infection less likely. However, little is known about how this process occurs. The present study examined the neural regions involved in differentiating healthy from sick individuals using visual cues. METHODS: While undergoing a functional magnetic resonance imaging scan, participants (N = 42) viewed facial photos of 30 individuals (targets) who had been injected with an inflammatory challenge--low-dose endotoxin (i.e., sick) or placebo (i.e., healthy), and rated how much they liked each face. We examined regions implicated in processing either threat (amygdala, anterior insula) or cues that signal safety (ventromedial prefrontal cortex [VMPFC]), and how this activity related to their liking of targets and cytokine levels (interleukin-6, tumor necrosis factor-α) exhibited by the targets. RESULTS: Photos of sick faces were rated as less likeable compared to healthy faces, and the least liked faces were those individuals with the greatest inflammatory response. While threat-related regions were not significantly active in response to viewing sick faces, the VMPFC was more active in response to viewing healthy (vs. sick) faces. Follow-up analyses revealed that participants tended to have lower VMPFC activity when viewing the least liked faces and the faces of those with the greatest inflammatory response. CONCLUSIONS: This work builds on prior work implicating the VMPFC in signaling the presence of safe, non-threatening visual stimuli, and suggests the VMPFC may be sensitive to cues signaling relative safety in the context of pathogen threats.

Brain reactivity to humorous films is affected by insomnia.

STUDY OBJECTIVES: Emotional reactivity to negative stimuli has been investigated in insomnia, but little is known about emotional reactivity to positive stimuli and its neural representation. METHODS: We used 3 Tesla functional magnetic resonance imaging (fMRI) to determine neural reactivity during the presentation of standardized short, 10- to 40-seconds, humorous films in patients with insomnia (n = 20, 18 females, aged 27.7 +/- 8.6 years) and age-matched individuals without insomnia (n = 20, 19 females, aged 26.7 +/- 7.0 years) and assessed humor ratings through a visual analog scale. Seed-based functional connectivity was analyzed for the left and right amygdalas (lAMYG and rAMYG, respectively) networks: group-level mixed-effects analysis (FLAME; FMRIB Software Library [FSL]) was used to compare amygdala connectivity maps between groups. RESULTS: fMRI seed-based analysis of the amygdala revealed stronger neural reactivity in patients with insomnia than in controls in several brain network clusters within the reward brain network, without humor rating differences between groups (p = 0.6). For lAMYG connectivity, cluster maxima were in the left caudate (Z = 3.88), left putamen (Z = 3.79), and left anterior cingulate gyrus (Z = 4.11), whereas for rAMYG connectivity, cluster maxima were in the left caudate (Z = 4.05), right insula (Z = 3.83), and left anterior cingulate gyrus (Z = 4.29). Cluster maxima of the rAMYG network were correlated with hyperarousal scores in patients with insomnia only. CONCLUSIONS: The presentation of humorous films leads to increased brain activity in the neural reward network for patients with insomnia compared with controls, related to hyperarousal features in patients with insomnia, in the absence of humor rating group differences. These novel findings may benefit insomnia treatment interventions. CLINICAL TRIAL: The Sleepless Brain: Neuroimaging Support for a Differential Diagnosis of Insomnia (SOMNET). ClinicalTrials.gov identifier: NCT02821234; https://clinicaltrials.gov/ct2/show/NCT02821234.

Functional connectivity of amygdala subregions predicts vulnerability to depression following the COVID-19 pandemic.

BACKGROUND: The amygdala is vital in processing psychological stress and predicting vulnerability or resilience to stress-related disorders. This study aimed to build the link between functional magnetic resonance imaging data obtained before the stress event and the subsequent stress-related depressive symptoms. METHODS: Neuroimaging data obtained before the coronavirus disease 2019 pandemic from 39 patients with major depressive disorder (MDD) and 61 health controls (HCs) were used in this study. The participants were divided retrospectively into four groups in accordance with the severity of depressive symptoms during the pandemic: remitted patients, non-remitted patients, depressed HCs (HCd) and non-depressed HCs (HCnd). Seed-based resting-state functional connectivity (rsFC) analyses of the amygdala and its subregions, including the centromedial (CM), the basolateral and the superficial (SF), were performed. RESULTS: Vulnerability to depression was suggested by decreased rsFC between the left CM amygdala and the bilateral lingual gyrus in the HCd group compared with the HCnd group, and decreased rsFC of the left CM or right SF amygdala with the precuneus and the postcentral gyrus in the HCd group compared with patients with MDD. No evidence supported the rsFC of the amygdala or its subregions as a biomarker for the resilience of patients with MDD to stress under antidepressant treatment. LIMITATIONS: Smaller sample size and no longitudinal neuroimaging data. CONCLUSIONS: Our findings suggested that the rsFC of amygdala subregions may represent a neurobiological marker of vulnerability to depression following stress.

COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia.

OBJECTIVE: To describe a novel case of coronavirus disease 2019 (COVID-19)-associated acute necrotizing encephalopathy (ANE) in a patient with aplastic anemia where there was early brain stem-predominant involvement. METHODS: Evaluation of cause, clinical symptoms, and treatment response. RESULTS: A 59-year-old woman with a background of transfusion-dependent aplastic anemia presented with seizures and reduced level of consciousness 10 days after the onset of subjective fever, cough, and headache. Nasopharyngeal swab testing for severe acute respiratory syndrome coronavirus (SARS-CoV-2) was positive, and CT during admission demonstrated diffuse swelling of the brain stem. She required intubation and mechanical ventilation for airway protection, given her reduced level of consciousness. The patient's condition deteriorated, and MRI on day 6 demonstrated worsening brain stem swelling with symmetrical hemorrhagic lesions in the brain stem, amygdalae, putamina, and thalamic nuclei. Appearances were consistent with hemorrhagic ANE with early brain stem involvement. The patient showed no response to steroid therapy and died on the eighth day of admission. CONCLUSIONS: COVID-19 may be associated with an acute severe encephalopathy and, in this case, was considered most likely to represent an immune-mediated phenomenon. As the pandemic continues, we anticipate that the spectrum of neurologic presentation will broaden. It will be important to delineate the full clinical range of emergent COVID-19-related neurologic disease.