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Dizziness and vertigo, frequently associated with cerebrovascular origins, pose a substantial challenge in emergency medical settings due to their potential to be associated with severe underlying conditions. Sudden-onset dizziness, in particular, may be an early indicator of critical events such as stroke or transient ischemic attack. This comprehensive review encompasses the differential diagnosis of central causes of dizziness and vertigo, emphasizing the crucial role of imaging modalities in the accurate detection and assessment, including cerebrovascular diseases, inflammatory disorders, infections, and other conditions such as vestibular migraine and cervical spondylosis. It highlights the significance of advanced imaging techniques, particularly magnetic resonance imaging and computed tomography in identifying and distinguishing these conditions., (Copyright © 2024. Published by Elsevier Inc.)

The intricate anatomy and embryology of the middle ear, labyrinth, and vertigo-related intracranial pathways involve complex developmental processes and contributions from multiple germ layers. The middle ear, comprised of the tympanic cavity, ossicles, and Eustachian tube, develops from the first and second branchial arches and clefts. In contrast, the inner ear originates from the otic vesicle, forming the bony and membranous labyrinths. The embryological timeline spans from the 40th day of gestation to the 24th week. The vestibulocochlear nerve (VIII cranial nerve) emerges with the inner ear structures and is essential for auditory and vestibular functions. The brainstem integrates sensory inputs from the labyrinth through various nuclei and pathways, contributing to balance and spatial awareness. This review highlights the critical developmental stages and anatomical details relevant to understanding auditory and vestibular system disorders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study of an Ischemic stroke infarction allows verifying how the lesion produces alterations in the neuronal networks resulting in cognitive deficits. It also allows the verification of adaptive and maladaptive cerebral reorganization related to the injury. In our previous fMRI study, we found that patients without ischemic vascular lesions in left inferior frontal gyrus showed an efficient compensation mechanism during the associative encoding of face name pairs, by the increased activation of ventrolateral and dorsolateral areas of contralesional hemisphere associated with better memory performance. While patients with ischemic vascular lesions on left inferior frontal gyrus (IFG) demonstrated worse memory performance and no signs of compensation mechanism. The present study explores more of these findings by analyzing perilesional and contralesional activations related to unfamiliar face name associative encoding in adults with chronic ischemic stroke, with or without left IFG lesion, compared to healthy controls. The main results showed that stroke survivors without lesions in IFG demonstrated increased activation in perilesional and contralesional prefrontal regions associated with better associative memory recognition, which are indicative of adaptive compensatory mechanisms. However, they also showed a negative correlation between the activation of right anterior prefrontal and inferior parietal regions and the associative memory performance, which may indicate the presence of maladaptive interhemispheric disinhibition. On the other hand, stroke survivors with IFG lesions demonstrated negative correlations in activations of the ipsilesional inferior parietal cortex and positive correlations in activations of the left middle frontal gyrus and left precentral cortex, which demonstrate the simultaneous occurrence of adaptive and maladaptive brain reorganization mechanisms in this group. However, the increase in perilesional prefrontal regions, associated with bilateral activation of the hippocampus and amygdala, was not enough to compensate for the inefficiency of associative memory performance. Finally, the differences in activation observed in stroke survivors reflect their clinical heterogeneity and demonstrate that adaptive or maladaptive compensatory mechanisms can coexist in the same group of patients. Furthermore, they reinforce the importance of the left IFG in the associative encoding of unfamiliar face name pairs and may suggest a deficit in associative memory related to injury in this region., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization., Methods: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries., Results: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome)., Discussion: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design., (© 2023 the Alzheimer's Association.)

Background: The coronary calcium score (CAC) measured on chest computerized tomography is a risk marker of cardiac events and mortality. We compared CAC scores in two multiethnic groups without symptomatic coronary artery disease: subjects in the chronic phase after stroke or transient ischemic attack and at least one symptomatic stenosis ≥50% in the carotid or vertebrobasilar territories (Group athero ) and a control group (Group control )., Methods: In this cross-sectional study, Group athero included two subgroups: Group ExtraorIntra , with stenoses in either cervical or intracranial arteries, and Group Extra&Intra , with stenoses in at least one cervical and one intracranial artery. Group control had no history of prior stroke/transient ischemic attacks and no stenoses ≥50% in cervical or intracranial arteries. Age and sex were comparable in all groups. Frequencies of CAC ≥100 and CAC > 0 were compared between Group athero and Group control , as well as between Group ExtraorIntr , Group Extra&Intra , and Group control , with bivariate logistic regressions. Multivariate analyses were also performed., Results: A total of 120 patients were included: 80 in Group athero and 40 in Group control. CAC >0 was significantly more frequent in Group athero (85%) than Group control (OR, 4.19; 1.74-10.07; p = 0.001). Rates of CAC ≥100 were not significantly different between Group athero and Group control but were significantly greater in Group Extra&Intra ( n = 13) when compared to Group control (OR 4.67; 1.21-18.04; p = 0.025). In multivariate-adjusted analyses, "Group athero " and "Group Extra&Intra " were significantly associated with CAC., Conclusion: The frequency of coronary calcification was higher in subjects with stroke caused by large-artery atherosclerosis than in controls., Competing Interests: RS has received honoraria related to consulting, research and or speaker activities from: Amgen, Aché, Astra Zeneca, Esperion, Kowa, Merck, Novo-Nordisk, PTC, Pfizer, and Sanofi/Regeneron. MB has received speaker fees from GE healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Araújo, Santos, Bittencourt, Dantas, Oshiro, Nomura, Bor-Seng-Shu, Oliveira, Leite, Martin, Alves, Silva, Silva and Conforto.)

Background: Approximately 10% of adolescents worldwide are overweight or obese, hence the urgent and universal need to elucidate possible mechanisms that lead to obesity in the adolescent population., Objectives: We examined the hypothalamic metabolism and its relationship with physical development in obese and eutrophic adolescents., Methods: We performed a case-control study with 115 adolescents between 11 and 18 years of age, to compare obese (BMI z-score ≥ 2) and nonobese individuals (eutrophic controls; BMI z-score ≤ 1). The following hypothalamic metabolite ratios were examined as primary outcomes: glutamate/creatine (Cr), the sum of glutamate and glutamine/Cr, N-acetylaspartate (NAA)/Cr, myoinositol/Cr, and total choline/Cr (glycerophosphocholine +  phosphocholine/Cr), quantified by magnetic resonance spectroscopy. BMI z-scores, pubertal status, and scores on the Yale Food Addiction Scale, the Binge Eating Scale, and the Child Depression Inventory were assessed as secondary outcomes. Pearson coefficients (r) or nonparametric Spearman correlation (rho) analyses were performed between hypothalamic metabolite ratios and other parameters, such as BMI z-scores, physical development, food habits, depression symptoms, and serum protein concentrations (cytokines, hormones, and neuropeptides)., Results: Adolescents with obesity showed a lower hypothalamic NAA/Cr ratio (0.70 ± 0.19) compared to their eutrophic counterparts (0.84 ± 0.20; P = 0.004). The NAA/Cr ratio was negatively correlated with BMI z-scores (r = -0.25; P = 0.03) and serum insulin (rho = -0.27; P = 0.04), C-peptide (rho = -0.26; P = 0.04), amylin (r = -0.27; P = 0.04), ghrelin (rho = -0.30; P = 0.02), and neuropeptide Y (r = -0.27; P = 0.04). Also, the NAA/Cr ratio was positively correlated with circulating IL-8 levels (rho = 0.26; P = 0.04)., Conclusions: High BMI z-scores are associated with lower hypothalamic NAA/Cr ratios. The negative correlations found between the NAA/Cr ratio and serum cytokines, hormones, and neuropeptides suggest a broad cross-talk linking hormonal imbalances, neurohumoral alterations, and hypothalamic functions in adolescents with obesity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Brain abnormalities are a concern in COVID-19, so we used minimally invasive autopsy (MIA) to investigate it, consisting of brain 7T MR and CT images and tissue sampling via transethmoidal route with at least three fragments: the first one for reverse transcription polymerase chain reaction (RT-PCR) analysis and the remaining fixed and stained with hematoxylin and eosin. Two mouse monoclonal anti-coronavirus (SARS-CoV-2) antibodies were employed in immunohistochemical (IHC) reactions., Results: Seven deceased COVID-19 patients underwent MIA with brain MR and CT images, six of them with tissue sampling. Imaging findings included infarcts, punctate brain hemorrhagic foci, subarachnoid hemorrhage and signal abnormalities in the splenium, basal ganglia, white matter, hippocampi and posterior cortico-subcortical. Punctate brain hemorrhage was the most common finding (three out of seven cases). Brain histological analysis revealed reactive gliosis, congestion, cortical neuron eosinophilic degeneration and axonal disruption in all six cases. Other findings included edema (5 cases), discrete perivascular hemorrhages (5), cerebral small vessel disease (3), perivascular hemosiderin deposits (3), Alzheimer type II glia (3), abundant corpora amylacea (3), ischemic foci (1), periventricular encephalitis foci (1), periventricular vascular ectasia (1) and fibrin thrombi (1). SARS-CoV-2 RNA was detected with RT-PCR in 5 out of 5 and IHC in 6 out 6 patients (100%)., Conclusions: Despite limited sampling, MIA was an effective tool to evaluate underlying pathological brain changes in deceased COVID-19 patients. Imaging findings were varied, and pathological features corroborated signs of hypoxia, alterations related to systemic critically ill and SARS-CoV-2 brain invasion., (© 2022. The Author(s).)

Background: Previous studies of hippocampal function and volume related to episodic memory deficits in patients with amnestic mild cognitive impairment (aMCI) have produced mixed results including increased or decreased activity and volume. However, most of them have not included biomarkers, such as amyloid-β (Aβ) deposition which is the hallmark for early identification of the Alzheimer's disease continuum., Objective: We investigated the role of Aβ deposition, functional hippocampal activity and structural volume in aMCI patients and healthy elderly controls (HC) using a new functional MRI (fMRI) ecological episodic memory task., Methods: Forty-six older adults were included, among them Aβ PET PIB positive (PIB+) aMCI (N = 17), Aβ PET PIB negative (PIB-) aMCI (N = 15), and HC (N = 14). Hippocampal volume and function were analyzed using Freesurfer v6.0 and FSL for news headlines episodic memory fMRI task, and logistic regression for group classification in conjunction with episodic memory task and traditional neuropsychological tests., Results: The aMCI PIB+ and PIB-patients showed significantly worse performance in relation to HC in most traditional neuropsychological tests and within group difference only on story recall and the ecological episodic memory fMRI task delayed recall. The classification model reached a significant accuracy (78%) and the classification pattern characterizing the PIB+ included decreased left hippocampal function and volume, increased right hippocampal function and volume, and worse episodic memory performance differing from PIB-which showed increased left hippocampus volume., Conclusion: The main findings showed differential neural correlates, hippocampal volume and function during episodic memory in aMCI patients with the presence of Aβ deposition.

Objective: To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center., Methods: We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020., Results: Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001)., Conclusion: In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.

Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay., Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis., Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil., Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases., Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

Introduction: Mnemonic strategy training (MST) has been shown to improve cognitive performance and increase brain activation in those with mild cognitive impairment (MCI). However, little is known regarding the effects of MST on functional connectivity (FC) at rest. The aim of the present study was to investigate the MST focused on face-name associations effect on resting-state FC in those with MCI., Methods: Twenty-six amnestic MCI participants were randomized in MST (N = 14) and Education Program (active control; N = 12). Interventions occurred twice a week over two consecutive weeks (ie, four sessions). Resting-state functional magnetic resonance imaging was collected at pre- and post-intervention. Regions of interest (ROIs) were selected based on areas that previously showed task-related activation changes after MST. Changes were examined through ROI-to-ROI analysis and significant results were corrected for multiple comparisons., Results: At post-intervention, only the MST group showed increased FC, whereas the control group showed decreased or no change in FC. After MST, there was an increased FC between the left middle temporal gyrus and right orbitofrontal cortex. In addition, a time-by-group interaction indicated that the MST group showed greater increased FC between the right inferior frontal gyrus and left brain regions, such as fusiform gyrus, temporal pole, and orbitofrontal cortex relative to controls., Discussion: MST enhanced FC in regions that are functionally relevant for the training; however, not in all ROIs investigated. Our findings suggest that MST-induced changes are reflected in task-specific conditions, as previously reported, but also in general innate connectivity. Our results both enhance knowledge about the mechanisms underlying MST effects and may provide neurophysiological evidence of training transfer., Competing Interests: No author has any conflict of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Stroke lesions are frequently followed by cognitive impairments. Cognitive training is a non-pharmacological intervention that can promote neural compensation mechanisms and strategies to remediate cognitive impairments. The aims of this study were: (1) To investigate the cognitive performance, generalization effects, and neural correlates of semantic organization strategy training (SOST) in patients with chronic left frontoparietal stroke and healthy controls (HC); and (2) to compare the behavioral effects and neural correlates of SOST with an active control psychoeducation intervention (PI). In this randomized controlled study, all participants were randomly allocated into two groups, one group received SOST, and the other received PI intervention. Participants underwent two fMRI sessions, one prior and the other, after intervention. In each fMRI session, images were obtained during memory encoding task using a list of semantically related words. We found improved post-intervention memory performance in participants that received SOST (both patients and controls), indicated by number of words recalled, word clustering scores, and performance in a generalization task. The fMRI analysis revealed negative correlation between task performance and regions of the default-mode network. These results suggest that cognitive training using semantic organization strategy can improve episodic memory performance and promote potential functional neuroplasticity in patients with ischemic stroke lesions. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03644290., (Copyright © 2020 Miotto, Bazán, Batista, Conforto, Figueiredo, Martin, Avolio, Amaro and Teixeira.)

Prior work has revealed that mnemonic strategy training (MST) can enhance memory for specific content and engages regions in the frontoparietal cognitive control network. Evidence of transfer to novel content is less clear. Here, we provide secondary analysis of functional magnetic resonance imaging (fMRI) data acquired during a randomized controlled trial that compared MST to an active education control condition in patients with amnestic mild cognitive impairment (a-MCI). In the trial, thirty participants with a-MCI were randomized to the education program (EP) or MST, where they learned to apply the technique to face-name associations during four intervening hour long training sessions. Participants underwent pre- and post-training fMRI scans, during which they encoded both the trained (i.e., those used during the four training sessions) and untrained ('novel') face-name associations. The primary cognitive outcome measures revealed significantly improved memory for both trained and novel stimuli - effects supporting near transfer of MST. Relative to pre-training, there were significant and highly similar increases in activation for both trained and novel stimuli, especially in regions associated with the frontoparietal cognitive control network bilaterally, but also in temporal areas related to social cognition and emotional processing. Critically, this pattern of activation was notably different from the EP group. Thus, the changes in activation were consistent with the strategies trained and, combined with the cognitively-based near transfer effects, suggest that MST focused on face-name association enhances performance by engaging cognitive control and social/emotional processing. Finally, our data indicated that our MST is a relevant and efficient intervention to a-MCI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Episodic memory is the ability to learn, store and recall new information. The prefrontal cortex (PFC) is a crucial area engaged in this ability. Cognitive training has been demonstrated to improve episodic memory in adults and older subjects. However, there are no studies examining the effects of cognitive training on episodic memory encoding in typically developing children and adolescents. This study investigated the behavioral effects and neural correlates of semantic categorization strategy training in children and adolescents during verbal episodic memory encoding using functional magnetic resonance imaging (fMRI). Participants with age range: 7-18 years were scanned before and after semantic categorization training during encoding of word lists. Results showed improved memory performance in adolescents, but not in children. Deactivation of the anterior medial PFC/anterior cingulate and higher activation of the right anterior and lateral orbital gyri, right frontal pole and right middle frontal gyrus activation were found after training in adolescents when compared to children. These findings suggest different maturational paths of brain regions, especially in the PFC, and deactivation of default mode network areas, which are involved in successful memory and executive processes in the developing brain., Competing Interests: The authors have declared that no competing interests exist.

Memory dysfunction is one of the main cognitive impairments caused by stroke, especially associative memory. Therefore, cognitive training, such as face-name mnemonic strategy training, could be an important intervention for this group of patients. The goal of this study was to evaluate the behavioral effects of face-name mnemonic strategy training, along with the neural substrate behind these effects, in the left frontoparietal lobe stroke patients. Volunteers underwent 2 sessions of functional magnetic resonance imaging (fMRI) during face-name association task: one prior and the other after the cognitive training. The fMRI followed a block design task with three active conditions: trained face-name pairs, untrained face-name pairs, and a couple of repeated face-name pairs. Prior to each fMRI session, volunteers underwent neuropsychological assessment. Training resulted in better performance on delayed memory scores of HVLT-R, and on recognition on a generalization strategy task, as well as better performance in the fMRI task. Also, trained face-name pairs presented higher activation after training in default-mode network regions, such as the posterior cingulate cortex, precuneus, and angular gyrus, as well as in lateral occipital and temporal regions. Similarly, untrained face-name pairs also showed a nonspecific training effect in the right superior parietal cortex, right supramarginal gyrus, anterior intraparietal sulcus, and lateral occipital cortex. A correlation between brain activation and task performance was also found in the angular gyrus, superior parietal cortex, anterior intraparietal sulcus, and lateral occipital cortex. In conclusion, these results suggest that face-name mnemonic strategy training has the potential to improve memory performance and to foster brain activation changes, by the recruitment of contralesional areas from default-mode, frontoparietal, and dorsal attention networks as a possible compensation mechanism.

Background: Mnemonic strategy training (MST) has been shown to improve cognitive performance in amnestic mild cognitive impairment (a-MCI), however, several questions remain unresolved. The goal of the present study was to replicate earlier pilot study findings using a randomized controlled design and to evaluate transfer effects and changes in brain activation. Methods: Thirty patients with a-MCI were randomized into MST or education program. At baseline, participants completed clinical and neuropsychological assessments as well as structural and functional magnetic resonance imaging (fMRI). Interventions were administered individually and comprised four sessions, over 2 weeks. MST taught patients to use a three-step process to learn and recall face-name associations. Post-treatment assessment included fMRI, a separate face-name association task, neuropsychological tests, and measures of metamemory. Behavioral (i.e., non-fMRI) measures were repeated after one and 3-months. Results: Participants in the MST condition showed greater improvement on measures of face-name memory, and increased associative strategy use; effects that were accompanied by increased fMRI activation in the left anterior temporal lobe. While all participants reported greater contentment with their everyday memory following intervention, only the MST group reported significant improvements in their memory abilities. There was no clear indication of far-transfer effects to other neuropsychological tests. Conclusion: Results demonstrate that patients with a-MCI not only show stimulus specific benefits of MST, but that they appear capable of transferring training to at least some other cognitive tasks. MST also facilitated the use of brain regions that are involved in face processing, episodic and semantic memory, and social cognition, which are consonant with the cognitive processes engaged by training.