Episodic Memory, Hippocampal Volume, and Function for Classification of Mild Cognitive Impairment Patients Regarding Amyloid Pathology.

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-ß (Aß) deposition which is the hallmark for early identification of the Alzheimer's disease continuum. OBJECTIVE: We investigated the role of Aß 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 Aß PET PIB positive (PIB+) aMCI (N = 17), Aß 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 Aß deposition.

Corrigendum: Behavioral and Neural Correlates of Cognitive Training and Transfer Effects in Stroke Patients.

[This corrects the article DOI: 10.3389/fneur.2020.01048.].

Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series.

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.

Behavioral and Neural Correlates of Cognitive Training and Transfer Effects in Stroke Patients.

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.

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain

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.

Precision non-implantable neuromodulation therapies: a perspective for the depressed brain.

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.

Effects of semantic categorization strategy training on episodic memory in children and adolescents.

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.

Effects of Mnemonic Strategy Training on Brain Activity and Cognitive Functioning of Left-Hemisphere Ischemic Stroke Patients.

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.

Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Trial.

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.

Brain regions supporting verbal memory improvement in healthy older subjects.

UNLABELLED: Despite growing interest in developing cognitive training interventions to minimize the aging cognitive decline process, no studies have attempted to explore which brain regions support the application of semantic strategies during verbal memory encoding. Our aim was to investigate the behavioral performance and brain correlates of these strategies in elderly individuals using fMRI in healthy older subjects. METHOD: Subjects were scanned twice on the same day, before and after, directed instructions to apply semantic strategies during the encoding of word lists. RESULTS: Improved memory performance associated to increased semantic strategy application and brain activity in the left inferior and middle and right medial superior prefrontal cortex were found after the directed instructions. There was also reduced activation in areas related to strategy mobilization. CONCLUSION: Improved memory performance in older subjects after the application of semantic strategies was associated with functional brain reorganization involving regions inside and outside the typical memory network.

Brain regions supporting verbal memory improvement in healthy older subjects / Regiões do cérebro relacionadas à melhora da memória verbal em idosos saudáveis

Despite growing interest in developing cognitive training interventions to minimize the aging cognitive decline process, no studies have attempted to explore which brain regions support the application of semantic strategies during verbal memory encoding. Our aim was to investigate the behavioral performance and brain correlates of these strategies in elderly individuals using fMRI in healthy older subjects. Method Subjects were scanned twice on the same day, before and after, directed instructions to apply semantic strategies during the encoding of word lists. Results Improved memory performance associated to increased semantic strategy application and brain activity in the left inferior and middle and right medial superior prefrontal cortex were found after the directed instructions. There was also reduced activation in areas related to strategy mobilization. Conclusion Improved memory performance in older subjects after the application of semantic strategies was associated with functional brain reorganization involving regions inside and outside the typical memory network. .

Apesar do crescente interesse em intervenções de treinamento cognitivo para minimizar o declínio cognitivo do envelhecimento, nenhum estudo explorou quais regiões do cérebro estão relacionadas à aplicação de estratégias semânticas durante a codificação da memória verbal. Nosso objetivo foi investigar o comportamento e correlatos cerebrais associados a essas estratégias usando fMRI em idosos saudáveis. Método Os sujeitos foram examinados no mesmo dia, antes e depois, de instruções dirigidas para aplicar estratégias semânticas durante a codificação de palavras. Resultados Melhora da memória relacionada ao uso de estratégias semânticas e aumento da atividade no córtex prefrontal inferior e medial esquerdo e medial superior direito foram encontrados após as instruções. Também houve redução de ativação em áreas de mobilização de estratégias. Conclusão A melhora da memória em idosos após o uso de estratégias semânticas estava associada à reorganização cerebral funcional envolvendo regiões dentro e fora da rede de áreas cerebrais típicas da memória. .

Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

"Salt and pepper" in the eye and face: a prelude to brainstem ischemia.

PURPOSE: To report the "salt and pepper"(SP) eye pain as a herald symptom of pontine ischemia. DESIGN: Observational case series. METHODS: We reviewed clinical and neuroimaging findings of four patients who presented initially with the sensation of SP in the eyes and then developed paramedian pontine infarcts confirmed by neuroimaging. RESULTS: All of the patients developed other neurologic symptoms or signs, either in association with the sensation of SP in the eyes, from hours to days later. Magnetic resonance imaging (MRI) showed paramedian pontine infarcts in all of the patients and angiography showed basilar artery occlusive disease in three of them. CONCLUSION: Impending pontine ischemia is an important differential diagnosis in patients with acute ocular pain. Prompt neurovascular evaluation and treatment may avoid devastating brainstem infarcts that cause death or long-term disability, particularly in patients with basilar artery occlusive disease.