Perilesional and contralesional brain activations related to associative encoding of unfamiliar face-names pairs in adults with left chronic stroke with or without ischemic infarct on left inferior frontal gyrus.

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.

Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

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

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

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.

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.

Resting state functional connectivity and neural correlates of face-name encoding in patients with ischemic vascular lesions with and without the involvement of the left inferior frontal gyrus.

Face-name association is a relevant ability for social interactions and involves the ventral and dorsolateral prefrontal cortices, particularly in the left hemisphere, bilateral hippocampal, fusiform gyrus and occipital regions. Previous studies demonstrated the primary role of the hippocampus for this ability in healthy subjects. However, no study has examined the participation of the left inferior frontal area, specially the left inferior frontal gyrus (LIFG) in patients with ischemic vascular lesions. In the present study we addressed this issue and investigated the neural correlates and resting state functional connectivity of face-name memory encoding in ischemic patients with LIFG or without lesions in the left IFG (nLIFG) and healthy controls (HC) using fMRI. The main results showed that the nLIFG group demonstrated efficient compensation related to encoding and performance on face-name learning and recognition memory task, in addition to similar brain areas activated during task performance compared to healthy controls. Some of these areas were more activated in nLIFG group, indicating a compensation mechanism. In contrast, the LIFG group showed worse behavior performance, and no signs of an efficient compensation mechanism. Functional connectivity analysis suggested that the left IFG region seems to be important for maintaining the connectivity of the right fusiform gyrus or, perhaps, lesion in this area is associated to maladaptive reorganization. Our findings highlight the relevant role of the left IFG in face-name learning and encoding, possibly as a primary region in addition to the bilateral hippocampal formation and fusiform gyrus.

Neurophysiologic and Cognitive Changes Arising from Cognitive Training Interventions in Persons with Mild Cognitive Impairment: A Systematic Review.

Background: Previous reviews have generally reported cognitive//behavioral improvements after cognitively oriented treatments (COTs) in persons with MCI. However, comparatively little is known about the neural mechanisms associated with such cognitive improvement. Objective: The primary aim of the current review was to examine neurophysiological changes measured by functional magnetic resonance imaging (fMRI) and possible cognitive changes following COTs in those with MCI. Methods. An extensive literature search was conducted up to August 2018. Inclusion criteria were (1) studies that evaluated the effects of the COTs in patients with amnestic single- or multiple-domain MCI using fMRI, (2) the MCI patient sample having met Petersen's or Jack/Bond's criteria, (3) randomized and/or controlled trials, (4) fMRI and cognitive assessments completed pre- and post-intervention, and (5) articles available in English. Results: Amongst the 26 articles found, 7 studies were included according to the above inclusion criteria. A total of 3 studies applied rehearsal-based strategies as the primary intervention, all of which used computerized cognitive training. Four studies used fMRI to investigate the neurophysiologic and cognitive changes associated with memory strategy training. The majority of the studies included in this review showed evidence of improved objective cognitive performance associated with COTs, even in tasks similar to everyday life activities. In addition, there were significant changes in brain activation associated with interventions, in both typical and atypical brain areas and networks related to memory. Conclusions: Although additional studies are needed given the small sample size, these initial findings suggest that cognitive improvement after COTs is generally associated with both compensatory (i.e., engaging alternative brain regions or networks not "typically" engaged) and restorative (i.e., reengaging the "typical" brain regions or networks) mechanisms.

Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.

OBJECTIVE: Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. METHOD: A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. RESULTS: The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). CONCLUSION: Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.

Differences in prefrontal cortex activation and deactivation during strategic episodic verbal memory encoding in mild cognitive impairment.

In this study we examined differences in fMRI activation and deactivation patterns during episodic verbal memory encoding between individuals with MCI (n = 18) and healthy controls (HCs) (n = 17). Participants were scanned in two different sessions during the application of self-initiated or directed instructions to apply semantic strategies at encoding of word lists. MCI participants showed reduced free recall scores when using self-initiated encoding strategies that were increased to baseline controls' level after directed instructions were provided. During directed strategic encoding, greater recruitment of frontoparietal regions was observed in both MCI and control groups; group differences between sessions were observed in the ventromedial prefrontal cortex and the right superior frontal gyrus. This study provides evidence suggesting that differences of activity in these regions may be related to encoding deficits in MCI, possibly mediating executive functions during task performance.

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.

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

OBJECTIVE: Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. METHODS: Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. RESULTS: After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. CONCLUSION: The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy.

Corpus callosum microstructural changes correlate with cognitive dysfunction in early stages of relapsing-remitting multiple sclerosis: axial and radial diffusivities approach.

The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes.

Cognitive impairments in patients with low grade gliomas and high grade gliomas.

OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

Cognitive impairments in patients with low grade gliomas and high grade gliomas / Comprometimentos cognitivos em pacientes com gliomas de baixo grau e gliomas de alto grau

OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

OBJETIVO: A associação entre tumores cerebrais e déficits cognitivos é bem estabelecida na literatura. No entanto, estudos sobre a cognição de pacientes com gliomas de baixo e alto grau são escassos, especialmente, em sujeitos com baixa escolaridade. Este estudo investigou o funcionamento cognitivo de uma amostra de pacientes com gliomas de baixo e alto grau antes da intervenção cirúrgica. MÉTODO: Os pacientes com glioma de baixo grau (G1, n=19) e alto grau (G2, n=8) foram avaliados quanto à memória, funções executivas, habilidades visuo-perceptivas e visuo-espaciais, nível intelectual e linguagem. RESULTADOS: Houve prejuízo significativo em G2 na memória episódica verbal e visual, funções executivas incluindo flexibilidade mental, fluência verbal nominal e categórica e velocidade de processamento de informações. G1 demonstrou apenas déficits específicos de evocação verbal e visual, flexibilidade mental e velocidade de processamento. CONCLUSÃO: Estes achados demonstraram níveis diferenciados de comprometimento nos domínios executivos e mnésticos de pacientes com gliomas de baixo e alto grau.

Development of an adapted version of the Boston Naming Test for Portuguese speakers / Desenvolvimento de uma versão adaptada do Boston Naming Test para a língua portuguesa

OBJECTIVE: To present the development of an adapted version of the Boston Naming Test for Portuguese speakers, and to investigate the effects of age, education and gender on both the original and the adapted Boston Naming Test in respect of Brazilian Portuguese speakers. METHOD: Eighty items, including the 60 original ones and 20 adapted items were administered to 739 healthy Brazilian subjects aged between 6 and 77 years who received 0 to 17 years of education. RESULTS: The coefficients of the General Linear Model estimation suggested that both age and education were statistically significant to predict total scores. In addition, score variances, justified by such predictors, were 41.20 percent in the original Boston Naming Test against 25.84 percent in the adapted Boston Naming Test. These results suggest that the scores from the original BNT are more dependent on age and education than those from the adapted Boston Naming Test. CONCLUSION: These findings demonstrated the suitability of the adapted Boston Naming Test version for the Brazilian population and described provisional norms for the original and adapted Boston Naming Test for Portuguese speakers.

OBJETIVO: Apresentar o desenvolvimento de uma versão adaptada do Boston Naming Test para a língua portuguesa e investigar os efeitos da idade, escolaridade e gênero nas versões original e adaptada do Boston Naming Test. MÉTODO: 80 itens foram administrados incluindo os 60 originais e 20 itens adaptados em 739 brasileiros saudáveis com idades entre 6 e 77 anos e escolaridade entre 0 e 17 anos. RESULTADOS: Os coeficientes de estimação do Modelo Linear Geral sugeriram que a idade e escolaridade eram preditores significativos do resultado total. Além disto, as variâncias dos resultados explicadas por estes preditores no Boston Naming Test original era de 41,20 por cento, enquanto que no adaptado era de 25,84 por cento. Estes achados sugerem que os resultados do Boston Naming Test original são mais dependentes de idade e escolaridade do que os do adaptado. CONCLUSÃO: Estes achados demonstram a adequação do Boston Naming Test adaptado para a população brasileira e descrevem normas provisionais da versão original e adaptada do Boston Naming Test para a língua portuguesa.