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

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

Eliane C. Miotto^1*, Paulo R. Bazán², Alana X. Batista¹, Adriana B. Conforto¹, Eberval G. Figueiredo¹, Maria da Graça M. Martin², Isabella B. Avolio¹, Edson Amaro Jr.² and Manoel J. Teixeira¹

• ¹Department of Neurology, University of São Paulo, São Paulo, Brazil
• ²Institute of Radiology, LIM-44, University of São Paulo, São Paulo, Brazil

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.

Introduction

Cognitive impairment occurs in more than one third of patients with stroke and persists in many individuals for years, producing long-term disabilities (1, 2). Up to half of patients with cognitive deficits following stroke show significant impairment in episodic memory (3, 4). Episodic memory is a system implicated in the capacity to learn and recall past information or events (5). Cognitive rehabilitation is a traditional non-pharmacological treatment approach directed at the restoration of cognitive activity or the acquisition of efficient strategies to compensate for impaired cognitive function, particularly episodic memory (6, 7). In patients with memory impairments due to vascular and traumatic brain lesions, cognitive interventions have been recommended as a practice standard, including the use of internalized strategies (e.g., verbal association, visual imagery, etc.) and external memory compensation (e.g., cellphones, notebooks, diaries) (6–8). Recent studies demonstrated that patients with vascular lesions can benefit from different cognitive interventions including face-name training to remember people's names and repetition-lag memory training, developed to increase recollection as opposed to familiarity in recognition memory tasks (9, 10). There is also recent evidence of memory and attention improvement after computerized cognitive training and telehealth options for remote delivery of compensatory memory skills training after stroke (11, 12).

Semantic organization strategy training (SOST) is a cognitive intervention designed to recruit executive functions, semantic categorization, working memory, engaging regions of frontoparietal network, particularly in the left hemisphere due to verbal stimuli processing (13–15). This cognitive training (CT) intervention is based on the application of semantic organization strategy to word-lists in order to improve free verbal episodic memory recall and to enhance encoding by grouping words together that belong to the same category. Previous studies using SOST showed improvement in episodic memory in healthy adult individuals, patients with left frontal glioma excisions and mild cognitive impairment (14–16). Nevertheless, the underlying brain mechanisms related to cognitive interventions in patients with stroke remain largely unknown. In particular, no study has investigated, as yet, the effects of CT using SOST in patients with stroke in the left frontoparietal hemisphere.

Neuroimaging methods, particularly functional magnetic resonance imaging (fMRI), have been used to investigate the neural substrates underlying cerebral plasticity after cognitive training in a limited number of studies in patients with traumatic brain injury (17–20). In patients with vascular lesions or stroke, one study demonstrated changes in 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 in parallel to behavior improvements (9).

Another study found memory and executive function improvement and increased resting-state functional connectivity of the hippocampus with the frontal lobe (right inferior, right middle, left middle, left inferior, and left superior frontal gyrus) and the left parietal lobe in a small sample of patients with heterogeneous stroke lesions after computerized cognitive training using the RehaCom software package (21). The authors associated these findings with mechanisms of brain compensation and cognitive recovery in patients who received cognitive training.

The investigation of the impact of individual CT interventions, such as SOST, visual imagery, etc., outside the context of multi-domain cognitive and holistic rehabilitation programs is highly relevant to understand the effectiveness of each specific approach and its brain mechanisms to plan cognitive rehabilitation programs in a more effective way. Yet, no study has explored the behavioral effects and neural correlates of SOST intervention in patients with stroke, particularly, involving the left frontoparietal brain regions known to affect episodic memory encoding due to reduced strategy and efficient executive processes application (13–15). As described above, SOST intervention is thought to recruit left frontoparietal network regions due to its verbal stimuli word-list presentation and semantic strategy application in order to improve encoding and verbal episodic memory recall. Previous studies using SOST were carried in patients with left frontal tumors and MCI people (15, 16). Nevertheless, no investigation has, so far, been conducted in stroke patients, especially with lesions in those areas of the left frontoparietal network thought to be involved in this strategy. To pursue this investigation, a sample of healthy control participants would be necessary in order to investigate specific cerebral metabolic changes and extent of improvement in behavior in patients with left frontoparietal stroke lesions in comparison to what is seen healthy subjects.

Therefore, the aims of the current study were: (1) to investigate the cognitive performance changes, generalization effects and neural correlates of SOST intervention in patients with left frontoparietal stroke and healthy controls; and (2) to compare the behavioral and transfer or generalization effects and neural correlates of SOST with an active control psychoeducation intervention (PI). We hypothesized that all participants, particularly the stroke patients (SP), would benefit from SOST in comparison to the control intervention, and that different neuronal brain mechanisms would be involved in patients with ischemic stroke lesions in relation to healthy controls.