Gorka Navarrete

Universidad Adolfo Ibáñez · School of Psychology

Neurodegenerative conditions, which are characterized by prolonged pre-symptomatic stages and typically lead to dementia, represent a burden for public health systems and societies worldwide. This is especially true in middle- and middle-high-income countries. Promisingly, embodied and situated cognition approaches indicate that context-sensitive emotional and linguistic tasks can have important translational applications to favor detailed characterization and timely diagnosis of human neurodegenerative diseases at early stages (HNDES). To contribute to this critical endeavor, this project relies on context-sensitive models of emotion and language to assess disease-specific markers of highly prevalent HNDES through a combination of state-of-the-art brain techniques and embodied/situated behavioral paradigms. Most previous reports in the field have used imaging or electromagnetic techniques and are provided correlational evidence, as they failed to reveal causal effects between key brain areas and behavioral performance. To circumvent this limitation, here we will adopt the lesion model approach, which provides direct links between such dimensions. Our focus will be on the assessment of early stage behavioral variant frontotemporal dementia (bvFTD) and Parkinson’s disease (PD). These conditions represent a multilevel lesion (atrophy) model which offers unique opportunities to understand how areas specifically targeted by each disease contribute to embodied and situated cognitive processes. BvFTD constitutes a critical model to test deficits in contextual appraisal of emotions related to fronto-insulo-temporal atrophy. For its own part, PD affords a proxy to evaluate action language deficits and their relation with motor damage (basal ganglia and frontostriatal loops). Moreover, we will also assess a third clinical group, comprised of Alzheimer’s disease (AD) patients, as this condition offers a contrastive lesion model with damage to regions not classically associated with our two target domains. As shown in previous reports of our team, the combined study of bvFTD, PD, and AD may unveil specific and unspecific brain regions subserving contextual modulations of emotion and language. Throughout the project, and based on our previous multi-lesion studies, we will recruit 100 participants (25 subjects per clinical group and 25 healthy controls). We pursue several specific goals. First, we will evaluate the role of contextual variables in emotional and action-language domains in each HNDES subtype. On the one hand, to assess specific contextual modulations of emotional deficits in bvFTD relative to the other groups, we will administer two tasks: the interoceptive modulation of emotional appraisal task (IMEAT) and the emotional context-target association task (ECTAT). The IMEAT evaluates the impact of interoceptive training (based on heartbeat detection paradigms) on emotional recognition. We will measure reaction times and accuracy in emotion recognition (before and after interoceptive training) as well as high-density electrophysiological (hd-EEG) correlates –namely, connectivity patterns as well as modulations of the heart-evoked potential (HEP) during interoceptive tasks and other event-related potentials during emotional processing. The ECTAT taps into implicit and explicit context-target associations of facial expressions and emotional body language. In this task we will measure reaction times, emotion recognition accuracy, and hd-EEG correlates (connectivity and modulations of the N170 and HEP). On the other hand, to evaluate the specificity of action-language impairments in PD relative to the other groups, we will use two relevant tasks: the naturalistic text comprehension/production task (NTCPT) and the picture-based action-verb priming task (AVPT). Through the NTCPT we will examine the comprehension and production of action-laden texts in ecological modalities. We will focus on differential lexico-semantic variables and, during the comprehension phase, we will assess brain connectivity patterns (derived from hd-EEG data) and the HEP modulations. Then, using the AVPT, we will explore context-target priming of action- vs. object-related concepts. We will measure reaction times, accuracy, and hd-EEG correlates sensitive to semantic variables. Moreover, for both emotion and language tasks, we will analyze associations between differential behavioral profiles in each group and three neuroimaging measures: structural atrophy (via voxel-based morphometry), structural connectivity (through diffusion tensor imaging), and functional connectivity (based on functional magnetic resonance imaging). Finally, we will use complementary statistical methods to characterize, classify, and analyze the HNDES subtypes by combining behavioral profiles and their neurocognitive correlates with the best predictors of clinical description and behavioral outcome. Through this multidimensional approach, this project will substantially contribute to our understanding of the neurocognitive bases of contextual effects in social-emotional and linguistic mechanisms which lie at the core of human interactions. To this end, we will produce multiple high-impact publications and promote actions to raise awareness of HNDES in the community, including meetings and talks for scientists, medical professionals, students, patients, and patient relatives. Crucially, the project will be supported by both an international advisory board of leading researchers in their respective fields and an active international collaboration network involving multi-center protocols in the USA, the UK, Germany, Australia, Argentina, Chile, and Colombia. In sum, the state-of-the-art investigation proposed herein will help us understand how context influences behavior, thus paving the way for translational interventions capable of ameliorating the patients’ everyday functioning.