Neural Control of Vascular Reactions: Impact of Emotion and Attention Hadas Okon-Singer, Jan Mehnert, Jana Hoyer, Lydia Hellrung, Herma Lina Schaare, Juergen Dukart and Arno Villringer Journal of Neuroscience 19 March 2014, 34 (12) 4251-4259; DOI: https://doi.org/10.1523/JNEUROSCI.0747-13.2014 Abstract This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure（CareTaker 、Emperical Technologies）;. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance. Introduction Threatening stimuli prototypically facilitate adaptive motor behavior and activate the autonomic nervous system, affecting heart rate and blood pressure (Lang et al., 2000). These vascular responses can aggravate when the threatening situation develops into stress for the organism. It has been shown that, among healthy subjects, those with higher blood pressure responses are more likely to subsequently develop hypertension (Matthews et al., 2004). It is therefore highly relevant to identify neural mechanisms for the vascular response and potential ways to modulate it. Studies on the neural underpinnings of vascular response to stress identified brain areas known to be associated with emotion processing, including the amygdala, insula, and cingulate (Gianaros and Sheu, 2009). These pioneer studies used intermittent blood pressure measurements between functional neuroimaging and were therefore limited to longer-lasting “stress periods.” Recent technical developments (Gray et al., 2009), however, on which we build here, allow for simultaneous recording of blood pressure during fMRI to match neural activity associated with brief (threatening) events closely to blood pressure changes. Regarding potential ways to modulate emotion-related autonomic responses, a crucial question concerns the degree to which reactions to emotional stimuli are affected by cognitive mechanisms. A debate exists on whether processing of emotional items depends on allocation of sufficient attention to them (see Pessoa et al., 2002 and Evans et al., 2011 for similar effects on attention bias to drug-related cues in drug-addicts). Recent models propose that projections from frontoparietal regions to amygdala modulate reactions to emotional stimuli (cf. Pessoa, 2009, Pourtois et al., 2013). Conversely, it has been suggested that although attention influences emotion processing, it may not affect neural activation related to defensive motor responses (Pichon et al., 2012). If the latter were coupled to autonomic responses, this would mean that (action-related) vascular responses to emotional stimuli could occur independently of attention to them. Motivated by these considerations, the aims of this study were to identify neural regions involved in blood pressure responses to emotional stimuli and to elucidate whether and how attention modulates these neural processes and the associated vascular response. Our study builds on an affective perceptual load task that we previously established to assess the impact of attention on emotion processing (Okon-Singer et al., 2007). Participants discriminate a target letter among few (low load) or many (high load) distractor letters, whereas they are asked to ignore simultaneously presented distractor pictures that are emotionally negative or neutral. Using this paradigm, we investigated whether attention affects behavioral, neural, and vascular reactions to irrelevant emotional distractors in healthy individuals. In the low-load condition, negative pictures were hypothesized to deteriorate task performance, to activate regions implicated in emotion processing (amygdala, anterior insula, orbitofrontal cortex, visual areas), and to transiently decrease blood pressure (Minati et al., 2009, Dan-Glauser and Gross, 2011). In high load (reduced attention) these reactions were hypothesized to be attenuated. Finally, we expected activations related to enhanced perceptual load in frontoparietal and primary visual regions. Materials and Methods Subjects Twenty-four healthy subjects (11 females; mean age = 24.75 ± 2.49 years) without any history of neurological, psychiatric, vascular, or cardiologic diseases volunteered to participate in the study in return for payment. The study was approved by the local ethics committee and all subjects gave informed consent before the experiment. All subjects were right handed according to the Edinburgh Handedness Inventory (Oldfield, 1971) and all fell in the normal range of anxiety and stress as assessed by the German version of the Spielberger State-Trait Anxiety Inventory (Laux et al., 1981) and the Trier Inventory of Chronic Stress (Schulz and Schlotz, 1999), respectively. Due to technical problems, the behavioral data of five subjects was not recorded, so the behavioral analysis is based on 19 subjects (11 females). In addition, after technical challenges involved in recording blood pressure continuously and noninvasively inside the MRI scanner, the blood pressure measurement of eight of the initial 24 subjects contained >40% signal dropout (caused by slight movements of the subjects resulting in signal loss and low-pressured attachment of blood pressure sensors; see further details regarding data preprocessing in the “Blood pressure pre-processing” section). Therefore, we performed two types of analyses (see details in “Data analysis” below): (1) analysis of the fMRI data, without correlating them to the blood pressure measures, was performed to examine the neural correlates of the interaction between attention and emotion and was based on fMRI data acquired from all 24 participants (the fMRI data were not affected by the signal dropouts); and (2) analyses correlating the fMRI data with the blood pressure measurements, which had to be conducted based on 16 participants (nine females) due to the signal dropouts and unreliable blood pressure data from eight subjects and include both a parametric modulation analysis and an analysis with a continuous blood pressure regressor (see details in the “Correlation with blood pressure: parametric modulation analysis” and the “Correlation with continuous blood pressure” sections).