The Role of the Insular Cortex in Intertemporal Decision-Making

Progetto

The role of the insular cortex in intertemporal decision-making

Background. People often make decisions whose consequences are spread over time (e.g., Frederick et al., 2002), usually referred to as Intertemporal Choices (IC). For instance, one might choose if spending a smaller amount of money now, or saving it for the future. Commonly, people tend to prefer smaller gains immediately: the phenomenon for which they tend to assign a smaller value to future outcomes is referred to as Temporal Discounting (TD). During such decisions, emotions and drive states (e.g., hunger, drug craving) influence how to assign value to the options at the stake (Bechara and Damasio, 2005). TD is indeed elevated when people are hungry or tired, so that emotional responses promoting impatience are maximal (van Boven and Loewenstein, 2003). The insular cortex plays a critical role in emotion (e.g., Craig, 2009) and it is deemed to mediate the conscious representation of bodily states and the anticipation of the bodily consequences of emotional events (e.g., Damasio et al., 2000). By signalling the current needs of the body, such inputs – like the urge to obtain a reward soon, overwhelming attempts to implement far-sighted choices (e.g., Loewenstein, 1996) – influence the valuation of different goods. Imaging studies reported that insula activity modulates according to the time availability of rewards. For instance, its functional connectivity with regions involved in valuation and choice processes predicted decisions in a monetary IC task (Li et al., 2013). Moreover, insula was activated during difficult choices where the value of the sooner-smaller option is close to that of the larger-later option (Marco-Pallarés et al., 2010), and its activation has been found during choices of the larger-later option, even more in steeper discounters (Luo et al., 2012). However, insula activity has been associated with both delayed (Wittmann et al., 2007; Claus et al., 2011; Kayser et al., 2012) and immediate rewards (Tanaka et al., 2004; McClure et al., 2007; Wittmann et al., 2010), thus making conclusions about its specific role in IC difficult.

Aim of the study. Imaging studies can inform us only about correlations between brain regions and functions. To overcome these inferential limitations, we will use a lesional approach to elucidate the causal role of the insular cortex in IC.

Materials and methods

Participants. Patients with chronic lesion involving the insular cortex (N = 10; Insular patients), control patients with chronic lesion outside both insula and frontal cortex (N = 10; see Sellitto et al., 2010), and control healthy participants (N = 30), matched on age, gender, and education with patients, will be recruited from the Centre for studies and research in Cognitive Neuroscience, and the Department of Psychology of the University of Bologna, according to the Declaration of Helsinki (International Committee of Medical Journal Editors, 1991) and the Ethical Committee of the Department of Psychology, University of Bologna.

Lesion analysis. Patients will be selected on the basis of the most recent clinical CT or MRI. A neurologist expert in image analysis will trace the lesion on the T1-weighted template MRI scan from the Montreal Neurological Institute provided with the MRIcron software (Rorden and Brett, 2000). This scan is normalized to Talairach space and is a widely used template for normalization in functional brain imaging (e.g., Sellitto et al., 2010). Lesions’ location will be identified by loading the lesion drawings onto the Brodmann template provided with MRIcron and on the Automated Anatomical Labeling template (AAL, Tzourio-Mazoyer et al., 2002).

Experimental paradigm. We will use a modified version of the monetary TD task of Sellitto and colleagues (2010). In a computerized TD task, participants will choose between a hypothetical amount of reward that can be received sooner and a hypothetical amount of reward that can be received later. Two temporal conditions will be included (see also Kable and Glimcher, 2010): The Now and the Not-now conditions. In the Now condition, participants will make a series of choices between a smaller amount of money (in €) that can be received immediately (now), and 40 € that can be obtained after a variable delay. In the Not-now condition, choices will involve a smaller amount of money that can be received in 60 days, and 40 € that can be delivered after a variable delay larger than 60 days, while maintaining the same temporal gaps between earlier and later rewards as in the Now condition. Thus, in the Now condition participants will make five choices at each of six delays: 2, 14, 30, 90, 180, and 365 days, whereas in the Not-now condition the delays will be 62, 74, 90, 150, 240, and 425 days. Within each block of five choices, the amount of the sooner reward will be adjusted based on the participant’s previous choice, using a staircase procedure converging on the amount of the sooner reward that is equal, in subjective value, to the later reward. The first choice will be between a later amount of 40 € and a sooner amount of 20 €. If the sooner reward will be chosen, then the amount of the sooner reward will be decreased on the next trial; if the later reward will be chosen, then the amount of the sooner reward will be increased on the next trial. The first adjustment will be half of the difference between the sooner and the later reward, whereas for subsequent choices it will be half of the previous adjustment (Myerson et al., 2003). This procedure will be repeated until the subject will make five choices at one specific delay, after which the subject will begin a new series of choices at another delay/temporal condition. For each trial in a block, the sooner amount will represent the best guess as to the subjective value of the later reward. Therefore, the sooner amount that would be presented on the sixth trial of a delay block will be taken as the estimate of the subjective value of the later reward at that delay. Moreover, control conditions will be included. The blocks of choices pertaining to temporal and control conditions, as well as relatively to different delays, will be interspersed and randomized between participants.

Procedure. After completing the monetary TD task, participants will fill out, in a counterbalanced order, several self-report measures evaluating depression, impulsivity, and reward responsiveness, separately. Moreover, control tasks investigating the ability to estimate time and emotion/arousal and single option evaluation will be included.

Data analysis

Hyperbolic function. To compare the three groups, we will calculate, as main TD parameter, the k constant (Green and Myerson, 2004). The hyperbolic function SV = 1/(1+kD), where SV = subjective value (expressed as a fraction of the delayed amount), and D = delay between the two options (in days), will be fit to the data (as implemented in StatisticaStatsoft®), separately for temporal conditions. The smaller the value of k, the shallower the discounting function, the less participants will be inclined to choose smaller-sooner over larger-later rewards.

Voxel-based lesion-symptom mapping (VLSM).A VLSM analysis oriented at investigating the relation between brain damage and behavior on a voxel-by-voxel basis will be included. VLSM allows lesion-behavior associations to be tested without assigning patients to arbitrary groups. In this method, a behavioral measure is entered as the dependent variable, and the lesion status of each voxel (lesioned or not) is the independent variable. Then, for each voxel, statistical comparisons are made between performances of subjects with vs. without lesions affecting that voxel. The output is a statistical map indicating voxels associated with poor performance when lesioned (Bates et al. 2003). We will enter patients’ TD scores (k) in the Non-Parametric Mapping software (Rorden et al., 2007), separately for temporal conditions. The software compares performance of patients with vs. without damage at each voxel using the nonparametric Brunner-Munzel rank-order test (Brunner and Munzel, 2000).

Predictions and implications.If the insula is necessary to represent the emotional states associated with sooner and later rewards, Insular patients’ choices should be relatively devoid of emotion, and governed by a heuristic of quantity. We expected patients to be more willing to wait for larger-later outcomes than controls (shallower TD), along both temporal conditions. This tendency should be even more pronounced when a reward is available immediately, maximizing the involvement of emotion on decisions. Results from this study will help us to elucidate the role of insular cortex during IC in the context of the neural model proposed by our lab (Sellitto et al., 2010, 2011; Ciaramelli and di Pellegrino, 2011). Extant neuroscience evidence shows clearly that limbic structures – including the medial orbitofrontal cortex (mOFC) and the ventral striatum (VS) – and the dorsolateral prefrontal cortex (dlPFC) are core areas of the valuation and the control networks, respectively (e.g., Hare et al., 2009; Figner et al., 2010; Sellitto et al., 2010, 2011), thus governing IC. We propose that mOFC and the ventromedial prefrontal cortex activity is thought to track the subjective value of rewards over both short and long timescales, together with the posterior cingulate cortex and VS activity (e.g., McClure et al., 2004, 2007; Kable and Glimcher, 2010; Ballard and Knutson, 2009; Peters and Büchel, 2009). In this frame, we hypothesize that insular cortex could participate in providing low-level information about reward preference, remapping changes in bodily states generated by the amygdala (Winston et al., 2002), while mOFCcould consider and mediate these signals with those deriving from top-down cognitive control structures, like the dlPFC(e.g.,Christakou et al., 2011; Hare et al., 2009; Figner et al., 2010), encoding the value of rewards. This study has important clinical implication also, providing evidence about impatience during decision-making and being the potential starting point for new rehabilitation paradigms reducing urge and promoting abstinence (e.g., in compulsive gamblers and addicted or obese patients; e.g., Naqvi et al., 2007).

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Attività formativa dell’assegnista

Durante la durata dell'assegno di ricerca, l’assegnista svolgerà una serie di attività formative volte ad approfondire aspetti legati a:

a. tematiche teoriche relative alla neurobiologia delle scelte intertemporali e all’analisi del comportamento in pazienti cerebrolesi insulari, con relativo confronto con i dati del precedente lavoro pubblicato sul Journal of Neuroscience (Sellitto et al., 2010);

b. nuove metodologie relative all’analisi del comportamento di temporaldiscounting sulla base di nuovi modelli matematici e con l’utilizzo di nuovi parametri di discounting, avvalendosi della collaborazione del Dr JanPeters presso l’Università di Berkeley (California, USA); inoltre, nuove tecniche di programmazione e di analisi dei dati comportamentali (e.g., Psychtoolbox e Matlab);

c. scrittura dello studio previa discussione con il gruppo di ricerca, ed in collaborazione con la struttura “Spedali Civili” di Brescia, con invio a rivista internazionale di neuroscienze (Journal of Neuroscience), e divulgazione dello stesso a conferenze e congressi nazionali ed internazionali (e.g., Congresso annuale della Società Italiana di NeuroPsicologia, Society for Neuroscience,

d. periodo di visita presso il laboratorio del Professore Otto Karnath per l’approfondimento dell’utilizzo del software Mricron ( e partecipazione ad un corso di Statistical ParametricMapping per approfondire nuove tecniche di ricostruzione delle lesioni cerebrali (