Dissociable Effects of Lesions to Orbitofrontal Cortex Subregions on Impulsive Choice in the Rat

“Coronal sections (60 m) were stained with cresyl violet and lesion locations were mapped onto standardized sections of the rat brain (Paxinos and Watson, 1998).”

“Preferential activation of mOFC is associated with choice of immediate primary or conditioned reinforcers relative to delayed ones (McClure et al., 2004, 2007) and correlates positively with individual differences in preference for smaller–immediate rewards on a delay-discounting task (Hariri et…”

“In primates, medial OFC (mOFC) has been associated with responding to, monitoring, or adjusting the incentive value of stimuli, whereas lateral OFC (lOFC) has been implicated in punishment or suppression of previously rewarded responses following contingency change (Iversen and Mishkin, 1970; Elliott et al., 2000; O’D…”

“OFC damage in humans leads to increased impulsivity, which may result from bias toward immediate rewards (Bechara et al., 2000; Berlin et al., 2004).”

“…nonhuman primates shows that caudal lOFC has dense interconnections with NAc core, ventral tegmental area (VTA), and BLA, whereas mOFC has dense reciprocal connections with the hippocampus and only weak connectivity with NAc core, VTA, and BLA (Morecraft et al., 1992; Carmichael and Price, 1995).”

“…and/or responses that lead to immediate feedback of reward (Elliott et al., 2000; O’Doherty et al., 2001) and bias stimulus-driven, behavioral responses toward immediate goals (McClure et al., 2004, 2007). mOFC damage could disrupt such bias, shifting responding toward larger– delayed options.”

“The orbitofrontal cortex (OFC) has been strongly implicated in reinforcement-guided decision making (Murray et al., 2007; Wallis, 2007; Doya, 2008).”

“Other researchers have hypothesized that mOFC may be better conceived as an integration site for subjective goal value signals (Kable and Glimcher, 2009), facilitating comparison of choice-options varying in parameters such as delay, magnitude, and probability.”

“Cardinal et al. (2001) observed a flattening of delaydiscounting curves across seven sessions following medial prefrontal cortex lesions that disappeared when delays were removed in alternating sessions.”

“…monitoring, or adjusting the incentive value of stimuli, whereas lateral OFC (lOFC) has been implicated in punishment or suppression of previously rewarded responses following contingency change (Iversen and Mishkin, 1970; Elliott et al., 2000; O’Doherty et al., 2001; Kringelbach and Rolls, 2004).”

“In primates, medial OFC (mOFC) has been associated with responding to, monitoring, or adjusting the incentive value of stimuli, whereas lateral OFC (lOFC) has been implicated in punishment or suppression of previously rewarded responses following contingency change (Iversen and Mishkin, 1970; Elliott et al., 2000; O’D…”

“However, other studies have reported that OFC lesions can shift preference toward the less-impulsive, delayed-reward alternative (Kheramin et al., 2002; Winstanley et al., 2004).”

“The orbitofrontal cortex (OFC) has been strongly implicated in reinforcement-guided decision making (Murray et al., 2007; Wallis, 2007; Doya, 2008).”

“Disruption of choice-behavior in OFC-lesioned animals after reversal is consistent with numerous studies (Chudasama and Robbins, 2003; McAlonan and Brown, 2003; Boulougouris et al., 2007).”

“These cells might maintain reward representation over delays and facilitate encoding of associative representations in downstream brain regions such as BLA and nucleus accumbens (NAc) (Schoenbaum et al., 2009).”

“, the smaller, moreimmediate option (Mobini et al., 2002; Rudebeck et al., 2006).”

“, 2004), correlates negatively with individual differences in relative preference for smaller–immediate rewards (Hariri et al., 2006), and correlates positively with the inclination to wait for larger– delayed rewards (Boettiger et al.”

“Disruption of choice-behavior in OFC-lesioned animals after reversal is consistent with numerous studies (Chudasama and Robbins, 2003; McAlonan and Brown, 2003; Boulougouris et al., 2007).”

“OFC damage in humans leads to increased impulsivity, which may result from bias toward immediate rewards (Bechara et al., 2000; Berlin et al., 2004).”

“…nonhuman primates shows that caudal lOFC has dense interconnections with NAc core, ventral tegmental area (VTA), and BLA, whereas mOFC has dense reciprocal connections with the hippocampus and only weak connectivity with NAc core, VTA, and BLA (Morecraft et al., 1992; Carmichael and Price, 1995).”

“, the smaller, moreimmediate option (Mobini et al., 2002; Rudebeck et al., 2006).”

“The apparatus and testing procedure have been described previously (Cardinal et al., 2000; Mar and Robbins, 2007).”

“Regardless, the similar directionality of lOFC- and wOFC-lesion effects suggests that lOFC is important for flexibility during reversal learning, consistent with other studies (Schoenbaum et al., 2003; Gourley et al., 2010).”

“…the extent of deferral of gratification (McClure et al., 2004), correlates negatively with individual differences in relative preference for smaller–immediate rewards (Hariri et al., 2006), and correlates positively with the inclination to wait for larger– delayed rewards (Boettiger et al., 2007).”

“Disruption of choice-behavior in OFC-lesioned animals after reversal is consistent with numerous studies (Chudasama and Robbins, 2003; McAlonan and Brown, 2003; Boulougouris et al., 2007).”

“Roesch et al. (2006) identified cells within lOFC, the activity of which rose until delayed-reward delivery.”

“The orbitofrontal cortex (OFC) has been strongly implicated in reinforcement-guided decision making (Murray et al., 2007; Wallis, 2007; Doya, 2008).”

“A recent study reported increased delay-discounting rates in patients with selective mOFC damage across three hypothetical intertemporal-choice tasks (Sellitto et al., 2010), in seeming contradiction to the present findings.”

“Recent studies in rodents also highlight the topographic separation of mOFC and lOFC projections to the striatum (Schilman et al., 2008).”

“Thus, lOFC may participate in circuitry that mediates cognitive control such as prospective planning or behavioral regulation in the context of stimulusindependent, long-term goals (Windmann et al., 2006).”

“Regardless, the similar directionality of lOFC- and wOFC-lesion effects suggests that lOFC is important for flexibility during reversal learning, consistent with other studies (Schoenbaum et al., 2003; Gourley et al., 2010).”

“However, given that their sequential choice-options varied in both delay and magnitude [quantitative models suggest such variations can potentially either suppress or promote delay-discounting (Kheramin et al., 2002)], a different choice strategy may have been adopted by patients with mOFC damage.”

“The apparatus and testing procedure have been described previously (Cardinal et al., 2000; Mar and Robbins, 2007).”

“, 2008; Young and Shapiro, 2009) and spatially cued operant responses (Boulougouris et al., 2007; Mar et al., 2011).”

“The basolateral amygdala and the hippocampus, as well as the lateral orbitofrontal cortex (lateral OFC) and medial OFC (mOFC) — but not the medial PFC 17 — have considerable modulatory effects on delay discounting 52–60 .”

“In the light of clinical evidence (6, 9), we asked whether we could restore the striatal inhibition by optogenetically altering lOFC input to the striatum.”