Affective valence in the brain: modules or modes?

Abstract

How do brain systems evaluate the affective valence of a stimulus - that is, its quality of being good or bad? One possibility is that a neural subsystem, or 'module' (such as a subregion of the brain, a projection pathway, a neuronal population or an individual neuron), is permanently dedicated to mediate only one affective function, or at least only one specific valence - an idea that is termed here the 'affective modules' hypothesis. An alternative possibility is that a given neural module can exist in multiple neurobiological states that give it different affective functions - an idea termed here the 'affective modes' hypothesis. This suggests that the affective function or valence mediated by a neural module need not remain permanently stable but rather can change dynamically across different situations. An evaluation of evidence for the 'affective modules' versus 'affective modes' hypotheses may be useful for advancing understanding of the affective organization of limbic circuitry.

Fig. 1 |. The affective modules and affective modes hypotheses.

a | An affective modules hypothesis posits that a given neuron, neural system, projection or subregion reliably mediates only a single affective function. In the example shown here, which is based on some of the findings described in this article, a hypothesis of affective modules suggests that there are at least four affective modules within the nucleus accumbens shell. Each module is dedicated to mediating just one of four affective functions (the positive-valenced ‘liking’ and ‘wanting’ reactions and the negative-valenced ‘fear’ and ‘disgust’ reactions^,,,) and is activated by particular manipulations of the nucleus accumbens (for example, ‘liking’ enhancement is triggered by opioid stimulation in the rostrodorsal quadrant of the medial shell). b | An affective modes hypothesis that accounts for the same data would allow a given affective module (a given neuron, projection, neural system or subregion) to have more than one mode. For example, in the schematic example, module 1 (corresponding to a rostrodorsal site in the nucleus accumbens shell) can generate either pure ‘wanting’ (after dopamine receptor stimulation or AMPA receptor (AMPAR) blockade)^,, or ‘liking’ plus ‘wanting’ (in response to opioid receptor stimulation^,). Module 4 (corresponding to the caudal shell) can generate ‘wanting’ alone (after dopamine receptor or μ-opioid receptor stimulation)^,, ‘fear’ alone (after AMPA receptor blockade)^, or ‘disgust’ plus ‘fear’ (after GABA agonist microinjection)^,. However, a particular module may still have unique features that distinguish it from other modules (for example, only one of the modules illustrated has the capacity to enhance ‘liking’^, and only one has the capacity to generate ‘disgust’^,). A particular module also may retain a valence bias across modes (for example, module 1 has strong positive-valenced bias^,,, whereas module 4 has a negative-valenced bias^,) but still be capable of generating affective reactions of the opposite valence in particular modes (such as the switching between generation of ‘wanting’ and ‘fear’ by intermediate modules^,, or the ‘wanting’ enhancement obtained from negatively biased module 4 in the dopamine receptor or μ-opioid receptor stimulation modes^,,). GABAR, GABA receptor.

Fig. 2 |. Evidence for affective modules and affective modes in the nucleus accumbens.

a | A sagittal view of the medial shell of the rat nucleus accumbens shows the rostrodorsal ‘hedonic hot spot’, here revealed as the sites at which microinjections of μ, δ or κ-opioid receptor agonists all enhanced the hedonic impact of sucrose (blue circles; enhancement defined as 200–300% increases in taste-elicited orofacial ‘liking’ reactions)^,. The axis numerals mark stereotaxic coordinates relative to Bregma. Conversely, in a caudal ‘hedonic cold spot’, the same opioid microinjections suppressed ‘liking’ reactions by ~50% (red circles). The bottom section shows the location of a shared opioid hot spot for hedonic enhancement and shared cold spot for hedonic suppression. b | A sagittal view of the rat nucleus accumbens shows a bivalent rostrocaudal gradient pattern of affective modules in the medial shell, revealed by microinjections of a glutamate AMPA receptor antagonist. Dark blue circles indicate microinjection sites that produced selective increases in appetitive motivation to eat food (similar results were shown in REF.). Yellow circles show microinjection sites that enhanced both mixed appetitive and defensive behaviours, with these behaviours typically alternating in the same rat in the hour after microinjection. Red circles show microinjection sites that enhanced only actively defensive or ‘fearful’ behaviours. This study revealed shifts of the valence function of many microinjection sites driven by changes in environmental ambience. When rats were tested in a quiet, dark home environment, microinjection at most sites enhanced only appetitive behaviour. In a standard laboratory environment with moderate illumination and background sound levels, the nucleus shell was evenly divided between rostral appetitive, central mixed and caudal defensive zones. In a stressful highly illuminated and noisy laboratory environment, defensive and mixed zones expanded whereas the appetitive zone shrank to only the far-anterior edge. C, caudal; D, dorsal; R, rostral; V, ventral. Part a republished with permission of the Society for Neuroscience, from Opioid hedonic hotspot in nucleus accumbens shell: Mu, delta, and kappa maps for enhancement of sweetness “liking” and “wanting”. Castro, D. C. & Berridge, K. C. 34(12), 2014; permission conveyed through Copyright Clearance Center, Inc. (REF.). Part b is adapted from REF., Springer Nature Limited.

Fig. 3 |. Evidence for affective modules and affective modes in the central amygdala.

a | An anatomical depiction of sites within the central amygdala (CeA) at which optogenetic neuronal stimulation magnified and narrowly focused appetitive motivation to seek and consume a cocaine reward that was paired with the stimulation, compared with seeking alternative cocaine without amygdala stimulation (blue circles indicate increased appetitive motivation). Control sites in the basolateral amygdala (BLA) are also shown, at which optogenetic stimulation failed to enhance appetitive motivation (white circles indicate no change and yellow and orange circles indicate relative avoidance of optogenetic-paired cocaine). Sites throughout most of the CeA supported amplification of appetitive motivation in both the lateral (CeL) and medial (CeM) subdivisions of this nucleus. b | A synthesis of affective modular hypotheses that view most CeA modules as negative-valenced modules that permanently mediate ‘fear’ or defensive reactions while allowing some other CeA modules to mediate positive-valenced motivations such as appetitive ‘wanting’^,–. This figure shows negative-valence dominance in the CeA, in accordance with popular views, but some modular hypotheses might posit an equal balance of positive and negative modules. c | An affective modes hypothesis allows each CeA neuronal module to have more than one mode and to mediate either positive valence or negative valence. According to this hypothesis, a particular CeA module may have a valence bias (for example, here modules at the left have negative-valence biases whereas modules at the right have positive-valence biases), but any given module is capable of switching to the opposite valence in at least one mode. Three potential modes are shown in rows at the bottom, consistent with data suggesting that some, or conceivably even all, CeA modules may be capable of mediating either appetitive or defensive motivations^,,. The optogenetic appetitive CeA mode described in part a corresponds to the third mode in the bottom row. A mixed compromise hypothesis could add one or two pure-valence modules if single-valence neural modules are ever proved to exist in the amygdala (not shown). Part a is adapted with permission from REF., Society for Neuroscience.