Tuesday, 18.05.2021

Peter R. Martin: Historical Vocabulary of Addiction




        The noun salience, according to the current electronic version of the Oxford English Dictionary (OED), is a combination of the adjective/noun salient and the suffix -ence.   The word salient is derived from Latin salientem, the present participle of salīre, meaning “to leap,” frequently assimilated wholly or partly to the French saillant.  The suffix -ence is from the French via the Latin -entia, forming abstract nouns, usually of quality, rarely of action, on participial stems in -ent- (e.g.,  audient-em hearing, audient-ia the process of hearing, audience).  An example of the first use of the noun salience in the English language, according to OED, was by James Henry Leigh Hunt (1784-1859), an English poet, journalist and literary critic, in his work The Seer; or, Common-Places Refreshed (1840): “The suddenness and salience of all that is lively, sprouting, and new.”  This is a rarely used meaning of salience: “The quality of leaping or springing up.” 

        A more recent and commonly used meaning of the word is: “A salient or projecting feature, part, or object.”  This use is exemplified by the following (Lofft 1837): “To people who would merely lounge along, side by side, these saliences are sorely annoying, they are abominable things.”  The most current meaning of salience is: “The fact, quality, or condition of being salient or projecting beyond the general outline or surface. Also of immaterial things.”  This use is found in the following quotation of Sir George Gilbert Scott  (1811-1878), a prolific English Gothic revival architect chiefly associated with the design, building and renovation of churches and cathedrals: “These subsidiary shafts may be …subordinated one to another, both in size and salience.” 

        The rather concrete meaning of salience as used in architecture was transformed into a more abstract sense as the word lept to a distant field, social psychology, from whence it evolved to become pivotal in the field of addiction: “The quality or fact of being more prominent in a person's awareness or in his memory of past experience.”  An example of this use of the word in psychology is found in the English translation of General Psychology from the Personalistic Standpoint by William Stern (1871-1938), a German psychologist and philosopher, known for the development of personalistic psychology which emphasizes the individual by examining measurable personality traits as well as the interaction of those traits to create the self (1938): “The different proportions of salience and embedding give the process and content of every experience its special character.” Contemporaniously, Gordon Willard Allport (1897-1967), an American psychologist often referred to as one of the founding figures of personality psychology, employed a very similar meaning in Personality: a Psychological Interpretation (1938):  “At other times... consciousness is embedded ...more deeply; there is less clearness, less salience. Salience represents an act of pointing, a directedness of the person toward something that at the moment has special significance for him.”  This last quotation accurately portrays the heightened role that is occupied by the pharmacologic actions of a drug of abuse or an aspect of the behavioral repertoire in the experiential framework of an individual who is suffering from an addictive disorder.

        Salience is the basis of preference and choice, a guiding feature of a behaving organism, free to engage with the world to seek fulfillment.   Attribution of salience can involve perceptual experiences in one or multiple sensory modalities, as exemplified by olfactory stimuli (Moskowitz and Gerbers 1974).  Salience and other elements of a sensory experience may be encoded in structural disparate brain regions.  For example, the functional separation of sensory and affective aspects of pain perception appears to extend to the memory of pain as well, such that distinct brain regions process sensory discriminative and affective components of pain (Albanese, Duerden, Rainville and Duncan 2007).  However, declaring that there is an emotional phenomenon termed “salience” that equates with positive biasing or attributions concerning experiential elements of the world that can guide behavior at a fundamental level is not fully satisfactory unless it can be measured.  Psychometric methods were initially all that were available to empirically evaluate topics of high, moderate or low importance (salience) in an individual’s life situation (Jackson, Manaugh, Wiens and Matarazzo 1971) – of course, declaration of the relative importance of an issue by a person has its own biases and sources of error but, nevertheless, can yield useful data.  Progressing from the psychometric approaches with only face validity, measures of the subjective bias of attention and other relevant brain functions can be more objectively measured using newer neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and event-related fMRI, which allows cognitive neuroscientists to examine brain processes related to salience using measures of neural activity (Driver and Frackowiak 2001).  For example, brain activation characteristics of the response to a sensory stimulus may be determined in terms of its magnitude and anatomic location.  As demonstrated by event-related fMRI, the emotional salience of a logical reasoning task can alter the region of the prefrontal cortex that was engaged in the cognitive process (Goel and Dolan 2003).  Cooper and Knutson (2008) used event-related fMRI to demonstrate that both valence (how positive or negative an emotion feels) (Olds and Milner 1954) and salience each partially accounts for nucleus accumbens (NAcc) activation during incentive processing.  This is a vital observation because of the pivotal role the NAcc in the reward pathways that are implicated in addiction (Wise 1987).

        Addiction constitutes a narrowing of the behavioral repertoire, limiting preference and choice because only a focused element of the world remains salient.  The behavioral changes accompanying addiction may occur, in part, because salience is an important modulator of learning (Beach and Shoenberger 1965), the fundamental brain mechanism underpinning addiction (Martin 2019).  The salience inherent in a specific experience can change depending on the stage of the addiction process.  For example, the salience of each cigarette smoked becomes significantly more powerful as one attempts to diminish smoking (Berecz 1984) and the salience of smoking-relevant cues in the environment can influence the magnitude of the desire to smoke (Payne, Schare, Levis and Colletti 1991).  The basis of the enhanced salience to smoking-related cues during smoking abstinence involves significant potentiation of neural responses in brain regions subserving visual sensory processing, attention and action planning in dorsomedial prefrontal cortex (McClernon, Kozink, Lutz and Rose 2009).  Drug and drug-associated stimuli may also activate memory circuits including the amygdala, hippocampus and dorsal striatum, all of which have dopamine-innervation and thus dopamine may influence motivational salience of the drug and associated stimuli (Volkow, Fowler, Wang and Goldstein 2002). Accordingly, withdrawal after repeated ethanol exposure produced several alterations in the physiological properties of ventral tegmental area (VTA) dopamine neurons, which could ultimately increase the ability of VTA neurons to produce burst firing and thus might contribute to reinitiation of addiction-related behaviors (Hopf, Martin, Chen et al. 2007).  Another way that salience and attentional biases towards cigarettes in addiction may be modified is through physiological states such as acute exercise which can reduce desire to smoke (Van Rensburg, Taylor and Hodgson 2009).

        The role of salience in shaping addictive behavior is demonstrated by the psychometric factors that may explain why one begins to use marijuana and continues its use, each potentially very different from the other (Lucas 1978).  This underlines that addiction is a process that changes the affected person – what is considered important to the individual (salient) is predictably transformed as a function of the time and quantity of drug use (Martin, Lovinger and Breese 1995).  Similarly, salience of food cues have been found to be associated with eating behaviors, expressed somewhat differently under circumstances of trying and not trying to lose weight, compatible with the notion that the phenomenon of salience is basic to addictive behaviors of all kinds, not simply drug use disorders (Collins 1978).  Importantly, corticosterone has been demonstrated to enhance the salience of saccharin, a non-caloric surrogate for motivated food intake (Bhatnagar, Bell, Liang et al. 2000).  As hypercorticalism from stress experienced during withdrawal occurs during each and every epoch of addiction to drugs or food, this excentuates the vicious cycle of repeated self-administration and perpetuates the likelihood of re-initiating use (Martin, Weinberg and Bealer 2007).  Moreover, it has been argued that allostatic changes alter salience making it less likely to self-administer enough of the drug to which an individual is addicted, thereby enhancing the pace of progression of the disorder (Koob and Le Moal 2006).

        Robinson and Berridge (1993) have interwoven salience into their Incentive-Sensitization Theory of Addiction, which has become pivotal for subsequent research in neurobiological underpinnings of addiction.  The theory posits:

        “…that addictive behavior is due largely to progressive and persistent neuroadaptations caused by repeated drug use.  It is, if you will, a ‘neuroadaptationist model’.  It is proposed that these drug-induced changes in the nervous system are manifest both neurochemically and behaviorally by the phenomenon of ‘sensitization’, which refers to a progressive increase in a drug effect with repeated treatment… it is proposed here that the defining characteristics of addiction (craving and relapse) are due directly to drug-induced changes in those functions normally subserved by a neural system that undergoes sensitization-related neuroadaptations.

        “The neural system that is rendered hypersensitive (‘sensitized’) to activating stimuli is hypothesized to mediate a specific psychological function involved in the process of incentive motivation: namely the attribution of incentive salience to the perception and mental representation of stimuli and actions.  This makes stimuli and their representations highly salient, attractive and ‘wanted.’  It is the activation of this neural system that results in the experience of ‘wanting,’ and transforms ordinary stimuli into incentive stimuli.

        “Sensitization of this neural system by drugs results in a pathological enhancement in the incentive salience that the nervous system attributes to the act of drug taking. The co-activation of associative learning directs the focus of this neurobehavioral system to specific targets that are associated with drugs and leads to an increasing pathological focus of incentive salience on drug-related stimuli. Thus, with repeated drug use the act of drug taking and drug-associated stimuli, gradually become more and more attractive.  Drug-associated stimuli become more and more able to control behavior, because the neural system that mediates ‘wanting’ becomes progressively sensitized. ‘Wanting’ evolves into obsessive craving and this is manifest behaviorally as compulsive drug seeking and drug taking. Therefore, by this view, drug craving and addictive behavior are due specifically to sensitization of incentive salience.

        “But ‘wanting’ is not ‘liking.’ The neural system responsible for ‘wanting’ incentives is proposed to be separable from those responsible for ‘liking’ incentives (i.e., for mediating pleasure) and repeated drug use only sensitizes the neural system responsible for ‘wanting.’  Because of this, addictive behavior is fundamentally a problem of sensitization-induced excessive ‘wanting’ alone. This is in contrast to ‘pleasure-seeking’ theories of addiction, which explicitly assume that the incentive motivational properties of drugs are due directly to their subjective pleasurable effects; i.e., their ability to produce positive affective states…The Incentive-Sensitization Theory is unique, however, because we propose the progressive increase in drug ‘wanting’ that characterizes addiction is not accompanied by an increase in the pleasure derived from drugs. Repeated drug use does not sensitize neural systems responsible for the subjective pleasurable effects of drugs, only those responsible for incentive salience – transforming ‘wanting’ into craving.”

        They conclude that “…the neuroadaptations underlying behavioral sensitization are long-lasting and in some cases they may be permanent…” and propose the hypothesis “that the neural substrate for incentive-sensitization (that is the neural system[s] that normally attributes salience to incentive stimuli and becomes sensitized by addictive drugs) is the mesotelencephalic dopamine system.”

        This theory has provided an important framework for evolution of the understanding of addiction, including the relevance of salience. From a purely behaviorist construct of drug self-administration based primarily on conditioning (Martin 2019), the theory makes place for emotional modulation of addictive behaviors.  In a sense, this is the first attempt to examine addiction, not simply as a function of the pharmacologic actions of a drug, but how these actions interact with individual characteristics and desires of the user.  This theory has led the way to elucidating the underpinning neural circuits (Zhang and Volkow 2019) and intracellular events within these circuits (Kalivas and Volkow 2005) that subserve the self-destructive and out-of-control behaviors that are characteristic of addiction.  Finally, Everitt and Robbins (2005) reconcile the interactions of conditioning with individual emotional attributions and weave in underpinning neuroplastic brain circuits that involve dopaminergic neurotransmission and thereby, explicate the process of addiction:

        “…as the endpoint of a series of transitions from initial drug use – when a drug is voluntarily taken because it has reinforcing, often hedonic, effects – through loss of control over this behavior, such that it becomes habitual and ultimately compulsive… these transitions depend on interactions between pavlovian and instrumental learning processes… the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.”  

        The role of salience should not be forgotten in this longitudinal process, as it is always there, even though it transforms and is transformed by the face of addiction at each stage of its development and progression.  



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December 31, 2020