Cocaine Polydrug Use and its Impact on Intentional Harm Recognition: A High-Density EEG Study

doi:10.21203/rs.3.rs-3974162/v1

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Cocaine Polydrug Use and its Impact on Intentional Harm Recognition: A High-Density EEG Study

https://doi.org/10.21203/rs.3.rs-3974162/v1

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Cocaine and stimulant consumption constitute a significant problem worldwide related to impaired social skills. The link between illegal substance abuse and social cognition is not well understood. Intentional harm recognition is a social cognitive capability referring to the ability to determine whether a harmful action performed by another person is deliberate or accidental. The present study examined self-reported, behavioral, and neural responses associated with intentional harm in n=19 cocaine polydrug users (COC) and n=19 healthy controls (HC). Using high-density electroencephalography (hdEEG), brain activity was measured during an intentional inference task (IIT), which assesses fast intention recognition regarding deliberate or unintentional harm to people and objects. Behaviourally, COC exhibited slower RT than HC. ERP analysis showed late frontal differences associated with attributing intentional harm in HC but not COC. Finally, these findings may potentially indicate a shift towards emotional over-involvement and away from rational cognitive assessment of social information. The present results provide a new perspective on social-cognitive skills among cocaine polydrug users, suggesting that work in training socio-emotional regulation may be of clinical benefit.

Substance use disorder

Social Cognition

Intentional harm

Intentional inference task (IIT)

hdEEG

Estimates suggest that 296 million people use drugs, which represents an increase of 23% over ten years. 39.5 million individuals suffering from a substance use disorder (SUD), this represents an increase of 45% over ten years annually (UNODC, 2017). Twenty-two million people have problems with cocaine, and these numbers are disproportionately represented by cocaine consumption among countries in Central and South America. Within this region, the annual prevalence of cocaine use is highest among Chile (1.1%), Argentina, Uruguay (1.6%), and Costa Rica (1.2%) (UNODC, 2017).

In addition to the burden of disease, substance use has important implications for broader indicators of well-being. While 9.3% of the general population in Brazil has experienced some form of violence, exposure to violence is more than twice that (19.7%) among cocaine users (Abdalla et al., 2018). The likelihood of being involved in violent crimes increases by a factor of 4 among cocaine users (Abdalla et al., 2018). While causal links cannot be ascertained from these statistics, it is worrying that individuals who use cocaine are at greater risk of being the victims and perpetrators of violent crimes. Given the evidence that certain drugs lead to Disinhibition (De Wit, 2009; Garavan & Hester, 2007), cocaine use may be directly linked to violent crime (Markowitz, 2005; Parker & Auerhahn, 1998). However, it is also possible that socio-economic status accounts for the link between substance use and violence (Vermeiren et al., 2003).

The same factors underpinning exposure to violence and drug abuse among those of low socioeconomic status (SES) may also be related to other deficits in daily life functioning. People with substance use disorder (SUD) are known to be linked to deficits in socio-affective and cognitive function (Ersche et al., 2011; Potvin et al., 2014; Preller, Hulka et al., 2014; Verdejo-Garcia, 2014). These deficits may be the precipitant to or consequence of regular drug use. The effects of frequent drug use, such as blunted reward and general Disinhibition, may render specific individuals more likely to experiment with certain drugs. Such vulnerability is expected to be more pronounced among individuals from lower socio-economic backgrounds (Redonnet et al., 2012). Lack of rewarding social encounters, along with insufficient social support, may impact initial and continued drug use (Daniel et al., 2009; Galea & Vlahov, 2002). Lack of social support and adaptive coping strategies, along with easy access to drugs, is likely to promote and maintain use among individuals from lower socio-economic strata (Little & Steinberg, 2006). Continued usage is expected to dynamically interact with vulnerability factors, creating further social and functional impairments.

Intentional harm is a critical component of effective social interaction, which implies understanding the goals, intentions, and mindset of others (i.e., Theory of Mind) (Decety et al., 2012). Misunderstanding the choices of others is likely to lead to miscommunication, arguments, and unpleasant interpersonal experiences. Specifically, intention recognition or inference is critical to Empathy and moral decision-making processes (Frith & Frith, 2012; Van Overwalle, 2009). Intention recognition refers primarily to the ability to cognitively determine if an action performed by another person is accidental or voluntary (Baez et al., 2016; Escobar et al., 2014a). Intentional harm detection involves early and late brain responses involving the amygdala and frontotemporal coupling (Hesse et al., 2016). Intentional harm detection requires integrating complex processes such as emotion and cognition and is moderated by individual psychological traits (Blakemore & Decety, 2001; Castiello, 2003; Heberlein, 2008). Intention recognition has been studied in the context of moral decision research (Decety & Cacioppo, 2012a), the development of social abilities in young people (Escobar et al., 2014b), and dementia (Baez et al., 2016). Despite impaired socio-cognitive function among stimulant drug users (Quednow, 2017; Volkow et al., 2011) and the potentially critical role that lack of intentional harm detection may play in facilitating interpersonal deficits and heightened violence exposure among drug-affected individuals, no one has investigated intentional harm detection in a sample of cocaine abusers. More importantly, such work has not been conducted while controlling SES (an essential potential confound).

The Intentional Inference Task (IIT) (Escobar et al., 2014a) assesses fast intention inference regarding actions involving harm to others (intentional vs. unintentional) with different targets (Object vs. Person) (See Fig. 1). The IIT task primarily studied moral behavior and its brain correlates in healthy people (Decety & Cacioppo, 2012b). Also, it has been used to study the effects of early social deprivation on the intention inference capabilities and the extent of deficits due to frontotemporal dementia and frontal lesions (Baez, Couto et al., 2014). While the IIT is typically used to study moral decisions, it is also ideally designed to differentiate how individuals perceive the perpetration of violent behavior against objects and individuals, intentionally and unintentionally (Decety et al., 2009). Given the links mentioned above between substance use (cocaine use in particular) and violent behavior, as well as known deficits in socio-cognitive processes among individuals with SUD (Quednow, 2017; Volkow et al., 2011), we employed the IIT to explore the potential influence of chronic cocaine use, as well as numerous psychological factors (i.e., empathy, sensation-seeking, executive function) on intention inference. Alterations to the brain's early and late temporal dynamics have been observed among event-related potentials (ERPs) during this task (Decety & Cacioppo, 2012b). Different amplitude modulations have been apparent for intentional vs unintentional conditions, likely reflecting functions such as emotion processing, arousal activation, and cognitive evaluation. The most pronounced effects of this task have been reported in frontal electrodes (Escobar et al., 2014a).

For this study, we aimed to examine the neural signatures (i.e., event-related potential - ERP) linked to behavior during the IIT. Given the number of factors influencing socio-cognitive processes, especially among individuals with varied socio-economic backgrounds, it is critical to control for potential confounds. In the present study, Cocaine polydrug users (COC) were compared to a demographically and socioeconomically matched healthy control group (HC). To ascertain possible influences of early childhood upbringing, we assessed individual differences in parental bonding (See supplementary table 1). We also collected measures of Empathy, sensation-seeking, and executive function; these variables may constitute confounds and indirect ways individuals with SUD exhibit socio-cognitive impairments.

Given that attention is affected in periods of abstinence and related to behavioral performance (Bolla et al., 2000; Colzato et al., 2009), Click or tap here to enter text. We predicted that COC would be slower and less accurate than HC in the intentional inference task. Also, we predicted that COC would exhibit worse performance than HC for executive functions, consistent with impairments in general executive function (Hagen et al., 2016). We also predicted group differences in Empathy and sensation seeking (COCs exhibiting less Empathy and more sense-seeking than HCs). At the neural level, we expected a difference in HC ERP modulation relative to COC in pre-defined frontal regions of interest (ROI) (Escobar et al., 2014b). Specifically, we predicted that COC would exhibit less amplitude modulation than HC, corresponding to less emotional arousal (Imbir et al., 2015). We expect group differences to be significantly pronounced for intentional vs unintentional condition comparisons.

Participants

Our sample comprised two groups, COC, and Healthy controls HC. At the time of evaluation, the COC group was engaged in outpatient treatment for substance use problems at the National Service for the Prevention and Rehabilitation of Drug and Alcohol Consumption (SENDA). Participants were given the World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test (WHO-ASSIST; (Group, 2002) to assess the amount and extent of use of 10 different drugs. The HC group was matched for age, sex, and educational level (See Table 1 in supplementary data for complete academic-level information). A neuropsychologist evaluated all participants; participants with any history of medical conditions (other than substance use problems in COC) were excluded. All participants provided written informed consent following the Declaration of Helsinki.

Table 1

Abuse dependence by substance.
Substance	Abuse		Dependence
	HC % (n)	COC % (n)	HC % (n)	COC % (n)
Tobacco	5.26 (1)	68.42 (13)	31.57 (6)	94.73 (18)
Alcohol	42.10 (8)	84.21 (16)	0.00 (0)	73.68 (14)
Marijuana	0.00 (0)	94.73 (18)	0.00 (0)	73.68 (14)
Cocaine	0.00 (0)	100 (19)	0.00 (0)	100 (19)
Amphetamines	0.00 (0)	57.89 (11)	0.00 (0)	15.78 (3)
Sedatives	0.00 (0)	36.84 (7)	0.00 (0)	5.26 (1)
Opiates	0.00 (0)	5.26 (1)	0.00 (0)	0.00 (0)
COC = Cocaine polydrug users; HC = Healthy Group; % (n) = Percentage and the number of the sample who have the risk for abuse and dependence related to a specific substance.

Neuropsychology and self-reported measures.

Drug use, cognitive and socio-emotional assessment.

Participants performed several tasks and self-report measures to assess general cognitive processes (executive functions), socio-emotional skills (Empathy; sensation seeking), and self-reported drug patterns. Performance on these measures was compared between groups. Finally, a correlation test was performed between ERP amplitudes and the empathic self-report measure.

Drug use.

World Health Organization – Alcohol, Smoking, and Substance Involvement Screening Test (WHO-ASSIST): The WHO-ASSIST (v3.0) assesses lifetime substance use and use in the past three months in addition to providing estimates of risk for future substance use problems and the likelihood of substance use disorder diagnoses (i.e., abuse and dependence). Version 3.0, from an adapted and validated test used in Chile (Soto-Brandt et al., 2014), covers ten substances: tobacco, alcohol, cannabis, cocaine (including base paste and cocaine hydrochloride), amphetamines, inhalants, sedatives, hallucinogens, opiates and other drugs. The final scores for each substance are classified into three levels of risk (low, intermediate, and high) (Group, 2002).

Cognitive skills.

INECO Frontal Screening

The INECO Frontal Screening (IFS) is a relatively quick way to assess executive functions and has been mainly used as a screening tool. This battery has shown good internal consistency, high reliability, and concurrent validity (Torralva et al., 2010). The tasks included in the IFS are Luria motor series (3 points), Conflicting instructions (3 points), Go-no goes (3 points), Calendar months backward (2 points), Backwards digit span (6 points), Modified Corsi tapping test (4 points), Proverb interpretation (3 points) and Modified Hayling Test (6 points). The IFS has a maximum possible score of 30 points. High scores indicate the preservation of executive functions, with a cut point of 18 points for the Chilean version showing a typical performance in global executive functions for this population (Ihnen et al., 2013).

Socio-emotional skills.

Interpersonal Reactivity Index

The interpersonal reactivity index (IRI) was developed to assess four dimensions of empathy (Empathetic concern, perspective-taking, personal distress, and fantasy). Each subscale contains seven items. The Empathic Concern subscale assesses emotional Empathy or feelings of compassion for others in pain. The Perspective Taking subscale considers cognitive Empathy, or the tendency to see the world from others' viewpoints. The Personal Distress subscale assesses self-focused responses to others' suffering. The Fantasy subscale assesses Empathy for fictional characters. The first three subscales have exhibited relationships to more adaptative interpersonal (e.g., prosocial behavior) and intrapersonal (e.g., mental well-being) functioning (Davis, 1983a; Fernández et al., 2011).

Sensation Seeking Scale: The Sensation Seeking Scale (SSS) was developed to provide a trait measure of sensation-seeking. Form V of this scale (SSS-V) is a forced-choice questionnaire that yields four subscale scores: a) adventure seeking (TAS), b) experience seeking (ES), c) disinhibition (DIS), and boredom susceptibility (BS). The SSS-V scale contains 40 items, with ten items for each subscale (Schmidt et al., 2017).

Behavioral task and procedure.

Intention inference task (IIT)

Electroencephalography (EEG; see below for details) was recorded while participants completed a modified version of the Intention Inference Task (Baez, Manes, et al., 2014; Decety & Cacioppo, 2012a; Escobar et al., 2014a). The IIT assesses fast intention inference regarding actions involving harm to others (intentional vs. unintentional) with different targets (object vs. Person) (See Fig. 1). Participants were asked to evaluate whether the actions they saw were intentional or unintentional. In this study, participants were presented with a series of three-frame videos (total 300 ms, 100 ms each frame) on a computer screen. The first frame (T1) shows the start of the action. The second frame (T2) presented either intentional or unintentional harm images. The third frame (T3) showed the result of the action. The trials began with a fixation cross presented for 800 ms, and the inter-trial interval was fixed to 500 ms. During the experiment, accuracy and reaction times were recorded. There were 184 trials (46 per condition: Person Intentional, Person Unintentional, Object Intentional, and Object Unintentional).

Brain recording.

EEG recordings and pre-processing

EEG data were recorded with 128-channel HydroCel Sensors using a GES300 Electrical Geodesic amplifier at a sampling rate of 500 Hz. The vertex was used as the reference during the recording, but signals were re-referenced offline to the mastoids. ERP analyses were conducted using MATLAB R2017b, EEGLAB 13.15.4b, and ERPLAB 5.0.0. The data was digitally filtered offline from 0.5 Hz to 30 Hz and downsampled to 250 Hz to remove unwanted frequency components. Also, Trials that contained voltage fluctuations exceeding ± 200 µV were rejected. Eye movement, other artifacts, and trial rejection were removed from further analysis using visual inspection and Independent Component Analysis (ICA).

Continuous EEG data was segmented using a temporal window that began 200 ms before the onset of the stimulus and concluded 800 ms after the offset of the stimulus.

Data analysis.

Neuropsychological and self-reported measures

Independent samples t-tests were used to compare cognitive skills and psychological traits between groups.

Behavioral performance: Repeated measure ANOVAs and Tukey HSD post-hoc comparisons were performed to analyze behavioral IIT data (i.e., reaction time (RT) and accuracy (ACC)). Analysis was conducted in Jamovi (Jamovi project (2018). Jamovi (Version 0.9) [Computer Software]. Retrieved from https://www.jamovi.org).

ERP analysis: Repeated measure ANOVAs and Tukey HSD post-hoc comparisons were performed to analyze ERP IIT data. We used a previously defined group of electrodes for ROI analyses, comprising a frontal, central, and posterior zone (FZ, CZ, and PZ, respectively). Social cognition studies have previously reported time-series analysis in these representative ROIs. Past work has focused on three time windows for stimulus processing the IIT (early – middle – late). (Decety & Cacioppo, 2012b; Escobar et al., 2014b).

Sample characteristics.

Participants

The sample consisted of 19 COC (7 female, 12 males; mean age 32.2, SD = 8.7) and 19 HC (7 female, 12 males; mean age 31.8, SD = 8.0) individuals. (See Table 1 in supplementary data for complete educational level information).

Self-reported and neuropsychological results.

Substance abuse

Consistent with group selection, (COC) showed a 100% risk for abuse and 100% risk for dependence relative to 15.7% and 0%, respectively, in HC. Among COC, cocaine represents 100% of the risk for abuse and dependence, followed by marijuana and alcohol (see Table 1). Lifetime substance use was comparable across groups for alcohol, but only COC showed use of other drugs (see Table 2). Only COC exhibited drug-related impairment in daily life (see Table 3. For more information, see supplementary data in Table 2–4).

Table 2

Lifetime substance use by group.
Substance	COC % (n)	HC % (n)
Tobacco	94.73 (18)	31.57 (6)
Alcoholic drinks	84.21 (16)	84.21 (16)
Marijuana	89.47 (17)	0.00 (0)
Cocaine	100 (19)	0.00 (0)
Amphetamines or other stimulants	52.63 (10)	0.00 (0)
Inhalants	36.84 (7)	0.00 (0)
Tranquilizers or sleeping pills	31.57 (6)	0.00 (0)
Hallucinogens	21.05 (4)	0.00 (0)
Opiates	5.26 (1)	0.00 (0)
Others-specify	5.26 (1)	0.00 (0)
COC = Cocaine polydrug users; HC = Healthy Group; % (n) = Percentage and the number of the sample that reported the use of some substance in the list.

Table 3

Health, social, legal, or financial problems related to substance use.
Substance	COC % (n)	HC % (n)
Tobacco	52.63 (10)	5.26 (1)
Alcoholic drinks	68.42 (13)	0.00 (0)
Marijuana	63.15 (12)	0.00 (0)
Cocaine	84.21 (16)	0.00 (0)
Amphetamines or other stimulants	15.78 (3)	0.00 (0)
Inhalants	10.52 (2)	0.00 (0)
Tranquilizers or sleeping pills	0.00 (0)	0.00 (0)
Hallucinogens	0.00 (0)	0.00 (0)
Opiates	0.00 (0)	0.00 (0)
Others-specify	0.00 (0)	0.00 (0)
COC = Cocaine polydrug users; HC = Healthy Group; % (n) = Percentage and number of the sample who have experienced this event at least once in the last three months.

Table 4

Neuropsychological and Socio-emotional assessment
	HC	COC
Neuropsychological assessment	M (SD)	M (SD)	t (d)
IFS	26.00 (2.28)	20.15 (3.93)	5.59 (1.81)***
IFS-Working Memory	7.53 (1.30)	5.63 (1.67)	3.89 (1.26)***
IFS-Similarities	2.94 (0.22)	2.05 (0.97)	3.91 (1.26)***
IFS-Verbal Fluency	3.00 (0.00)	2.89 (0.31)	1.45 (0.47)
IFS-Motor control	3.00 (0.00)	2.89 (0.31)	1.45 (0.47)
Socio-emotional assessment
IRI	92.78 (9.39)	93.47 (12.03)	-0.20 (-0.06)
IRI–PT	27.73 (4.13)	24.21 (4.42)	2.54 (0.82)*
IRI–PD	13.00 (3.94)	17.42 (6.22)	-2.62 (-0.84)*
IRI–EC	30.52 (4.58)	29.94 (5.38)	0.36 (0.11)
IRI–F	21.52 (4.94)	21.89 (4.14)	-0.25 (-0.08)
SSS-V	17.15 (5.42)	23.63 (5.84)	-3.53 (-1.14)***
SSSV–TAS	4.94 (2.51)	7.05 (2.64)	-2.50 (-0.81)*
SSSV–ES	6.36 (1.70)	7.00 (1.60)	-1.14 (-0.37)
SSSV–D	3.15 (1.70)	4.63 (2.01)	-2.44 (-0.79)*
SSSV–BS	2.68 (1.60)	4.94 (2.41)	-3.41 (-1.10)**
COC = Cocaine poly-drug users; IFS = Ineco Frontal Screening; IFS-WM = Ineco Frontal Screening Working Memory; IRI = Interpersonal Reactivity Index; IRI–PT = Interpersonal Reactivity Index-Perspective Taking; IRI–PD = Interpersonal Reactivity Index–Personal Distress; IRI–EC = Interpersonal Reactivity Index–Empathic Concern; IRI–F = Interpersonal Reactivity Index-Fantasy; SSSV = Sensation Seeking Scale form V; SSSV–TAS = Thrill and adventure seeking; SSSV–ES = Experience seeking; SSSV–D = Disinhibition; SSSV–BS = Boredom susceptibility; * p < .05; p < .01; * p < .001.

Socio-emotional results

The Socio-emotional evaluation did not show significant differences in the total score of Empathy, but HC exhibited a higher score than COC on the Perspective-taking subscale (cognitive dimension) of the IRI. In contrast, COC showed higher scores on the personal distress subscale (affective dimension) of the IRI. Thrill and adventure-seeking, Disinhibition, and Boredom susceptibility subscales of the SSS-V were higher in COC than in HC. No significant differences between groups were observed for the Empathic Concern or Fantasy subscales of the IRI Experience seeking subscale of the SSS-V (See Table 4).

Neuropsychological results

Neuropsychological evaluation using the IFS test showed that HC performed better than COC on the total score of Executive Functions (t (36) = 5.59, p < 0.001, two-tailed); Working Memory subscale (t (36) = 3.88, p < 0.001, two-tailed).

Behavioural results.

Accuracy measure. There are no differences between groups, but global effects across all subjects being Person intentional is more accurate than Person unintentional. A 2 (Target: Person vs. Object) x 2 (Intention: Intentional vs. Unintentional) ANOVA was conducted, including a between-subjects factor of group (HC vs. COC). Comparable to prior work (Escobar et al., 2014), an interaction between target and intentionality was observed [F (1, 36) = 21.64, p < 0.001, η_p² = 0.37]. Post-hoc analysis (Tukey HSD p < 0.001) showed greater accuracy for Person intentional (M = 0.83 SEM = 0.02) than Person unintentional (M = 0.55 SEM = 0.03). Post-hoc tests also showed greater accuracy under Person intentional (M = 0.83 SEM = 0.02) than object unintentional (M = 0.67 SEM = 0.03; Tukey HSD p = 0.004). Despite not finding differences between groups, global differences are a good indicator of the sensitivity of the task.

Reaction times. HC performance is faster than the COC group. A 2 (Target: Person vs. Object) x 2 (Intention: Intentional vs. Unintentional) ANOVA was performed for RT, including a between-subjects factor of group (HC vs. COC). A main effect was observed between subjects [F (1, 36) = 8.79, p = 0.005, η_p² = 0.19; HC had faster reaction times (M = 465 ms; SEM = 47.1) than COC (M = 702 ms; SEM = 64.7).

ERP results

ERP ROI analyses. Based on previous reports of ERPs evoked by socio-affective stimuli related to painful images, we choose three regions of interest, frontal, central, and posterior, as well as different time windows, early 100–200 ms, 200–400 ms and late 400–600, 600–700 ms and 700–800 ms (Escobar et al., 2014a). A 2 (Target: Person vs. Object) x 2 (Intentionality: Intentional vs. Unintentional) x 3 (ROI: frontal vs. central vs. posterior) ANOVA was conducted, including a between-subject factor of group (HC vs. COC) (For other main effect see ERP supplementary data).

The most critical effects observed in our data occurred at 400–600 ms; Target and ROI interacted (F (2, 62) = 5.10, p = 0.009, η² = 0.14). A posthoc analysis (Tukey HSD) revealed that the difference was in the frontal ROI for Person vs object (p < 0.001); here, Person (M = 0.29; SE = 1.03) showed a more positive amplitude than the object (M = -1.33; SE = 1.04). Also, at 600–700 ms: An interaction of Target x Intentionality x ROI (F (2, 62) = 3.27, p = 0.04, η² = 0.08) was observed. A posthoc analysis (Tukey HSD) revealed that the difference was at frontal ROI for Person intentional vs. object unintentional condition (p < 0.001); here, Person intentional (M = 1.68; SE = 1.29) showed a more positive amplitude than object unintentional (M = -0.37; SEM = 1.22).

Significantly, given the absence of group differences and the interactions at frontal ROI, we performed a separate analysis for each group, considering the same factors and time windows.

The most important effects observed in our data occurred at 700–800 ms (Fig. 4a-b). Here, an interaction of Target x Intentionality x ROI [F (2, 32) = 4.00, p = 0.02, η² = 0.20] was observed in HC. A posthoc analysis (Tukey HSD) revealed that the difference was at frontal ROI for person intentional v/s object intentional (p = 0.02); here Person intentional (M = 2.43; SE = 1.06) showed a more positive amplitude than object intentional condition (M = 0.70; SE = 0.85) and for Person intentional v/s object unintentional condition (p = 0.01); here Person intentional (M = 2.43; SE = 1.06) show more positive amplitude than object unintentional condition (M = 0.74; SE = 1.16). This interaction was not observed in the COC group [F (2, 30) = 1.32, p = 0.2, η² = 0.08] (Fig. 3c represents topological activity).

Correlation between ERP's amplitude and Empathy

To explore the relation between neural correlates and Empathy (another critical component in social cognition), we perform a correlation test between the amplitude difference (Δ amplitude) among conditions at Frontal ROI 700–800 ms and the empathic self-report measure (IRI). First, we analyze if there is a difference between Δ amplitudes of groups; no differences were found here (t (32) = -1.43, p = 0.17, two-tailed). However, we observed a positive correlation between Δ amplitude for Person Intentional – Person Unintentional and the total score of empathy scale in HC, r = 0.54, p = 0.01. No correlation was found in the COC group for this ROI at this time window (See Fig. 4).

The consequences of cocaine and stimulant abuse on social and cognitive skills have been well-documented (Cunha et al., 2011; Preller, Herdener, et al., 2014; Preller, Hulka et al., 2014; Tobler et al., 2016; Verdejo-Garcia, 2014). However, no prior work has investigated the neural correlates of intention inference in cocaine polydrug users, which may reflect a socio-cognitive skill underpinning interpersonal behavior. Critically, cocaine abuse and the use of other stimulant drugs have been associated with disruptive social behavior, including violence and rule-breaking (Bungay et al., 2010; Chermack & Blow, 2002; Macdonald et al., 2008; Preller, Hulka, et al., 2014; Walton et al., 2009; Wunderli et al., 2016). Thus, impaired intention inference may partially underpin the relationship between cocaine abuse and maladaptive interpersonal behavior. This study assessed the neural correlates of intention inference, considering persons and objects while controlling for gender, age, educational level, and sociocultural background. We also evaluated other cognitive, social, and psychological traits (executive functions, Empathy, and sensation seeking).

Brain activity does not show differences between groups. However, separate group brain analysis showed that during a late time window (700-800ms) for cortical ERPs at the frontal and central ROI as a marker associated with intentional vs unintentional harm depicted in visual stimuli, HC exhibited a marked amplitude increase for Person intentional relative to object intentional and unintentional (frontal ROI), no such difference was present among COCs. Nevertheless, at 600–700 ms, COCs show a difference associated with an increase for Person intentional relative to object unintentional at central ROI. These results are consistent with other studies showing impairment in frontal brain circuits related to contextual evaluation and decision-making (Escobar et al., 2014a; Hesse et al., 2016; Ibañez & Manes, 2012). While early temporal ERP activity has been associated with automatic brain responses and reflects arousal activity (Brüne et al., 2012; Fan et al., 2014; Lyu et al., 2014), later temporal ERP activity has been associated with more effortful stimulus evaluation and classification. Also, the amplitudes observed at the frontal ROI positively correlated with the total score of Empathy in HC. In contrast, in the case of the COC group, this correlation did not happen. It is possible that neural dynamics related to empathic processes could be altered concerning drug abuse.

Behaviourally, a significant difference was found between groups in reaction time (RT); COC was slower overall than HC. Impaired reaction time has been reported among cocaine users in other experimental settings as well (Fillmore & Rush, 2002).

There was a significant difference between groups in the total score of executive functions (EF), with COC performing worse than HC. Thus, the observed behavioral differences on the IIT could have resulted from an intervention between general differences in EF and specific differences in socio-affective functions. Within the EF, there were differences in working memory and on the similarities test (a measure of abstraction skill), consistent with impairments in global EF. In contrast to previous works (Goldstein et al., 2007; Rojo-Mota et al., 2014), there were no differences in Verbal Fluency or Motor Control. One possible explanation is that affected EF are those related to social skills, such as working memory, inhibition, and abstraction abilities, which could be reflected in social-affective behavior (Schulte et al., 2022).

Consistent with prior work (Mahoney et al., 2015), groups also had significant differences in sensation seeking. Across all domains of sense seeking (thrill and adventure seeking, experience seeking, Disinhibition, and boredom susceptibility), COC was higher than HC. This is very consistent with previous observations among those with substance abuse, in which disinhibition and risk decisions are some of the most characteristic signs (Fillmore, 2012).

Given that IIT differences were not solely attributable to differences in EF, other possible disparities are important avenues for understanding altered behavior among cocaine and stimulant drug users. Interestingly, while there was no significant group difference in global Empathy (measured using the IRI), there was a dissociation between perspective-taking (PT) and personal distress (PD). While HCs exhibited significantly greater PT, COCs exhibited significantly greater PD. Perspective-taking is a cognitive dimension of Empathy, primarily of understanding another person's inner experience (Ruby & Decety, 2001). Personal distress refers to an aversive, self-focused emotional reaction to the apprehension or comprehension of another's emotional state or condition (Davis, 1980, 1983b). The present findings may suggest that altered neurobehavioral patterns among cocaine drug users (i.e., slower RTs, poor differentiation classification of social cues as indexed by late ERP activity) are potentially related to a shift towards emotional over-involvement and away from rational cognitive assessment of social information. Cognitive control and inhibition have a direct impact on behavior.

This study is the first to investigate the neural correlates of intention inference in cocaine polydrug users. This is a growing field in social neuroscience, and several new lines of investigation need to be developed and applied in this population. One limitation of the present study is the small sample size. It is necessary to consider new studies with more sample subjects by group. Interaction effects between groups on main variables were probably found for this reason (because these effects were observed separately for groups). It is challenging to recruit patients and socio-demographically matched participants who fulfill the necessary conditions for this research. However, the same task has been reported using no more than ten subjects and shown to be sensitive (Decety & Cacioppo, 2012b). Another limitation of this study was the absence of a biological marker to confirm recent drug abstinence or use. The medical did characterize the drug use behavior of each participant, somewhat mitigating this concern.

In sum, this is the first study that provides evidence of the difference in neural correlates of intention recognition in a cocaine polydrug sample relative to a sociodemographically matched healthy control group. The COC group showed a diminished performance in Perspective-taking and elevated scores for personal distress vs. the control group; this difference could be interpreted as a poor cognitive evaluation of social cues and an emotional over-involvement. These findings provide a new perspective to study critical social cognitive skills as intention inference in this population, suggesting that work in training socio-emotional regulation may be of clinical benefit. Finally, social context plays a vital role in addictive behavior, and strategies for prevention and treatment should include a socio-emotional focus.

Ethical Approval

The study received prior approval from the ethics committee of Diego Portales University and followed the protocol of the Declaration of Helsinki. Finally, all participants provided a signed consent after reading the information with detailed procedure information.

Funding

This work was supported by grants from Comisión Nacional de Investigación Científica y Tecnológica (ANID/FONDECYT Regular N°1231117 to David Huepe. The funder had no role in deciding to publish or prepare the manuscript.

Availability of data and materials

Data will be available on the GitHub platform once the manuscript has been accepted.

Author Contribution

Juan-Pablo Morales: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing - Original Draft. Nicholas T. Van Dam: Conceptualization, Writing - Original Draft. Daniela Huepe-Artigas: Writing - Review & Editing. Consuelo San-Martin: Conceptualization, Writing - Original Draft. Álvaro Rivera: Software, Writing - Review & Editing. Felipe Rojas: Writing - Review & Editing, Formal analysis. Joaquín Valdés: Writing - Review & Editing, Formal analysis. Agustín Ibáñez: Writing - Review & Editing, Conceptualization. David Huepe: Conceptualization, Resources, Writing - Review & Editing, Supervision, Funding acquisition.

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No competing interests reported.

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Cocaine Polydrug Use and its Impact on Intentional Harm Recognition: A High-Density EEG Study

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Intention inference task (IIT)

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