Understanding effects of the group process on drinking outcomes for emerging adults experiencing homelessness.

BACKGROUND: There is little research on group process for motivational interviewing-based group interventions with young people. We examine how change talk, group climate and cohesion, and facilitator empathy among emerging adults experiencing homelessness affect their drinking outcomes. METHODS: Data come from a clinical trial at three drop-in centers serving emerging adults experiencing homelessness in Los Angeles County and focus on those who received the intervention (n = 132). Participants completed baseline, 3-, 6-, and 12-month follow-up surveys. They were predominantly male and non-white. Group sessions were digitally recorded and coded for percentage change talk (PCT), group climate and cohesion, and facilitator empathy. RESULTS: Because baseline alcohol use was significantly higher at site 1 than sites 2 and 3, we examined associations separately by site. At 6 months, higher PCT was associated with fewer drinks per drinking day for sites 2 and 3, whereas higher PCT was associated with more drinks per drinking day for site 1. There were no effects of PCT at 12 months. Higher group cohesion scores were associated with fewer drinking days at 6 months; higher facilitator empathy was associated with fewer maximum drinks in a day at both 6 and 12 months. Group climate was not associated with drinking outcomes. CONCLUSIONS: These findings highlight the importance of measuring multiple factors in the group process to understand outcomes. What is "uttered" during group and what is observed provide different methods to evaluate the group process and allow us to better bridge the gap between research and practice.

Addictions treatment mechanisms of change science and implementation science: A critical review.

This manuscript aims to contribute to the next phase of mechanisms of behavior change (MOBC) science on alcohol or other drug use. Specifically, we encourage the transition from a basic science orientation (i.e., knowledge generation) to a translational science orientation (i.e., knowledge application or Translational MOBC Science). To inform that transition, we examine MOBC science and implementation science and consider how these two research areas can intersect to capitalize on the goals, strengths, and key methodologies of each. First, we define MOBC science and implementation science and offer a brief historical rationale for these two areas of clinical research. Second, we summarize similarities in rationale and discuss two scenarios where one draws from the other-MOBC science on implementation strategy outcomes and implementation science on MOBC. We then focus on the latter scenario, and briefly review the MOBC knowledge base to consider its readiness for knowledge translation. Finally, we provide a series of research recommendations to facilitate the translation of MOBC science. These recommendations include: (1) identifying and targeting MOBC that are well suited for implementation, (2) use of MOBC research results to inform broader health behavior change theory, and (3) triangulation of a more diverse set of research methodologies to build a translational MOBC knowledge base. Ultimately, it is important for gains borne from MOBC science to affect direct patient care, while basic MOBC research continues to be developed and refined over time. Potential implications of these developments include greater clinical significance for MOBC science, an efficient feedback loop between clinical research methodologies, a multi-level approach to understanding behavioral change, and reduced or eliminated siloes between MOBC science and implementation science.

What can clients tell us about whether to use motivational interviewing? An analysis of early-session ambivalent language.

BACKGROUND: Although motivational interviewing (MI) is an effective method for promoting change in problematic alcohol and other drug use, it does not benefit all clients. Clinicians have little empirical guidance on who is likely to benefit from MI and who is not. We hypothesized that differences in clients' spontaneously offered language early in the session would predict their responsiveness to MI during the remainder of the session. METHOD: The study obtained coding data from 125 counseling sessions from a large randomized controlled trial of clinician training. A cluster analysis created one group of clients whose language reflected ambivalence, and one group whose language reflected readiness to change. We conducted a univariate analysis of variance to compare the mean change in percent change talk across the session between groups. RESULTS: Clients whose language reflected ambivalence early in the session had a greater change in their percent change talk during the remainder of the session, compared to those whose language reflected greater readiness to change (F (1,90) = 63.02, t = 7.94, p < .001). Surprisingly, the group whose language reflected readiness had a decrease in their percent change talk during the remainder of the session (M = -10.9%, SD = 16.3%). Adjusting the results for regression to the mean effects did not eliminate these differences. CONCLUSION: Clients' language early in the session may offer clinicians some guidance on whether MI is likely to be useful or counterproductive in the treatment of substance use disorder.

Can a pure motivational interviewing intervention be manualized and still efficacious? A test of feasibility and initial efficacy.

The importance of attending to the therapeutic process despite the challenges in manualizing it is demonstrated in the empirical evolution of motivational interviewing (MI). Whereas manuals exist for adaptations of MI, no manual has been developed and tested for MI in its pure form (pure MI). This study evaluated the feasibility and initial efficacy of a pure MI intervention manual - MI for risky social drinking (MI-RSD) - designed to target risky social drinking behaviors in college students with social anxiety. A pilot sample of 42 college students completed measures of alcohol use and mental health symptoms and the MI-RSD intervention. We developed a manual for the 2-session MI-RSD intervention, trained 4 clinical doctoral students, and used observer-, therapist- and participant-completed measures to evaluate fidelity. Therapists met beginner proficiency in MI fidelity and participant gave high ratings of therapist adherence to MI and working alliance, demonstrating intervention feasibility. Also, participants reported significant reductions in hazardous drinking and evaluation fears, but not in social interaction anxiety. We offer preliminary evidence that pure MI can be manualized and effective. Specifically, MI-RSD represents an alternative to MI adaptations in mitigating alcohol-related harm for young adults. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Inside Alcohol Behavioral Couple Therapy (ABCT): In-session speech trajectories and drinking outcomes.

The alcohol treatment literature has established in-session client speech as a mechanism of change that therapist behavior can influence and that can predict drinking outcomes. This study aimed to explore temporal patterns of in-session speech in Alcohol Behavioral Couple Therapy (ABCT), including the unique interplay between client and partner speech and the role of speech trajectories in predicting client drinking outcomes. Participants were 165 heterosexual couples receiving ABCT in one of four clinical trials. We coded client speech on an utterance-by-utterance basis using the System for Coding Couples' Interactions in Therapy-Alcohol. We focused on individual-level speech codes of change talk and sustain talk and couple-level variables of positive and negative interactions. We segmented the initial and midtreatment sessions into quartiles to conduct path analyses and latent growth curve models. Path analyses suggested that clients and partners may not have been aligned in terms of treatment goals at the start of the therapy. This misalignment within couples was pronounced during the initial session and decreased by the midtreatment session, reflecting progression toward treatment goals. Of the latent growth curve models, only client sustain talk during the midtreatment session predicted greater client drinking at the end of treatment. Results provide insight into the inner workings of ABCT and suggest recommendations for ABCT therapists. This study also supports a growing consensus that sustain talk may be a stronger mechanism of change than change talk in various alcohol treatment interventions.

A comparison of automated and manual co-registration for magnetoencephalography.

Magnetoencephalography (MEG) is a neuroimaging technique that accurately captures the rapid (sub-millisecond) activity of neuronal populations. Interpretation of functional data from MEG relies upon registration to the participant's anatomical MRI. The key remaining step is to transform the participant's MRI into the MEG head coordinate space. Although both automated and manual approaches to co-registration are available, the relative accuracy of two approaches has not been systematically evaluated. The goal of the present study was to compare the accuracy of manual and automated co-registration. Resting MEG and T1-weighted MRI data were collected from 90 participants. Automated and manual co-registration were performed on the same subjects, and the inter-method reliability of the two methods assessed using the intra-class correlation. Median co-registration error for both methods was within acceptable limits. Inter-method reliability was in the "good" range for co-registration error, and the "good" to "excellent" range for translation and rotation. These results suggest that the output of the automated co-registration procedure is comparable to that achieved using manual co-registration.

Discordant Alpha-Band Transcranial Alternating Current Stimulation Affects Cortico-Cortical and Cortico-Cerebellar Connectivity.

Synchronization of oscillatory brain activity is believed to play a critical role in linking distributed neuronal populations into transient functional networks. Alpha-band alternating current stimulation (tACS) was applied over bilateral parietal cortex in a double-blind sham-controlled study to test the notion that widespread alpha mediates causal relationships in the gamma-band both within local neuronal populations and also across distant brain regions. Causal relationships of oscillatory alpha- and gamma-band activity were characterized during performance of a visual global/local attention task. Nonfocal and nonphase-locked tACS, discordant with endogenous oscillatory activity, was hypothesized to induce a performance deficit and differences in network-level causal relationships between both cortical and subcortical brain regions. Although modulation of fronto-parieto-cerebellar causal relationships was observed following stimulation, there was no evidence for a behavioral deficit. We propose that olivo-cerebellar circuits may have responded to the discordant tACS-induced currents as if they were "error signals" in the context of ongoing functional alpha-band brain dynamics. Compensatory cerebellar activity may have contributed to the lack of behavioral deficits and to differences in causal relationships observed following stimulation. Understanding a potential compensatory mechanism involving short-term plasticity in the cerebellum may be critical to developing potential clinical applications of tACS, particularly for disorders such as autism that are characterized by both atypical cortical and cerebellar dynamics.

Dynamic Functional Network Connectivity in Schizophrenia with Magnetoencephalography and Functional Magnetic Resonance Imaging: Do Different Timescales Tell a Different Story?

The importance of how brain networks function together to create brain states has become increasingly recognized. Therefore, an investigation of eyes-open resting-state dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) via both functional magnetic resonance imaging (fMRI) and a novel magnetoencephalography (MEG) pipeline was completed. The fMRI analysis used a spatial independent component analysis (ICA) to determine the networks on which the dFNC was based. The MEG analysis utilized a source space activity estimate (minimum norm estimate [MNE]/dynamic statistical parametric mapping [dSPM]) whose result was the input to a spatial ICA, on which the networks of the MEG dFNC were based. We found that dFNC measures reveal significant differences between HC and SP, which depended on the imaging modality. Consistent with previous findings, a dFNC analysis predicated on fMRI data revealed HC and SP remain in different overall brain states (defined by a k-means clustering of network correlations) for significantly different periods of time, with SP spending less time in a highly connected state. The MEG dFNC, in contrast, revealed group differences in more global statistics: SP changed between meta-states (k-means cluster states that are allowed to overlap in time) significantly more often and to states that were more different, relative to HC. MEG dFNC also revealed a highly connected state where a significant difference was observed in interindividual variability, with greater variability among SP. Overall, our results show that fMRI and MEG reveal between-group functional connectivity differences in distinct ways, highlighting the utility of using each of the modalities individually, or potentially a combination of modalities, to better inform our understanding of disorders such as schizophrenia.

Examining the influence of active ingredients of motivational interviewing on client change talk.

Motivational Interviewing (MI) is an evidenced-based intervention designed to help clients explore and resolve ambivalence around substance use. MI combines a humanistic tradition with behavioral components to facilitate client decisions concerning behavior change. As such, there is marked interest in the relationship between the two active ingredients of MI - the relational, or person-centered, components and the technical, or directional, behavioral components - on client in-session language. Yet, few studies have examined how these active ingredients operate in concert. Therefore, the current study evaluated the constellation of relational skills associated with client language, as well as the influence of technical skills on the relationship between provider relational skills and client change language. Specifically, we tested a latent construct of relational skill and its direct association with the proportion of client change talk. We then explored the mediating role of reflections of change and sustain talk (RefCT and RefST) on this relationship. The data for this secondary analysis are from Project ELICIT (N = 131), a randomized control trial evaluating the effects of MI training on client change language. We found support for a latent construct of relational skill (i.e., empathy, acceptance, collaboration, and autonomy/support). However, the relational skill construct did not predict client change language. There was support for an indirect effect, such that relational skills predicted RefCT and RefST, and RefCT and RefST predicted client change language. These results suggest that the synergistic implementation of the relational and technical components of MI is critical to facilitating a higher percentage of change talk.

Short- and Long-Term Effects of Within-Session Client Speech on Drinking Outcomes in the COMBINE Study.

OBJECTIVE: There is evidence of a causal chain in motivational interviewing (MI) involving counselor MI-consistent skills, client change language, and outcomes. MI was a key component of the combined behavioral intervention in the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study. Participants in COMBINE were treatment-seeking and medication-seeking, and were required to maintain a period of abstinence before enrollment. Counselors were closely monitored and were temporarily removed from the study for remediation and supervision if their performance fell below threshold. The purpose of this study was to evaluate the MI causal chain among initial-session combined behavioral intervention audio recordings in this unique sample of highly motivated clients and highly monitored counselors. METHOD: Session 1 audio recordings (N = 254, 73.5% men) were evaluated using the Motivational Interviewing Skill Code Version 2.0 with good interrater reliability. Counselor speech was measured using a summary measure of MI-consistent behavior. Client change language was assessed, using change talk and sustain talk. The outcome measure of drinks per week was computed using the COMBINE data set. RESULTS: Higher sustain talk was significantly associated with increased drinking during treatment, whereas higher change talk was significantly associated with decreased drinking at the 1-year follow-up. In addition, there were significant indirect effects linking counselor behavior, client speech, and drinking both during treatment and at 1 year. CONCLUSIONS: Results supported the posited causal chain for MI. Despite somewhat lower variability of counselor behavior and use of a coding instrument that did not capture directional counselor behaviors, counselor behavior, client speech, and drinking outcomes were clearly linked in this unique sample.

The language of change among criminal justice clients: Counselor language, client language, and client substance use outcomes.

OBJECTIVE: Counselor and client language have been identified as mechanisms of change in motivational interviewing (MI) counseling sessions. This study evaluated whether language patterns exhibited during MI sessions with substance users in the community would also be found during MI sessions with substance users in the criminal justice system. METHOD: Forty audio recordings of MI sessions with substance-using probationers were coded and analyzed sequentially using the Motivational Interviewing Skills Code (MISC) 2.5. Analyses examined the relationship between counselor and client language, and the relationship between client language and client substance use after 2 months. RESULTS: Counselor MI inconsistent language was associated with decreased change talk (lnOR = - 0.76, p < .05) though not with increased sustain talk. Both sustain talk (b = - 4.591, t = - 18.634 p < .001) and MI inconsistent language MIIN (b = - 4.419, t = - 19.886, p < .001) were positively associated with substance use at 2 months. Sustain talk early in the session (i.e., during deciles 1 and 2) was significantly greater among clients who reported using substances at 2 months, compared to clients who did not use substances. CONCLUSION: These findings are broadly consistent with previous literature documenting the association between counselor language, client language, and client outcome.

Working memory capacity and addiction treatment outcomes in adolescents.

BACKGROUND: Brief addiction treatments including motivational interviewing (MI) have shown promise with adolescents, but the factors that influence treatment efficacy in this population remain unknown. One candidate is working memory, the ability to hold a fact or thought in mind. This is relevant, as in therapy, a client must maintain and manipulate ideas while working with a clinician. Working memory depends upon brain structures and functions that change markedly during neurodevelopment and that can be negatively impacted by substance use. OBJECTIVES: In a secondary analysis of data from a clinical trial for adolescent substance use comparing alcohol/marijuana education and MI, we evaluated the relationship between working memory and three-month treatment-outcomes with the hypothesis that the relationship between intervention conditions and outcome would be moderated by working memory. METHODS: With a diverse sample of adolescents currently using alcohol and/or marijuana (N = 153, 64.7% male, 70.6% Hispanic), we examined the relationship between baseline measures of working memory and alcohol and cannabis-related problem scores measured at the three-month follow-up. RESULTS: The results showed that lower working memory scores were associated with poorer treatment response only for alcohol use, and only within the education group. No relationship was found between working memory and treatment outcomes in the MI group. CONCLUSION: The results suggest that issues with working memory capacity may interfere with adolescents' ability to process and implement didactic alcohol and marijuana content in standard education interventions. These results also suggest that MI can be implemented equally effectively across the range of working memory functioning in youth.

Group motivational interviewing for homeless young adults: Associations of change talk with substance use and sexual risk behavior.

Homeless young adults exhibit high rates of alcohol and other drug (AOD) use and sexual risk behaviors. This study is a secondary analysis of data collected in a randomized clinical trial of AWARE, a new 4 session group motivational interviewing intervention. AWARE mainly focused on alcohol use and sexual risk behavior given focus group feedback. We used sequential coding to analyze how the group process affected both AOD use and sexual risk behavior at 3-month follow up among homeless young adults by examining facilitator behavior and participant change talk (CT) and sustain talk (ST). We analyzed 57 group session digital recordings of 100 youth (69% male, 74% heterosexual, 28% non-Hispanic white, 23% African American, 26% Hispanic, 23% multiracial/other; mean age 21.75). Outcomes included importance and readiness to change AOD use and risky sexual behavior, AOD use and consequences, number of partners and unprotected sex, and condom self-efficacy. Sequential analysis indicated that facilitator open-ended questions and reflections of CT increased Group CT. Group CT was associated with a lower likelihood of being a heavy drinker 3 months later; Group ST was associated with decreased readiness and confidence to change alcohol use. There were no associations with CT or ST for drug use or risky sexual behavior. Facilitator speech and peer responses were related to CT and ST during the group sessions with this high risk population, which were then associated with individual changes for alcohol use. Further research is needed to explore associations with drug use and sexual risk behavior. (PsycINFO Database Record

Diminished auditory sensory gating during active auditory verbal hallucinations.

Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH.

A randomized controlled trial to influence client language in substance use disorder treatment.

BACKGROUND: Client language is hypothesized to be a mechanism of action in motivational interviewing (MI). Despite the association of change and sustain talk with substance treatment outcomes, it not known whether providers can intentionally influence this language as hypothesized. OBJECTIVE: This is a randomized controlled trial to investigate whether substance use providers can be trained to influence client language. METHODS: Treatment providers specializing in substance use disorders (n=190) were randomly assigned to standard training in MI (MI-AU) or training emphasizing an influence of client language (MI-LEAF). Treatment sessions with actual clients were evaluated 3, 6 and 12 months after training by masked raters. Frequencies of client change and sustain talk were the outcome variables. RESULTS: Sustain talk, but not change talk, was significantly lower in clients whose providers had received the specialized training (b=-0.175, SE=0.087, p=0.046, CI[-0.348 to 0.002], d=-0.325). Mediation analyses supported a causal chain between a) training, b) providers' attempts to minimize sustain talk in treatment sessions via directive reflective listening and c) client sustain talk in the treatment session (κ2=0.0833, bootstrap SE=0.0394, 95% CI [0.0148, 0.1691]). CONCLUSIONS: With specialized training, providers can reduce the amount of opposition language their clients offer when considering a change in their substance use. Demonstrating that client language is under partial control of the provider supports the feasibility of clinical trials to investigate the impact of shaping client language on treatment outcomes.

Magnetoencephalographic and functional MRI connectomics in schizophrenia via intra- and inter-network connectivity.

Examination of intrinsic functional connectivity using functional MRI (fMRI) has provided important findings regarding dysconnectivity in schizophrenia. Extending these results using a complementary neuroimaging modality, magnetoencephalography (MEG), we present the first direct comparison of functional connectivity between schizophrenia patients and controls, using these two modalities combined. We developed a novel MEG approach for estimation of networks using MEG that incorporates spatial independent component analysis (ICA) and pairwise correlations between independent component timecourses, to estimate intra- and intern-network connectivity. This analysis enables group-level inference and testing of between-group differences. Resting state MEG and fMRI data were acquired from a large sample of healthy controls (n=45) and schizophrenia patients (n=46). Group spatial ICA was performed on fMRI and MEG data to extract intrinsic fMRI and MEG networks and to compensate for signal leakage in MEG. Similar, but not identical spatial independent components were detected for MEG and fMRI. Analysis of functional network connectivity (FNC; i.e., pairwise correlations in network (ICA component) timecourses) revealed a differential between-modalities pattern, with greater connectivity among occipital networks in fMRI and among frontal networks in MEG. Most importantly, significant differences between controls and patients were observed in both modalities. MEG FNC results in particular indicated dysfunctional hyperconnectivity within frontal and temporal networks in patients, while in fMRI FNC was always greater for controls than for patients. This is the first study to apply group spatial ICA as an approach to leakage correction, and as such our results may be biased by spatial leakage effects. Results suggest that combining these two neuroimaging modalities reveals additional disease-relevant patterns of connectivity that were not detectable with fMRI or MEG alone.

Multimodal Classification of Schizophrenia Patients with MEG and fMRI Data Using Static and Dynamic Connectivity Measures.

Mental disorders like schizophrenia are currently diagnosed by physicians/psychiatrists through clinical assessment and their evaluation of patient's self-reported experiences as the illness emerges. There is great interest in identifying biological markers of prognosis at the onset of illness, rather than relying on the evolution of symptoms across time. Functional network connectivity, which indicates a subject's overall level of "synchronicity" of activity between brain regions, demonstrates promise in providing individual subject predictive power. Many previous studies reported functional connectivity changes during resting-state using only functional magnetic resonance imaging (fMRI). Nevertheless, exclusive reliance on fMRI to generate such networks may limit the inference of the underlying dysfunctional connectivity, which is hypothesized to be a factor in patient symptoms, as fMRI measures connectivity via hemodynamics. Therefore, combination of connectivity assessments using fMRI and magnetoencephalography (MEG), which more directly measures neuronal activity, may provide improved classification of schizophrenia than either modality alone. Moreover, recent evidence indicates that metrics of dynamic connectivity may also be critical for understanding pathology in schizophrenia. In this work, we propose a new framework for extraction of important disease related features and classification of patients with schizophrenia based on using both fMRI and MEG to investigate functional network components in the resting state. Results of this study show that the integration of fMRI and MEG provides important information that captures fundamental characteristics of functional network connectivity in schizophrenia and is helpful for prediction of schizophrenia patient group membership. Combined fMRI/MEG methods, using static functional network connectivity analyses, improved classification accuracy relative to use of fMRI or MEG methods alone (by 15 and 12.45%, respectively), while combined fMRI/MEG methods using dynamic functional network connectivity analyses improved classification up to 5.12% relative to use of fMRI alone and up to 17.21% relative to use of MEG alone.

Functional MRI Evaluation of Multiple Neural Networks Underlying Auditory Verbal Hallucinations in Schizophrenia Spectrum Disorders.

Functional MRI studies have identified a distributed set of brain activations to be associated with auditory verbal hallucinations (AVH). However, very little is known about how activated brain regions may be linked together into AVH-generating networks. Fifteen volunteers with schizophrenia or schizoaffective disorder pressed buttons to indicate onset and offset of AVH during fMRI scanning. When a general linear model was used to compare blood oxygenation level dependence signals during periods in which subjects indicated that they were versus were not experiencing AVH ("AVH-on" versus "AVH-off"), it revealed AVH-related activity in bilateral inferior frontal and superior temporal regions; the right middle temporal gyrus; and the left insula, supramarginal gyrus, inferior parietal lobule, and extranuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICAs). Four ICA components were spatially consistent with an a priori network framework based upon published meta-analyses of imaging correlates of AVH. Of these four components, only a network involving bilateral auditory cortices and posterior receptive language areas was significantly and positively correlated to the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial prefrontal), not fully matching the meta-analysis framework, but nevertheless containing nodes reported as active in some studies of AVH. Both networks showed significant AVH-related profiles, but both were most active during AVH-off periods. Overall, the data suggest that AVH generation requires specific and selective activation of auditory cortical and posterior language regions, perhaps coupled to a release of indirect influence by occipital and medial frontal structures.