Constructs derived from the addiction cycle predict alcohol use disorder treatment outcomes and recovery 3 years following treatment.

OBJECTIVE: The addiction cycle has been proposed as a framework for understanding the progression of alcohol use disorder (AUD) in terms of psychological and biological domains, including reward drinking/incentive salience, relief drinking/negative emotionality, and loss of control/executive functioning impairment. To have utility in clinical practice, self-report measures of these domains that are applicable across sociodemographic groups and associated with clinical outcomes are needed. This study sought to validate domains from self-report measures and to test whether domains are measurement invariant across sociodemographic groups and associated with treatment outcomes. METHOD: Secondary analysis of individuals with AUD (n = 3,092) who participated in two alcohol clinical trials, Project Matching Alcohol Treatment to Client Heterogeneity (MATCH) and COMBINE. Factor analytic methods were used to derive addiction cycle domains at baseline. These domains were then examined as predictors of outcomes. RESULTS: Fifteen self-report items were used as indicators of the addiction cycle domains, with sociodemographic differences in measurement by sex, age, race, education, and AUD symptoms. Relief/negative emotionality and reward/incentive salience were significantly associated with outcomes at 1 and 3 years following treatment, and executive functioning also predicted nonabstinent recovery at 3 years. CONCLUSIONS: The results support the utility of domains relevant to the addiction cycle in predicting AUD treatment outcomes and recovery among individuals who sought treatment for AUD. The addiction cycle domains were more strongly associated with outcomes than other measures clinicians might use to predict outcomes (e.g., AUD symptoms). Future research should continue to develop and refine the items and test whether the addiction cycle domains can inform treatment planning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Electric field distribution predicts efficacy of accelerated intermittent theta burst stimulation for late-life depression.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for late-life depression (LLD) but may have lower rates of response and remission owing to age-related brain changes. In particular, rTMS induced electric field strength may be attenuated by cortical atrophy in the prefrontal cortex. To identify clinical characteristics and treatment parameters associated with response, we undertook a pilot study of accelerated fMRI-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex in 25 adults aged 50 or greater diagnosed with LLD and qualifying to receive clinical rTMS. Methods: Participants underwent baseline behavioral assessment, cognitive testing, and structural and functional MRI to generate individualized targets and perform electric field modeling. Forty-five sessions of iTBS were delivered over 9 days (1800 pulses per session, 50-min inter-session interval). Assessments and testing were repeated after 15 sessions (Visit 2) and 45 sessions (Visit 3). Primary outcome measure was the change in depressive symptoms on the Inventory of Depressive Symptomatology-30-Clinician (IDS-C-30) from Visit 1 to Visit 3. Results: Overall there was a significant improvement in IDS score with the treatment (Visit 1: 38.6; Visit 2: 31.0; Visit 3: 21.3; mean improvement 45.5%) with 13/25 (52%) achieving response and 5/25 (20%) achieving remission (IDS-C-30 < 12). Electric field strength and antidepressant effect were positively correlated in a subregion of the ventrolateral prefrontal cortex (VLPFC) (Brodmann area 47) and negatively correlated in the posterior dorsolateral prefrontal cortex (DLPFC). Conclusion: Response and remission rates were lower than in recently published trials of accelerated fMRI-guided iTBS to the left DLPFC. These results suggest that sufficient electric field strength in VLPFC may be a contributor to effective rTMS, and that modeling to optimize electric field strength in this area may improve response and remission rates. Further studies are needed to clarify the relationship of induced electric field strength with antidepressant effects of rTMS for LLD.

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder.

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

A review of functional brain differences predicting relapse in substance use disorder: Actionable targets for new methods of noninvasive brain stimulation.

Neuroimaging studies have identified a variety of brain regions whose activity predicts substance use (i.e., relapse) in patients with substance use disorder (SUD), suggesting that malfunctioning brain networks may exacerbate relapse. However, this knowledge has not yet led to a marked improvement in treatment outcomes. Noninvasive brain stimulation (NIBS) has shown some potential for treating SUDs, and a new generation of NIBS technologies offers the possibility of selectively altering activity in both superficial and deep brain structures implicated in SUDs. The goal of the current review was to identify deeper brain structures involved in relapse to SUD and give an account of innovative methods of NIBS that might be used to target them. Included studies measured fMRI in currently abstinent SUD patients and tracked treatment outcomes, and fMRI results were organized with the framework of the Addictions Neuroclinical Assessment (ANA). Four brain structures were consistently implicated: the anterior and posterior cingulate cortices, ventral striatum and insula. These four deeper brain structures may be appropriate future targets for the treatment of SUD using these innovative NIBS technologies.

Transcranial Direct Current Stimulation Provides no Additional Benefit to Improvements in Self-Reported Craving Following Mindfulness-Based Relapse Prevention.

Objectives: Mindfulness-Based Relapse Prevention (MBRP) and transcranial direct current stimulation (tDCS) have each demonstrated efficacy in improving outcomes in those with alcohol use disorder (AUD), however a recent study that combined MBRP with tDCS found tDCS provided no additional benefit to MBRP for AUD. Differences in treatment adherence between active versus sham tDCS groups may have contributed to this result. The current study examined whether treatment adherence interacted with tDCS condition in predicting post-treatment mindfulness and craving. Methods: This study was a secondary data analysis from a randomized sham-controlled trial comparing MBRP paired with tDCS. Linear regression analyses were conducted examining the interaction between tDCS condition and two measures of treatment adherence (i.e., number of groups attended, number of tDCS administrations) on post-treatment mindfulness and craving. Results: There was no effect of treatment adherence by tDCS condition in predicting mindfulness, however the interaction between treatment adherence and tDCS condition significantly predicted post-treatment craving. There was a significant negative association between treatment adherence and post-treatment craving in the sham group, but there was no association in the active tDCS group. Conclusions: MBRP coupled with sham stimulation led to significant reductions in self-reported craving when patients attended more sessions and received a greater number of sham tDCS administrations, while no relationship was observed between treatment adherence and craving among those who received active tDCS. This result provides tentative evidence that, rather than improve the effects of MBRP on craving, this active tDCS protocol provides no additional benefit to MBRP in reducing craving. Pre-registration: This study was registered with clinicaltrials.gov (NCT02861807).

Baseline Differences in Anxiety Affect Attention and tDCS-Mediated Learning.

Variable responses to transcranial direct current stimulation (tDCS) protocols across individuals are widely reported, but the reasons behind this variation are unclear. This includes tDCS protocols meant to improve attention. Attentional control is impacted by top-down and bottom-up processes, and this relationship is affected by state characteristics such as anxiety. According to Attentional Control Theory, anxiety biases attention towards bottom-up and stimulus-driven processing. The goal of this study was to explore the extent to which differences in state anxiety and related measures affect visual attention and category learning, both with and without the influence of tDCS. Using discovery learning, participants were trained to classify pictures of European streets into two categories while receiving 30 min of 2.0 mA anodal, cathodal, or sham tDCS over the rVLPFC. The pictures were classifiable according to two separate rules, one stimulus and one hypothesis-driven. The Remote Associates Test (RAT), Profile of Mood States, and Attention Networks Task (ANT) were used to understand the effects of individual differences at baseline on subsequent tDCS-mediated learning. Multinomial logistic regression was fit to predict rule learning based on the baseline measures, with subjects classified according to whether they used the stimulus-driven or hypothesis-driven rule to classify the pictures. The overall model showed a classification accuracy of 74.1%. The type of tDCS stimulation applied, attentional orienting score, and self-reported mood were significant predictors of different categories of rule learning. These results indicate that anxiety can influence the quality of subjects' attention at the onset of the task and that these attentional differences can influence tDCS-mediated category learning during the rapid assessment of visual scenes. These findings have implications for understanding the complex interactions that give rise to the variability in response to tDCS.

Quantifying the Difference between Active and Passive Control Groups in Cognitive Interventions Using two Meta-Analytical Approaches.

Despite promising reports of broad cognitive benefit in studies of cognitive training, it has been argued that the reliance of many studies on no-intervention control groups (passive controls) make these reports difficult to interpret because placebo effects cannot be ruled out. Although researchers have recently been trying to incorporate more active controls, in which participants engage in an alternate intervention, previous work has been contentious as to whether this actually yields meaningfully different results. To better understand the influence of passive and active control groups on cognitive interventions, we conducted two meta-analyses to estimate their relative effect sizes. While the first one broadly surveyed the literature by compiling data from 34 meta-analyses, the second one synthesized data from 42 empirical studies that simultaneously employed both types of controls. Both analyses showed no meaningful performance difference between passive and active controls, suggesting that current active control placebo paradigms might not be appropriately designed to reliably capture these non-specific effects or that these effects are minimal in this literature.

Transcranial direct current stimulation facilitates category learning.

BACKGROUND: After two decades of transcranial direct current stimulation (tDCS) research, it is still unclear which applications benefit most from which tDCS protocols. One prospect is the acceleration of learning, where previous work has demonstrated that anodal tDCS applied to the right ventrolateral prefrontal cortex (rVLPFC) is capable of doubling the rate of learning in a visual camouflaged threat detection and category learning task. GOALS: Questions remain as to the specific cognitive mechanisms underlying this learning enhancement, and whether it generalizes to other tasks. The goal of the current project was to expand previous findings by employing a novel category learning task. METHODS: Participants learned to classify pictures of European streets within a discovery learning paradigm. In a double-blind design, 54 participants were randomly assigned to 30 min of tDCS using either 2.0 mA anodal (n = 18), cathodal (n = 18), or 0.1 mA sham (n = 18) tDCS over the rVLPFC. RESULTS: A linear mixed-model revealed a significant effect of tDCS condition on classification accuracy across training (p = 0.001). Compared to a 4.2% increase in sham participants, anodal tDCS over F10 increased performance by 20.6% (d = 1.71) and cathodal tDCS by 14.4% (d = 1.16). CONCLUSIONS: These results provide further evidence for the capacity of tDCS applied to rVLPFC to enhance learning, showing a greater than quadrupling of test performance after training (491% of sham) in a difficult category learning task. Combined with our previous studies, these results suggest a generalized performance enhancement. Other tasks requiring sustained attention, insight and/or category learning may also benefit from this protocol.

Non-invasive brain stimulation in substance use disorders: implications for dissemination to clinical settings.

With expanding knowledge of how neural circuitry is disrupted in substance use disorders (SUD), non-invasive brain stimulation (NIBS) techniques have emerged as potential strategies to directly modulate those neural circuits. There is some evidence supporting the two most common forms of NIBS, transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), in the treatment of SUD. Yet results of recent studies have been mixed and critical methodological issues must be addressed before strong conclusions can be drawn. This review highlights recent evidence of NIBS for SUD, addressing the impact of stimulation on relevant clinical and cognitive outcomes in substance-using populations. Additionally, we aim to bring a clinical perspective to the opportunities and challenges of implementing neuromodulation in SUD treatment.

Increased Excitability Induced in the Primary Motor Cortex by Transcranial Ultrasound Stimulation.

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS is currently unknown. Objective: We aimed to examine the effects of a commercial diagnostic tUS device using an imaging protocol on cortical excitability. We hypothesized that imaging tUS applied to motor cortex could induce changes in cortical excitability as measured using a transcranial magnetic stimulation (TMS) motor evoked potential (MEP) paradigm. Methods: Forty-three subjects were assigned to receive either verum (n = 21) or sham (n = 22) diagnostic tUS in a single-blind design. Baseline motor cortex excitability was measured using MEPs elicited by TMS. Diagnostic tUS was subsequently administered to the same cortical area for 2 min, immediately followed by repeated post-stimulation MEPs recorded up to 16 min post-stimulation. Results: Verum tUS increased excitability in the motor cortex (from baseline) by 33.7% immediately following tUS (p = 0.009), and 32.4% (p = 0.047) 6 min later, with excitability no longer significantly different from baseline by 11 min post-stimulation. By contrast, subjects receiving sham tUS showed no significant changes in MEP amplitude. Conclusion: These findings demonstrate that tUS delivered via a commercially available diagnostic imaging ultrasound system transiently increases excitability in the motor cortex as measured by MEPs. Diagnostic tUS devices are currently used for internal imaging in many health care settings, and the present results suggest that these same devices may also offer a promising tool for noninvasively modulating activity in the central nervous system. Further studies exploring the use of diagnostic imaging devices for neuromodulation are warranted.

The Benefits of Closed-Loop Transcranial Alternating Current Stimulation on Subjective Sleep Quality.

BACKGROUND: Poor sleep quality is a common complaint, affecting over one third of people in the United States. While sleep quality is thought to be related to slow-wave sleep (SWS), there has been little investigation to address whether modulating slow-wave oscillations (SWOs) that characterize SWS could impact sleep quality. Here we examined whether closed-loop transcranial alternating current stimulation (CL-tACS) applied during sleep impacts sleep quality and efficiency. METHODS: CL-tACS was used in 21 participants delivered at the same frequency and in phase with endogenous SWOs during sleep. Sleep quality was assessed in the morning following either verum or sham control stimulation during sleep, with order counterbalanced within participants. RESULTS: Higher sleep quality and efficiency were found after verum stimulation nights compared to control. The largest effects on sleep quality were found immediately following an adaptation night in the laboratory for which sleep quality was reduced. CONCLUSIONS: Applying CL-tACS at the same frequency and phase as endogenous SWOs may offer a novel method to improve subjective sleep quality after a night with poor quality sleep. CL-tACS might be helpful for increasing sleep quality and efficiency in otherwise healthy people, and in patients with clinical disorders that involve sleep deficits.