Prescription opioids are a primary driver of opioid-related deaths. Although craving is a substantial component of OUD, the degree to which craving leads to misuse among chronic pain patients on ...long-term prescription opioids is unknown. A clear understanding of the factors that lead to misuse in this vulnerable population is needed for the development of safe and effective practices for opioid taper. This narrative review summarizes the relevant literature on the role of craving in addiction and chronic pain through epidemiological and behavioral studies. The first part of this review examines the role of craving in predicting opioid use/misuse in individuals with chronic pain with and without OUD. The second part covers methods on how craving is evaluated experimentally using both subjective and objective measures and provides related findings. The overall goal of this review is to facilitate the development of a population-specific description of craving in those who use opioids to control chronic pain and to describe how it may be mechanistically linked to patterns of opioid (mis)use.
•The concept of craving is complex, subjective, with heterogeneous etiologies.•The degree to which craving plays a role in opioid consumption in chronic pain is poorly understood.•Severity of psychiatric symptoms are associated with higher craving and greater opioid (mis)use among chronic pain patients.•There is little evidence that pain severity reinforces opioid craving and (mis)use in chronic pain.•Currently available measures to assess craving may translate poorly to chronic pain patients.
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven ...subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy.
In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment.
We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption.
Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.
Posttraumatic stress disorder (PTSD) is associated with inhibitory control dysfunction that extends beyond difficulties inhibiting trauma‐related intrusions. Inhibitory learning has been proposed as ...a potential mechanism of change underlying the effectiveness of extinction‐based therapies such as prolonged exposure (PE), a first‐line treatment for PTSD. To identify neurocognitive markers of change in inhibitory learning associated with PE, we applied a Bayesian learning model to the analysis of neuroimaging data collected during an inhibitory control task, both before and after PE treatment. Veterans (N = 20) with combat‐related PTSD completed a stop‐signal task (SST) while undergoing fMRI at time points immediately before and after PE treatment. Participants exhibited a small, significant improvement in performance on the SST, as demonstrated by longer reaction times and improved inhibition accuracy. Amplitude of neural activation associated with a signed prediction error (SPE; i.e., the discrepancy between actual outcome and model‐based expectation of needing to stop) in the right caudate decreased from baseline to posttreatment assessment. Change in model‐based activation was modulated by performance accuracy, with a decrease in positive SPE activation observed on successful trials, d = 0.79, and a reduction in negative SPE activation on error trials, d = 0.74. The decrease in SPE‐related activation on successful stop trials was correlated with PTSD symptom reduction. These results are consistent with the notion that PE may help broadly strengthen inhibitory learning and the development of more accurate model‐based predictions, which may thus facilitate change in cognitions in response to trauma‐related cues and help reduce PTSD symptoms.
Abstract Background Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the ...hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement. Methods Thirty eight adolescents from local area middle schools, ages 12–14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n = 21), or as healthy controls (CON; n = 17). Results At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p < .01, each cluster ≥32 contiguous voxels). Conclusions These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use.
•Anticipatory reactivity to trauma cues is high in comorbid PTSD and alcohol use.•This affective hyperactivation may be reduced by cognitive-behavioral treatments.•After treatment, anticipatory ...activity changed in two salience network regions.•These activation changes were positively related to PTSD symptom severity change.•Treatment (exposure vs non-exposure) was not additionally related to neural changes.
Post-traumatic stress disorder (PTSD) is associated with neuro-physiological abnormalities reflecting increased anticipatory anxiety and reactivity to traumatic cues. It remains unclear whether neural mechanisms associated with PTSD treatment responsiveness, i.e. hyperactivation of the affective salience network in the brain, extend to a comorbid PTSD and substance use disorder population.
Thirty-one Veterans with PTSD and co-occurring alcohol use disorder (AUD) were randomly assigned to either prolonged exposure or a non-exposure based treatment. They completed an affective anticipation task while undergoing fMRI, immediately prior and after completing treatment.
After controlling for type and length of treatment, larger reduction of PTSD symptoms was associated with decreased anticipatory activation to negative trauma-related cues in the right pre-Supplementary Motor Area (pre-SMA), a region associated with emotion regulation. Smaller reduction in PTSD severity was associated with enhanced anticipatory activation to those cues within the right para-hippocampal region, an affective processing region.
Our findings suggest that post-treatment reductions in anticipatory reactivity to trauma-related cues in the pre-SMA and para-hippocampal area are associated with larger PTSD symptom reduction in individuals with co-occurring PTSD and AUD. These results may offer neurofeedback training targets as an alternative to or enhancement of other PTSD treatment modalities in this population.
The extent to which one can use cognitive resources to keep information in working memory is known to rely on (1) active maintenance of target representations and (2) downregulation of interference ...from irrelevant representations. Neurobiologically, the global capacity of working memory is thought to depend on the prefrontal and parietal cortices; however, the neural mechanisms involved in controlling interference specifically in working memory capacity tasks remain understudied. In this study, 22 healthy participants completed a modified complex working memory capacity task (Reading Span) with trials of varying levels of interference control demands while undergoing functional MRI. Neural activity associated with interference control demands was examined separately during encoding and recall phases of the task. Results suggested a widespread network of regions in the prefrontal, parietal, and occipital cortices, and the cingulate and cerebellum associated with encoding, and parietal and occipital regions associated with recall. Results align with prior findings emphasizing the importance of frontoparietal circuits for working memory performance, including the role of the inferior frontal gyrus, cingulate, occipital cortex, and cerebellum in regulation of interference demands.
Background
Recent studies in both human and experimental animals have identified fragmented and unpredictable parental and environmental signals as a novel source of early‐life adversity. Early‐life ...unpredictability may be a fundamental developmental factor that impacts brain development, including reward and emotional memory circuits, affecting the risk for psychopathology later in life. Here, we tested the hypothesis that self‐reported early‐life unpredictability is associated with psychiatric symptoms in adult clinical populations.
Methods
Using the newly validated Questionnaire of Unpredictability in Childhood, we assessed early‐life unpredictability in 156 trauma‐exposed adults, of which 65% sought treatment for mood, anxiety, and/or posttraumatic stress disorder (PTSD) symptoms. All participants completed symptom measures of PTSD, depression and anhedonia, anxiety, alcohol use, and chronic pain. Relative contributions of early‐life unpredictability versus childhood trauma and associations with longitudinal outcomes over a 6‐month period were determined.
Results
Early‐life unpredictability, independent of childhood trauma, was significantly associated with higher depression, anxiety symptoms, and anhedonia, and was related to higher overall symptom ratings across time. Early‐life unpredictability was also associated with suicidal ideation, but not alcohol use or pain symptoms.
Conclusions
Early‐life unpredictability is an independent and consistent predictor of specific adult psychiatric symptoms, providing impetus for studying mechanisms of its effects on the developing brain that promote risk for psychopathology.
The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of ...intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n = 15 sham and n = 15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in the nVNS group (p < .0005) bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Studies of bipolar disorder (BD) suggest a genetic basis of the illness that alters brain function and morphology. In recent years, a number of genetic variants associated with BD have been ...identified. However, little is known about the associated genes, or brain circuits that rely upon their function. Using an anatomically comprehensive survey of the human transcriptome (The Allen Brain Atlas), we mapped the expression of 58 genes with suspected involvement in BD based upon their relationship to SNPs identified in genome wide association studies (GWAS). We then conducted a meta-analysis of structural MRI studies to identify brain regions that are abnormal in BD. Of 58 BD associated genes, 22 had anatomically distinct expression patterns that could be categorized into one of three clusters (C1-C3). Brain regions with the highest and lowest expression of these genes did not overlap strongly with anatomical sites identified as abnormal by structural MRI except in the parahippocampal gyrus, the inferior/superior temporal gyrus and the cerebellar vermis, regions where overlap was significant. Using the 22 genes in C1-C3 as reference points, additional genes with correlated expression patterns were identified and organized into sets based on similarity. Further analysis revealed that five of these gene sets were significantly associated with BD, suggesting that anatomical expression profile is correlated with genetic susceptibility to BD, particularly for genes in C2. Our data suggest that expression profiles of BD-associated genes do not explain the majority of structural abnormalities observed in BD, but may be useful in identifying new candidate genes. Our results highlight the complex neuroanatomical basis of BD, and reinforce illness models that emphasize impaired brain connectivity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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