Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Linear and Nonlinear EEG-Based Functional Networks in Anxiety Disorders.

Electrocortical network dynamics are integral to brain function. Linear and nonlinear connectivity applications enrich neurophysiological investigations into anxiety disorders. Discrete EEG-based connectivity networks are unfolding with some homogeneity for anxiety disorder subtypes. Attenuated delta/theta/beta connectivity networks, pertaining to anterior-posterior nodes, characterize panic disorder. Nonlinear measures suggest reduced connectivity of ACC as an executive neuro-regulator in germane "fear circuitry networks" might be more central than considered. Enhanced network complexity and theta network efficiency at rest define generalized anxiety disorder, with similar tonic hyperexcitability apparent in social anxiety disorder further extending to task-related/state functioning. Dysregulated alpha connectivity and integration of mPFC-ACC/mPFC-PCC relays implicated with attentional flexibility and choice execution/congruence neurocircuitry are observed in trait anxiety. Conversely, state anxiety appears to recruit converging delta and beta connectivity networks as panic, suggesting trait and state anxiety are modulated by discrete neurobiological mechanisms. Furthermore, EEG connectivity dynamics distinguish anxiety from depression, despite prevalent clinical comorbidity. Rethinking mechanisms implicated in the etiology, maintenance, and treatment of anxiety from the perspective of EEG network science across micro- and macroscales serves to shed light and move the field forward.

The Efficacy of Adapted MBCT on Core Symptoms and Executive Functioning in Adults With ADHD: A Preliminary Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to examine the effectiveness of mindfulness as a treatment for adults diagnosed with ADHD. A 12-week-adapted mindfulness-based cognitive therapy (MBCT) program is compared with a waiting list (WL) group. METHOD: Adults with ADHD were randomly allocated to MBCT ( n = 55) or waitlist ( n = 48). Outcome measures included investigator-rated ADHD symptoms (primary), self-reported ADHD symptoms, executive functioning, depressive and anxiety symptoms, patient functioning, and mindfulness skills. RESULTS: MBCT resulted in a significant reduction of ADHD symptoms, both investigator-rated and self-reported, based on per-protocol and intention-to-treat analyses. Significant improvements in executive functioning and mindfulness skills were found. Additional analyses suggested that the efficacy of MBCT in reducing ADHD symptoms and improving executive functioning is partially mediated by an increase in the mindfulness skill "Act With Awareness." No improvements were observed for depressive and anxiety symptoms, and patient functioning. CONCLUSION: This study provides preliminary support for the effectiveness of MBCT for adults with ADHD.

Mapping complex mind states: EEG neural substrates of meditative unified compassionate awareness.

Specific mental training cultivates diminished self-reference, encompassing non-duality, emptiness, awakened-awareness, and compassionate experiences. We aimed to elucidate the neural substrates of four distinct, interdependent Essence-of-Mind states: (1) timelessness, (2) non-preference, non-duality, non-conceptualization, (3) the view of luminosity and limitlessness, (4) unified compassionate experience of oneness (stable awakened-awareness). EEG data were collected from 30 advanced meditators concomitant to eyes-open/eyes-closed resting baseline, followed by 60-min of instructed practice. Alpha, beta, and gamma, frequency-spatial EEG-dimensions were analyzed. The results revealed that compared to baseline, current density across frequencies significantly decreased upon meditation onset in self-referential, and executive-control regions. During meditation, gamma-band current density significantly increased from state-1 compared to state-4, within the ACC, precuneus, and superior parietal lobule, whereas beta-band activity increased within the insula. These findings suggest a dissociation between brain regions regulating self-referential vs. executive-control processing, during non-dual, compassionate states, characterized by brilliantly awake awareness, free from conceptual thought and "doing".

Multi-dimensional modulations of α and γ cortical dynamics following mindfulness-based cognitive therapy in Major Depressive Disorder.

To illuminate candidate neural working mechanisms of Mindfulness-Based Cognitive Therapy (MBCT) in the treatment of recurrent depressive disorder, parallel to the potential interplays between modulations in electro-cortical dynamics and depressive symptom severity and self-compassionate experience. Linear and nonlinear α and γ EEG oscillatory dynamics were examined concomitant to an affective Go/NoGo paradigm, pre-to-post MBCT or natural wait-list, in 51 recurrent depressive patients. Specific EEG variables investigated were; (1) induced event-related (de-) synchronisation (ERD/ERS), (2) evoked power, and (3) inter-/intra-hemispheric coherence. Secondary clinical measures included depressive severity and experiences of self-compassion. MBCT significantly downregulated α and γ power, reflecting increased cortical excitability. Enhanced α-desynchronisation/ERD was observed for negative material opposed to attenuated α-ERD towards positively valenced stimuli, suggesting activation of neural networks usually hypoactive in depression, related to positive emotion regulation. MBCT-related increase in left-intra-hemispheric α-coherence of the fronto-parietal circuit aligned with these synchronisation dynamics. Ameliorated depressive severity and increased self-compassionate experience pre-to-post MBCT correlated with α-ERD change. The multi-dimensional neural mechanisms of MBCT pertain to task-specific linear and non-linear neural synchronisation and connectivity network dynamics. We propose MBCT-related modulations in differing cortical oscillatory bands have discrete excitatory (enacting positive emotionality) and inhibitory (disengaging from negative material) effects, where mediation in the α and γ bands relates to the former.

Modulation of induced frontocentral theta (Fm-θ) event-related (de-)synchronisation dynamics following mindfulness-based cognitive therapy in Major Depressive Disorder.

Depressive severity has been associated with attenuated neocortical frontal midline theta (Fm-θ) power/evoked activity. Mindfulness-Based Cognitive Therapy (MBCT) has shown to be a successful novel intervention for Major Depressive Disorder (MDD), albeit precise working mechanisms remain elusive. We examined the hypothesis that MBCT would have modulating effects upon evoked Fm-θ power, in addition to investigating possible mediation of induced event-related de/synchronisation (ERD/ERS) dynamics. Fifty one patients with a primary diagnosis of MDD (26 exposed to MBCT vs. 25 wait-list/WL controls) undertook a Go/NoGo task consisting of positive, negative and neutral words, further stratified into abstract versus trait adjective matrices. Depressive symptom severity and rumination were also examined. A pattern of enhanced induced Fm-θ synchronisation during the latter 400-800 ms temporal-window pre-to-post MBCT was observed; the contrary in the WL. Modulated ERD/ERS dynamics correlated to amelioration in depressive and rumination symptoms in the MBCT group. We propose the primary action pathway alluded to a neural disengagement mechanism enacting upon tonic neuronal assemblies implicated in emotional and self-related processing. Due to the complexity and presently undiscovered complete unified scientific understanding of neuro-oscillatory-dynamics, and associated clinical interplays; we hypothesise that the electro-cortical and connected clinical working pathways of MBCT in depression are multi-levelled constituting nonlinear and interdependent mechanisms, represented by mediated EEG synchronisation dynamics.

Biofeedback for psychiatric disorders: a systematic review.

Biofeedback potentially provides non-invasive, effective psychophysiological interventions for psychiatric disorders. The encompassing purpose of this review was to establish how biofeedback interventions have been used to treat select psychiatric disorders [anxiety, autistic spectrum disorders, depression, dissociation, eating disorders, schizophrenia and psychoses] to date and provide a useful reference for consultation by clinicians and researchers planning to administer a biofeedback treatment. A systematic search of EMBASE, MEDLINE, PsycINFO, and WOK databases and hand searches in Applied Psychophysiology and Biofeedback, and Journal of Neurotherapy, identified 227 articles; 63 of which are included within this review. Electroencephalographic neurofeedback constituted the most investigated modality (31.7%). Anxiety disorders were the most commonly treated (68.3%). Multi-modal biofeedback appeared most effective in significantly ameliorating symptoms, suggesting that targeting more than one physiological modality for bio-regulation increases therapeutic efficacy. Overall, 80.9% of articles reported some level of clinical amelioration related to biofeedback exposure, 65.0% to a statistically significant (p < .05) level of symptom reduction based on reported standardized clinical parameters. Although the heterogeneity of the included studies warrants caution before explicit efficacy statements can be made. Further development of standardized controlled methodological protocols tailored for specific disorders and guidelines to generate comprehensive reports may contribute towards establishing the value of biofeedback interventions within mainstream psychiatry.

The error processing system in major depressive disorder: cortical phenotypal marker hypothesis.

Major depressive disorder (MDD) ensues reduced goal-directed cognition and behaviour. Cognitive and emotional flexibility to disengage and adapt future responses was examined in the error processing system (error-related negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed patients (21 current, 37 remitted) vs. 27 controls undergoing cognitive and affective Go/NoGo paradigms. ERN was equivalent between patient and controls for the cognitive task, albeit amplitude attenuated in patients during the affective task. Blunted ERN amplitudes were evident between patients and controls in males compared to females, plausibly underpinned by disparities in dopaminergic pathways. Patients displayed enhanced Pe amplitudes for both cognitive and affective tasks. Abberations in cortical error processing in MDD appear specific to affective systems for the pre-attentive ERN, opposed to cognitive and affective processing for the consciously-integrated Pe. Heightened Pe, observed in both current and remitted patients, advocates the possibility of the Pe waveform as a candidate intermediate phenotype of depression.

Effects of mindfulness-based cognitive therapy on neurophysiological correlates of performance monitoring in adult attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine whether mindfulness-based cognitive therapy (MBCT) would enhance attenuated amplitudes of event-related potentials (ERPs) indexing performance monitoring biomarkers of attention-deficit/hyperactivity disorder (ADHD). METHODS: Fifty adult ADHD patients took part in a randomised controlled study investigating ERP and clinical measures pre-to-post MBCT. Twenty-six patients were randomly allocated to MBCT, 24 to a wait-list control. Main outcome measures included error processing (ERN, Pe), conflict monitoring (NoGo-N2), and inhibitory control (NoGo-P3) ERPs concomitant to a continuous performance task (CPT-X). Inattention and hyperactivity-impulsivity ADHD symptoms, psychological distress and social functioning, and mindfulness skills were also assessed. RESULTS: MBCT was associated with increased Pe and NoGo-P3 amplitudes, coinciding with reduced 'hyperactivity/impulsivity' and 'inattention' symptomatology. Specific to the MBCT; enhanced Pe amplitudes correlated with a decrease in hyperactivity/impulsivity symptoms and increased 'act-with-awareness' mindfulness skill, whereas, enhanced P3 correlated with amelioration in inattention symptoms. CONCLUSIONS: MBCT enhanced ERP amplitudes associated with motivational saliency and error awareness, leading to improved inhibitory regulation. SIGNIFICANCE: MBCT suggests having comparable modulation on performance monitoring ERP amplitudes as pharmacological treatments. Further study and development of MBCT as a treatment for ADHD is warranted, in addition to its potential scope for clinical applicability to broader defined externalising disorders and clinical problems associated with impairments of the prefrontal cortex.

Psychophysiological investigations in depersonalization disorder and effects of electrodermal biofeedback.

Previous studies investigating depersonalization disorder (DPD) report a lower baseline skin conductance level (SCL) and attenuated skin conductance response (SCR) to emotive stimuli. We hypothesized that increasing physiological arousal levels via electrodermal biofeedback may ameliorate disembodiment and emotional numbing symptomatology. Real-time versus sham biofeedback yielded a significant SCL increase after just 3 real-time biofeedback sessions in healthy volunteers. Subsequently, a randomized controlled biofeedback trial was administered with DPD patients. Findings were not replicated as SCL tended to fall, curiously more substantially in the real-time condition, concomitant with increased low- and high-frequency heart rate variability. To further investigate abnormal autonomic regulation in DPD, we compared basal autonomic activity between patients and healthy volunteers and found the former to be significantly more labile, indexed by greater nonspecific SCRs and higher resting SCLs. Rather than low sympathetic arousal, DPD might be better characterized by abnormal autonomic regulation affecting emotional and physiological responsivity.

Error-related processing dysfunction in children aged 9 to 12 years presenting putative antecedents of schizophrenia.

BACKGROUND: Intervention aimed at preventing schizophrenia may be most effective if targeted at specific, but modifiable, functional impairments that present during childhood. We have developed a novel method of screening community samples aged 9 to 12 years to identify children who present a triad of putative antecedents of schizophrenia (ASz), defined as 1) speech and/or motor development lags/problems; 2) internalizing, externalizing, and/or peer-relationship problems in the clinical range; and 3) psychotic-like experiences. This study examined whether ASz children display brain function abnormalities during error processing that are similar to those exhibited by adults with schizophrenia. METHODS: Twenty-two ASz children and 26 typically developing (TD) children with no antecedents of schizophrenia completed an error-inducing Go/NoGo task during event-related potential recording. Group differences were examined in the amplitude and latency of four event-related potential components: the initial error-related negativity (ERN) and later error-positivity (Pe) elicited on false-alarm responses to NoGo trials, and the corresponding initial correct response negativity (CRN) and later correct response positivity (Pc) elicited during processing of correct responses to Go trials. RESULTS: Relative to TD children, ASz children were characterized by reduced ERN amplitude but unaffected CRN, Pe, and Pc amplitudes. No group differences were observed in the latency of any component. CONCLUSIONS: Children presenting a triad of putative antecedents of schizophrenia show error-processing dysfunction mimicking that observed in adults with schizophrenia using the same Go/NoGo paradigm. The ASz children displayed specific early error-processing deficits rather than a generalized deficit in self-monitoring.