The (In)flexible self: Psychopathology, mindfulness, and neuroscience

Clinical and neuroscientific evidence indicates that transdiagnostic processes contribute to the generation and maintenance of psychopathological symptoms and disorders. Rigidity (inflexibility) appears a core feature of most transdiagnostic pathological processes. Decreasing rigidity may prove important to restore and maintain mental health. One of the primary domains in which rigidity and flexibility plays a role concerns the self. We adopt the pattern theory of self (PTS) for a working definition of self. This incorporates the pluralist view on self as constituted by multiple aspects or processes, understood to constitute a self-pattern, i.e. processes organized in non-linear dynamical relations across a number of time scales. The use of mindfulness meditation in the format of Mindfulness Based Interventions (MBIs) has been developed over four decades in Clinical Psychology. MBIs are promising as evidence-based treatments, shown to be equivalent to gold-standard treatments and superior to specific active controls in several randomized controlled trials. Notably, MBIs have been shown to target transdiagnostic symptoms. Given the hypothesized central role of rigid, habitual self-patterns in psychopathology, PTS offers a useful frame to understand how mindfulness may be beneficial in decreasing inflexibility. We discuss the evidence that mindfulness can alter the psychological and behavioral expression of individual aspects of the self-pattern, as well as favour change in the self-pattern as a whole gestalt. We discuss neuroscientific research on how the phenomenology of the self (pattern) is reflected in associated cortical networks and meditation-related alterations in cortical networks. Creating a synergy between these two aspects can increase understanding of psychopathological processes and improve diagnostic and therapeutic options. (AU)

Cessations of consciousness in meditation: Advancing a scientific understanding of nirodha samapatti.

Absence of consciousness can occur due to a concussion, anesthetization, intoxication, epileptic seizure, or other fainting/syncope episode caused by lack of blood flow to the brain. However, some meditation practitioners also report that it is possible to undergo a total absence of consciousness during meditation, lasting up to 7 days, and that these "cessations" can be consistently induced. One form of extended cessation (i.e., nirodha samapatti) is thought to be different from sleep because practitioners are said to be completely impervious to external stimulation. That is, they cannot be 'woken up' from the cessation state as one might be from a dream. Cessations are also associated with the absence of any time experience or tiredness, and are said to involve a stiff rather than a relaxed body. Emergence from meditation-induced cessations is said to have profound effects on subsequent cognition and experience (e.g., resulting in a sudden sense of clarity, openness, and possibly insights). In this paper, we briefly outline the historical context for cessation events, present preliminary data from two labs, set a research agenda for their study, and provide an initial framework for understanding what meditation induced cessation may reveal about the mind and brain. We conclude by integrating these so-called nirodha and nirodha samapatti experiences-as they are known in classical Buddhism-into current cognitive-neurocomputational and active inference frameworks of meditation.

The (In)flexible self: Psychopathology, mindfulness, and neuroscience.

Clinical and neuroscientific evidence indicates that transdiagnostic processes contribute to the generation and maintenance of psychopathological symptoms and disorders. Rigidity (inflexibility) appears a core feature of most transdiagnostic pathological processes. Decreasing rigidity may prove important to restore and maintain mental health. One of the primary domains in which rigidity and flexibility plays a role concerns the self. We adopt the pattern theory of self (PTS) for a working definition of self. This incorporates the pluralist view on self as constituted by multiple aspects or processes, understood to constitute a self-pattern, i.e. processes organized in non-linear dynamical relations across a number of time scales. The use of mindfulness meditation in the format of Mindfulness Based Interventions (MBIs) has been developed over four decades in Clinical Psychology. MBIs are promising as evidence-based treatments, shown to be equivalent to gold-standard treatments and superior to specific active controls in several randomized controlled trials. Notably, MBIs have been shown to target transdiagnostic symptoms. Given the hypothesized central role of rigid, habitual self-patterns in psychopathology, PTS offers a useful frame to understand how mindfulness may be beneficial in decreasing inflexibility. We discuss the evidence that mindfulness can alter the psychological and behavioral expression of individual aspects of the self-pattern, as well as favour change in the self-pattern as a whole gestalt. We discuss neuroscientific research on how the phenomenology of the self (pattern) is reflected in associated cortical networks and meditation-related alterations in cortical networks. Creating a synergy between these two aspects can increase understanding of psychopathological processes and improve diagnostic and therapeutic options.

The effects of beta-endorphin: state change modification.

Beta-endorphin (ß-END) is an opioid neuropeptide which has an important role in the development of hypotheses concerning the non-synaptic or paracrine communication of brain messages. This kind of communication between neurons has been designated volume transmission (VT) to differentiate it clearly from synaptic communication. VT occurs over short as well as long distances via the extracellular space in the brain, as well as via the cerebrospinal fluid (CSF) flowing through the ventricular spaces inside the brain and the arachnoid space surrounding the central nervous system (CNS). To understand how ß-END can have specific behavioral effects, we use the notion behavioral state, inspired by the concept of machine state, coming from Turing (Proc London Math Soc, Series 2,42:230-265, 1937). In section 1.4 the sequential organization of male rat behavior is explained showing that an animal is not free to switch into another state at any given moment. Funneling-constraints restrict the number of possible behavioral transitions in specific phases while at other moments in the sequence the transition to other behavioral states is almost completely open. The effects of ß-END on behaviors like food intake and sexual behavior, and the mechanisms involved in reward, meditation and pain control are discussed in detail. The effects on the sequential organization of behavior and on state transitions dominate the description of these effects.

Metacognitive awareness of covert somatosensory attention corresponds to contralateral alpha power.

Studies on metacognition have shown that participants can report on their performance on a wide range of perceptual, memory and behavioral tasks. We know little, however, about the ability to report on one's attentional focus. The degree and direction of somatosensory attention can, however, be readily discerned through suppression of alpha band frequencies in EEG/MEG produced by the somatosensory cortex. Such top-down attentional modulations of cortical excitability have been shown to result in better discrimination performance and decreased response times. In this study we asked whether the degree of attentional focus is also accessible for subjective report, and whether such evaluations correspond to the amount of somatosensory alpha activity. In response to auditory cues participants maintained somatosensory attention to either their left or right hand for intervals varying randomly between 5 and 32 seconds, while their brain activity was recorded with MEG. Trials were terminated by a probe sound, to which they reported their level of attention on the cued hand right before probe-onset. Using a beamformer approach, we quantified the alpha activity in left and right somatosensory regions, one second before the probe. Alpha activity from contra- and ipsilateral somatosensory cortices for high versus low attention trials were compared. As predicted, the contralateral somatosensory alpha depression correlated with higher reported attentional focus. Finally, alpha activity two to three seconds before the probe-onset was correlated with attentional focus. We conclude that somatosensory attention is indeed accessible to metacognitive awareness.

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.

Mindfulness reduces habitual responding based on implicit knowledge: evidence from artificial grammar learning.

Participants were unknowingly exposed to complex regularities in a working memory task. The existence of implicit knowledge was subsequently inferred from a preference for stimuli with similar grammatical regularities. Several affective traits have been shown to influence AGL performance positively, many of which are related to a tendency for automatic responding. We therefore tested whether the mindfulness trait predicted a reduction of grammatically congruent preferences, and used emotional primes to explore the influence of affect. Mindfulness was shown to correlate negatively with grammatically congruent responses. Negative primes were shown to result in faster and more negative evaluations. We conclude that grammatically congruent preference ratings rely on habitual responses, and that our findings provide empirical evidence for the non-reactive disposition of the mindfulness trait.

Volume transmission of beta-endorphin via the cerebrospinal fluid; a review.

There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ß-endorphin (ß-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ß-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ß-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ß-END, independence of peripheral versus central levels, central ß-END migration over considerable distances, behavioral effects of ß-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain.

Sensorimotor Alpha Activity is Modulated in Response to the Observation of Pain in Others.

The perception-action account of empathy states that observation of another person's state automatically activates a similar state in the observer. It is still unclear in what way ongoing sensorimotor alpha oscillations are involved in this process. Although they have been repeatedly implicated in (biological) action observation and understanding communicative gestures, less is known about their role in vicarious pain observation. Their role is understood as providing a graded inhibition through functional inhibition, thereby streamlining information flow through the cortex. Although alpha oscillations have been shown to have at least visual and sensorimotor origins, only the latter are expected to be involved in the empathetic response. Here, we used magnetoencephalography, allowing us to spatially distinguish and localize oscillatory components using beamformer source reconstruction. Subjects observed realistic pictures of limbs in painful and no-pain (control) conditions. As predicted, time-frequency analysis indeed showed increased alpha suppression in the pain condition compared to the no-pain condition. Although both pain and no-pain conditions suppressed alpha- and beta-band activity at both posterior and central sensors, the pain condition suppressed alpha more only at central sensors. Source reconstruction localized these differences along the central sulcus. Our results could not be accounted for by differences in the evoked fields, suggesting a unique role of oscillatory activity in empathetic responses. We argue that alpha oscillations provide a unique measure of the underlying functional architecture of the brain, suggesting an automatic disinhibition of the sensorimotor cortices in response to the observation of pain in others.

On the Relationship Between the Practice of Mindfulness Meditation and Personality-an Exploratory Analysis of the Mediating Role of Mindfulness Skills.

Mindfulness meditation (MM) has often been suggested to induce fundamental changes in the way events in life are experienced and dealt with, presumably leading to alterations in personality. However, the relationship between the practice of MM and personality has not been systematically studied. The aim of this study was to explore this relationship and to investigate the mediating role of mindfulness skills. Thirty-five experienced mindfulness meditators (age range, 31-75 years; meditation experience range, 0.25-35 years; mean, ∼13 years) and 35 age-, gender-, and ethnicity-matched controls (age range, 27-63 years) without any meditation experience completed a personality (NEO-FFI) and mindfulness (KIMS) questionnaire. The practice of MM was positively related to openness and extraversion and negatively related to neuroticism and conscientiousness. Thus, the results of the current study associate the practice of MM with higher levels of curiosity and receptivity to new experiences and experience of positive affect and with less proneness toward negative emotions and worrying and a reduced focus on achievements. Furthermore, the mediating role of specific mindfulness skills in the relationship between the practice of MM and personality traits was shown.

Mindfulness meditation associated with alterations in bottom-up processing: psychophysiological evidence for reduced reactivity.

Mental training by meditation has been related to changes in high-level cognitive functions that involve top-down processing. The aim of this study was to investigate whether the practice of meditation is also related to alterations in low-level, bottom-up processing. Therefore, intersensory facilitation (IF) effects in a group of mindfulness meditators (MM) were compared to IF effects in an age- and gender-matched control group. Smaller and even absent IF effects were found in the MM group, which suggests that changes in bottom-up processing are associated with MM. Furthermore, reduced interference of a visual warning stimulus with the IF effects was found, which suggests an improved allocation of attentional resources in mindfulness meditators, even across modalities.

Oxytocin-messages via the cerebrospinal fluid: behavioral effects; a review.

The cerebrospinal fluid (CSF) usually is considered as a protective 'nutrient and waste control' system for the brain. Recent findings suggest, however, that the composition of CSF is actively controlled and may play an influential role in the changes in brain activity, underlying different behavioral states. In the present review, we present an overview of available data concerning the release of oxytocin into the CSF, the location of the oxytocin-receptive brain areas and the behavioral effects of intracerebroventricular oxytocin. About 80% of the oxytocin-receptive areas are located close to the ventricular or subarachnoid CSF, including the hypothalamic 'Behavior Control Column' (L.W.Swanson, 2003). As a conclusion we suggest that 'CSF-oxytocin' contributes considerably to the non-synaptic communication processes involved in hypothalamic-, brainstem- and olfactory brain areas and behavioral states and that the flowing CSF is used as a 'broadcasting system' to send coordinated messages to a wide variety of nearby and distant brain areas.

Greater efficiency in attentional processing related to mindfulness meditation.

In this study, attentional processing in relation to mindfulness meditation was investigated. Since recent studies have suggested that mindfulness meditation may induce improvements in attentional processing, we have tested 20 expert mindfulness meditators in the attention network test. Their performance was compared to that of 20 age- and gender-matched controls. In addition to attentional network analyses, overall attentional processing was analysed by means of efficiency scores (i.e., accuracy controlled for reaction time). Better orienting and executive attention (reflected by smaller differences in either reaction time or error score, respectively) were observed in the mindfulness meditation group. Furthermore, extensive mindfulness meditation appeared to be related to a reduction of the fraction of errors for responses with the same reaction time. These results provide new insights into differences in attentional processing related to mindfulness meditation and suggest the possibility of increasing the efficiency in attentional processing by extensive mental training.

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review.

The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states.

Brain distribution and evidence for both central and neurohormonal actions of cocaine- and amphetamine-regulated transcript peptide in Xenopus laevis.

We tested the hypothesis that, in the amphibian Xenopus laevis, cocaine- and amphetamine-regulated transcript peptide (CARTp) not only has widespread actions in the brain but also acts as a local factor in endocrine pituitary cells and/or is neurohemally secreted into the circulation to control peripheral targets. CARTp-immunoreactive cells occur in the olfactory bulb, nucleus accumbens, amygdala, septum, striatum, nucleus of Bellonci, ventrolateral nucleus, central thalamic nucleus, preoptic nuclei, and suprachiasmatic nucleus, and particularly in the medial pallium, ventromedial nucleus, hypothalamus, Edinger-Westphal nucleus, optic tectum, raphe nuclei, central gray, nucleus of the solitary tract, and spinal cord. From the hypothalamic magnocellular nucleus, CARTp-containing axons run to the neurohemal median eminence, and to the neural pituitary lobe to form neurohemal terminals, as shown by immunoelectron microscopy. Starvation increases the number of CARTp-cells in the optic tectum by 46% but has no effect on such cells in the torus semicircularis. CARTp does not affect in vitro release of alpha-melanophore-stimulating hormone from pituitary melanotrope cells. Our results support the hypothesis that in X. laevis, CARTp not only has multiple and not exclusively feeding-related actions in the brain but is also secreted as a neurohormone 1) into the portal system to control endocrine targets in the pituitary distal lobe and 2) from neurohemal axon terminals in the neural pituitary lobe to act peripherally. The differences in CARTp distribution between X. laevis and Rana esculenta may be related to different environmental and physiological conditions such as feeding, sensory information processing, and locomotion.

The challenge of computer mathematics.

Progress in the foundations of mathematics has made it possible to formulate all thinkable mathematical concepts, algorithms and proofs in one language and in an impeccable way. This is not in spite of, but partially based on the famous results of Gödel and Turing. In this way statements are about mathematical objects and algorithms, proofs show the correctness of statements and computations, and computations are dealing with objects and proofs. Interactive computer systems for a full integration of defining, computing and proving are based on this. The human defines concepts, constructs algorithms and provides proofs, while the machine checks that the definitions are well formed and the proofs and computations are correct. Results formalized so far demonstrate the feasibility of this 'computer mathematics'. Also there are very good applications. The challenge is to make the systems more mathematician-friendly, by building libraries and tools. The eventual goal is to help humans to learn, develop, communicate, referee and apply mathematics.

Opioid peptides, CRF, and urocortin in cerebrospinal fluid-contacting neurons in Xenopus laevis.

The presence of the opioids, beta-endorphin, met-enkephalin, and endomorphin, and of corticotropin-releasing factor (CRF) and the CRF family member, urocortin (Ucn), is described in cerebrospinal fluid-contacting neurons in the brain of the amphibian, Xenopus laevis.

Evidence that urocortin I acts as a neurohormone to stimulate alpha MSH release in the toad Xenopus laevis.

We have raised the hypothesis that in the South African clawed toad Xenopus laevis, urocortin 1 (UCN1), a member of the corticotropin-releasing factor (CRF) peptide family, functions not only within the brain as a neurotransmitter/neuromodulator but also as a neurohormone, promoting the release of alpha-melanophore-stimulating hormone (alphaMSH) from the neuroendocrine melanotrope cells in the intermediate lobe of the pituitary gland. This hypothesis has been investigated by (1) assessing the distribution of UCN1 and CRF by light immunocytochemistry, (2) determining the subcellular presence of UCN1 in the neural lobe of the pituitary gland by immuno-electron microscopy applying high-pressure freezing and cryosubstitution, and (3) testing the effect of UCN1 on MSH release from toad melanotrope cells using in vitro superfusion. In the X. laevis brain, the main site of UCN1-positive somata was found to be the Edinger-Westphal nucleus. UCN1 immunoreactivity (ir) also occurs in the nucleus posteroventralis tegmenti, central gray, nucleus reticularis medius, nucleus motorius nervi facialis, and nucleus motorius nervi vagi. UCN1 occurs together with CRF in the nucleus motorius nervi trigemini, and in the magnocellular nucleus, which send a UCN1- and CRF-containing fiber tract to the median eminence. Strong UCN1-ir and CRF-ir were found in the external zone of the median eminence. From the internal zone of the median eminence, UCN1-ir fibers, but few CRF-ir fibers, were found to project to the pituitary neural lobe, where they form numerous neurohemal axon terminals. Ultrastructurally, two types of terminal containing UCN1-ir secretory granules were distinguished: type A contains large, moderately electron-dense, round secretory granules and type B is filled with smaller, strongly electron-dense, ellipsoid secretory granules. In vitro superfusion studies showed that UCN1 stimulated the release of alphaMSH from melanotrope cells in a dose-dependent manner. Our results support the hypothesis that in X. laevis, UCN1 released from neurohemal axon terminals in the pituitary neural lobe functions as a stimulatory neurohormone for alphaMSH release from melanotrope cells of the pituitary intermediate lobe.