Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation.

BACKGROUND: Pharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates. METHODS: To address this knowledge gap, we directly compared 2 pharmacological methods (psilocybin 0.2 mg/kg orally [n = 23] and lysergic acid diethylamide [LSD] 100 µg orally [n = 25]) and 2 nonpharmacological methods (hypnosis [n = 30] and meditation [n = 29]) using resting-state functional connectivity magnetic resonance imaging and assessed the predictive value of the data using a machine learning approach. RESULTS: We found that 1) no network reached significance in all 4 ASC methods; 2) pharmacological and nonpharmacological interventions of inducing ASCs showed distinct connectivity patterns that were predictive at the individual level; 3) hypnosis and meditation showed differences in functional connectivity when compared directly and also drove distinct differences when jointly compared with the pharmacological ASC interventions; and 4) psilocybin and LSD showed no differences in functional connectivity when directly compared with each other, but they did show distinct behavioral-neural relationships. CONCLUSIONS: Overall, these results extend our understanding of the mechanisms of action of ASCs and highlight the importance of exploring how these effects can be leveraged in the treatment of psychiatric disorders.

Self-regulation of the dopaminergic reward circuit in cocaine users with mental imagery and neurofeedback.

BACKGROUND: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here, we examined whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that obsessive and compulsive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN activity and tested if real-time fMRI (rtfMRI) neurofeedback (NFB) can improve self-regulation of the VTA/SN. METHODS: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with non-drug reward imagery alone, or combined with rtfMRI NFB. RESULTS: On a group level, HC and CU were able to activate the dopaminergic midbrain and other reward regions with reward imagery. In CU, the individual ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of reward imagery but did not result in transfer effects at the end of the session. CONCLUSION: CU can voluntary activate their reward system with non-drug reward imagery and improve this ability with rtfMRI NFB. Combining mental imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the use of rtfMRI NFB in the treatment of CUD.

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor.

Background: Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over studyduring which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps. Results: LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans. Conclusions: Together, these results strongly implicate the 5-HT2A receptor in LSD's neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD's mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics. Funding: Funded by the Swiss National Science Foundation, the Swiss Neuromatrix Foundation, the Usona Institute, the NIH, the NIAA, the NARSAD Independent Investigator Grant, the Yale CTSA grant, and the Slovenian Research Agency. Clinical trial number: NCT02451072

The psychedelic drug LSD alters thinking and perception. Users can experience hallucinations, in which they, for example, see things that are not there. Colors, sounds and objects can appear distorted, and time can seem to speed up or slow down. These changes bear some resemblance to the changes in thinking and perception that occur in certain psychiatric disorders, such as schizophrenia. Studying how LSD affects the brain could thus offer insights into the mechanisms underlying these conditions. There is also evidence that LSD itself could help to reduce the symptoms of depression and anxiety disorders. Preller et al. have now used brain imaging to explore the effects of LSD on the brains of healthy volunteers. This revealed that LSD reduced communication among brain areas involved in planning and decision-making, but it increased communication between areas involved in sensation and movement. Volunteers whose brains showed the most communication between sensory and movement areas also reported the strongest effects of LSD on their thinking and perception. Preller et al. also found that another drug called Ketanserin prevented LSD from altering how different brain regions communicate. It also prevented LSD from inducing changes in thinking and perception. Ketanserin blocks a protein called the serotonin 2A receptor, which is activated by a brain chemical called serotonin that, amongst other roles, helps to regulate mood. By mapping the location of the gene that produces the serotonin 2A receptor, Preller et al. showed that the receptor is present in brain regions that show altered communication after LSD intake, therefore pinpointing the importance of this receptor in the effects of LSD. Psychiatric disorders that produce psychotic symptoms affect vast numbers of people worldwide. Further research into how LSD affects the brain could help us to better understand how such symptoms arise, and may also lead to the development of more effective treatments for a range of mental health conditions.

Neural initialization of audiovisual integration in prereaders at varying risk for developmental dyslexia.

Learning letter-speech sound correspondences is a major step in reading acquisition and is severely impaired in children with dyslexia. Up to now, it remains largely unknown how quickly neural networks adopt specific functions during audiovisual integration of linguistic information when prereading children learn letter-speech sound correspondences. Here, we simulated the process of learning letter-speech sound correspondences in 20 prereading children (6.13-7.17 years) at varying risk for dyslexia by training artificial letter-speech sound correspondences within a single experimental session. Subsequently, we acquired simultaneously event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) scans during implicit audiovisual presentation of trained and untrained pairs. Audiovisual integration of trained pairs correlated with individual learning rates in right superior temporal, left inferior temporal, and bilateral parietal areas and with phonological awareness in left temporal areas. In correspondence, a differential left-lateralized parietooccipitotemporal ERP at 400 ms for trained pairs correlated with learning achievement and familial risk. Finally, a late (650 ms) posterior negativity indicating audiovisual congruency of trained pairs was associated with increased fMRI activation in the left occipital cortex. Taken together, a short (<30 min) letter-speech sound training initializes audiovisual integration in neural systems that are responsible for processing linguistic information in proficient readers. To conclude, the ability to learn grapheme-phoneme correspondences, the familial history of reading disability, and phonological awareness of prereading children account for the degree of audiovisual integration in a distributed brain network. Such findings on emerging linguistic audiovisual integration could allow for distinguishing between children with typical and atypical reading development. Hum Brain Mapp 38:1038-1055, 2017. © 2016 Wiley Periodicals, Inc.

Differential Neural Processing during Motor Imagery of Daily Activities in Chronic Low Back Pain Patients.

Chronic low back pain (chronic LBP) is both debilitating for patients but also a major burden on the health care system. Previous studies reported various maladaptive structural and functional changes among chronic LBP patients on spine- and supraspinal levels including behavioral alterations. However, evidence for cortical reorganization in the sensorimotor system of chronic LBP patients is scarce. Motor Imagery (MI) is suitable for investigating the cortical sensorimotor network as it serves as a proxy for motor execution. Our aim was to investigate differential MI-driven cortical processing in chronic LBP compared to healthy controls (HC) by means of functional magnetic resonance imaging (fMRI). Twenty-nine subjects (15 chronic LBP patients, 14 HC) were included in the current study. MI stimuli consisted of randomly presented video clips showing every-day activities involving different whole-body movements as well as walking on even ground and walking downstairs and upstairs. Guided by the video clips, subjects had to perform MI of these activities, subsequently rating the vividness of their MI performance. Brain activity analysis revealed that chronic LBP patients exhibited significantly reduced activity compared to HC subjects in MI-related brain regions, namely the left supplementary motor area and right superior temporal sulcus. Furthermore, psycho-physiological-interaction analysis yielded significantly enhanced functional connectivity (FC) between various MI-associated brain regions in chronic LBP patients indicating diffuse and non-specific changes in FC. Current results demonstrate initial findings about differences in MI-driven cortical processing in chronic LBP pointing towards reorganization processes in the sensorimotor network.

fMRI reveals lateralized pattern of brain activity modulated by the metrics of stimuli during auditory rhyme processing.

Our fMRI study investigates auditory rhyme processing in spoken language to further elucidate the topic of functional lateralization of language processing. During scanning, 14 subjects listened to four different types of versed word strings and subsequently performed either a rhyme or a meter detection task. Our results show lateralization to auditory-related temporal regions in the right hemisphere irrespective of task. As for the left hemisphere we report responses in the supramarginal gyrus as well as in the opercular part of the inferior frontal gyrus modulated by the presence of regular meter and rhyme. The interaction of rhyme and meter was associated with increased involvement of the superior temporal sulcus and the putamen of the right hemisphere. Overall, these findings support the notion of right-hemispheric specialization for suprasegmental analyses during processing of spoken sentences and provide neuroimaging evidence for the influence of metrics on auditory rhyme processing.

Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study.

The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders.