Kundalini Yoga Intervention Increases Hippocampal Volume in Older Adults: A Pilot Randomized Controlled Trial.

Background: Among a rapidly aging population, there is increased need for neuroprotective interventions promoting healthy neurological aging. Mind-body interventions, such as Kundalini yoga, are actively being explored as accessible means to encourage healthy aging. However, little remains known about the neurobiological effects of Kundalini yoga. Aims: This pilot randomized-controlled trial (RCT) examined the potential neuroprotective effects of Kundalini yoga in older adults. Methods: We conducted an RCT with 11 healthy meditation-naïve older adults. Participants were randomized to a Kundalini yoga or psychoeducation intervention. Structural magnetic resonance imaging data were obtained at baseline and 12-week follow-up. The primary outcome measure was gray matter volume of the bilateral hippocampi and bilateral posterior cingulate cortex. Results: We found significant right hippocampal volume increases specific to the Kundalini yoga group (P = 0.034, ηp 2 = 0.408). Conclusions: These findings provide initial neurobiological support for the neuroprotective effects of Kundalini yoga.

Underuse of recommended treatments among people living with treatment-resistant psychosis.

Background: International guidelines recommend that individuals with treatment-resistant psychosis must be treated with clozapine. ECT has also been reported to improve symptom profiles. Identification of clozapine and/or ECT use in real-world practice enables understanding of the extent to which this evidence-base is implemented. Setting: Statewide public health tertiary referral service, the Tertiary Referral Service for Psychosis (TRSP), NSW, Australia. Objectives: To (i) describe clinical characteristics of individuals with treatment-resistant psychosis and to detail the proportion who had received a trial of clozapine or ECT at any point during their illness course; (ii) describe the characteristics of the treatment trials in both those currently on clozapine and those previously on clozapine; (iii) document reasons in relevant individuals why clozapine had never been used. Methods: All TRSP clients who met the criteria for treatment resistance (TR) were included. A detailed casenote review was conducted to examine whether clozapine and/or ECT had ever been prescribed. Characteristics of clozapine and ECT trials were documented. Tertiary service treatment recommendations are described. Findings: Thirty-six of 48 individuals had TR. They had marked clinical and functional impairment. A minority were currently receiving clozapine (n = 14/36). Most had received a clozapine trial at some point (n = 32/36). Most experienced persistent clinical symptoms while on clozapine (n = 29/32). Clozapine plasma levels were very rarely reported (4/32). Augmentation and antipsychotic polypharmacy were common among those currently on clozapine. The median clozapine trial duration was 4.0 (IQR: 3.0-20.3) months in individuals previously prescribed clozapine. Reasons for clozapine discontinuation included intolerable side effects (n = 10/18) and poor adherence (n = 7/18). One-quarter of TR individuals had trialed ECT (n = 9/36). Tertiary service recommendations included routine plasma monitoring to optimize dose among people currently on clozapine; clozapine retrial in those previously treated; and clozapine initiation for those who had never received clozapine. ECT was recommended to augment clozapine and as an alternative where clozapine trial/retrial was not feasible. Conclusion: Among people with TR referred to a tertiary service, clozapine and ECT were underutilized. Clozapine trials are typically terminated without an adequate trial. Strategies to optimize the use of clozapine therapy and ECT in clinical settings are needed to increase the therapeutic effectiveness of evidence-based therapies for treatment-resistant psychosis.

Understanding the effects of serotonin in the brain through its role in the gastrointestinal tract.

The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function and cognitive capacities as diverse as reward processing, exploration, and the psychedelic experience, over 95% of the serotonin in the body is released in the gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural serotonin as a rostral extension of the gastrointestinal serotonergic system dissolves much of the mystery associated with the central serotonergic system. Specifically, we outline that central serotonin activity mimics the effects of a digestion/satiety circuit mediated by hypothalamic control over descending serotonergic nuclei in the brainstem. We review commonalities and differences between these two circuits, with a focus on the heterogeneous expression of different classes of serotonin receptors in the brain. Much in the way that serotonin-induced peristalsis facilitates the work of digestion, serotonergic influences over cognition can be reframed as performing the work of cognition. Extending this analogy, we argue that the central serotonergic system allows the brain to arbitrate between different cognitive modes as a function of serotonergic tone: low activity facilitates cognitive automaticity, whereas higher activity helps to identify flexible solutions to problems, particularly if and when the initial responses fail. This perspective sheds light on otherwise disparate capacities mediated by serotonin, and also helps to understand why there are such pervasive links between serotonergic pathology and the symptoms of psychiatric disorders.

Neuromodulation of the mind-wandering brain state: the interaction between neuromodulatory tone, sharp wave-ripples and spontaneous thought.

Mind-wandering has become a captivating topic for cognitive neuroscientists. By now, it is reasonably well described in terms of its phenomenology and the large-scale neural networks that support it. However, we know very little about what neurobiological mechanisms trigger a mind-wandering episode and sustain the mind-wandering brain state. Here, we focus on the role of ascending neuromodulatory systems (i.e. acetylcholine, noradrenaline, serotonin and dopamine) in shaping mind-wandering. We advance the hypothesis that the hippocampal sharp wave-ripple (SWR) is a compelling candidate for a brain state that can trigger mind-wandering episodes. This hippocampal rhythm, which occurs spontaneously in quiescent behavioural states, is capable of propagating widespread activity in the default network and is functionally associated with recollective, associative, imagination and simulation processes. The occurrence of the SWR is heavily dependent on hippocampal neuromodulatory tone. We describe how the interplay of neuromodulators may promote the hippocampal SWR and trigger mind-wandering episodes. We then identify the global neuromodulatory signatures that shape the evolution of the mind-wandering brain state. Under our proposed framework, mind-wandering emerges due to the interplay between neuromodulatory systems that influence the transitions between brain states, which either facilitate, or impede, a wandering mind. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.

Mind-wandering in Parkinson's disease hallucinations reflects primary visual and default network coupling.

Visual hallucinations are an underappreciated symptom affecting the majority of patients during the natural history of Parkinson's disease. Little is known about other forms of abstract and internally generated cognition - such as mind-wandering - in this population, but emerging evidence suggests that an interplay between the brain's primary visual and default networks might play a crucial role in both internally generated imagery and hallucinations. Here, we explored the association between mind-wandering and visual hallucinations in Parkinson's disease, and their relationship with brain network coupling. We administered a validated thought-sampling task to 38 Parkinson's disease patients (18 with hallucinations; 20 without) and 40 controls, to test the hypothesis that individuals with hallucinations experience an increased frequency of mind-wandering. Group differences in the association between mind-wandering frequency and brain network coupling were also examined using resting state functional magnetic resonance imaging. Our results showed that patients with hallucinations exhibited significantly higher mind-wandering frequencies compared to non-hallucinators, who in turn had reduced levels of mind-wandering relative to controls. At the level of brain networks, inter-network connectivity and seed-to-voxel analyses identified that increased mind-wandering in the hallucinating versus non-hallucinating group was associated with greater coupling between the primary visual cortex and dorsal default network. Taken together, our results suggest a relative preservation of mind-wandering in Parkinson's disease patients who experience visual hallucinations, which is associated with increased visual cortex-default network coupling. We propose that the preservation of florid abstract and internally generated cognition in the context of the Parkinson's disease can contribute to visual hallucinations, whereas healthy individuals experience only the vivid images of the mind's eye. These findings refine current models of visual hallucinations by identifying a specific cognitive phenomenon and neural substrate consistent with the top-down influences over perception that have been implicated in hallucinations across neuropsychiatric disorders.

Anosognosia predicts default mode network hypometabolism and clinical progression to dementia.

OBJECTIVE: To identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment. METHODS: We stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline ß-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia. RESULTS: We found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame. CONCLUSIONS: Our results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

Altered Insula Connectivity under MDMA.

Recent work with noninvasive human brain imaging has started to investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA) on large-scale patterns of brain activity. MDMA, a potent monoamine-releaser with particularly pronounced serotonin- releasing properties, has unique subjective effects that include: marked positive mood, pleasant/unusual bodily sensations and pro-social, empathic feelings. However, the neurobiological basis for these effects is not properly understood, and the present analysis sought to address this knowledge gap. To do this, we administered MDMA-HCl (100 mg p.o.) and, separately, placebo (ascorbic acid) in a randomized, double-blind, repeated-measures design with twenty-five healthy volunteers undergoing fMRI scanning. We then employed a measure of global resting-state functional brain connectivity and follow-up seed-to-voxel analysis to the fMRI data we acquired. Results revealed decreased right insula/salience network functional connectivity under MDMA. Furthermore, these decreases in right insula/salience network connectivity correlated with baseline trait anxiety and acute experiences of altered bodily sensations under MDMA. The present findings highlight insular disintegration (ie, compromised salience network membership) as a neurobiological signature of the MDMA experience, and relate this brain effect to trait anxiety and acutely altered bodily sensations-both of which are known to be associated with insular functioning.

Visual Hallucinations Are Characterized by Impaired Sensory Evidence Accumulation: Insights From Hierarchical Drift Diffusion Modeling in Parkinson's Disease.

BACKGROUND: Models of hallucinations emphasize imbalance between sensory input and top-down influences over perception, as false perceptual inference can arise when top-down predictions are afforded too much precision (certainty) relative to sensory evidence. Visual hallucinations in Parkinson's disease (PD) are associated with lower-level visual and attentional impairments, accompanied by overactivity in higher-order association brain networks. PD therefore provides an attractive framework to explore contributions of bottom-up versus top-down disturbances in hallucinations. METHODS: We characterized sensory processing during perceptual decision making in patients with PD with (n = 20) and without (n = 25) visual hallucinations and control subjects (n = 12), by fitting a hierarchical drift diffusion model to an attentional task. The hierarchical drift diffusion model uses Bayesian estimates to decompose task performance into parameters reflecting drift rates of evidence accumulation, decision thresholds, and nondecision time. RESULTS: We observed slower drift rates in patients with hallucinations, which were less sensitive to changes in task demand. In contrast, wider decision boundaries and shorter nondecision times relative to control subjects were found in patients with PD regardless of hallucinator status. Inefficient and less flexible sensory evidence accumulation emerges as a unique feature of PD hallucinators. CONCLUSIONS: We integrate these results with evidence accumulation and predictive coding models of hallucinations, suggesting that in PD sensory evidence is less informative and may therefore be down-weighted, resulting in overreliance on top-down influences. Considering impaired drift rates as an approximation of reduced sensory precision, our findings provide a novel computational framework to specify impairments in sensory processing that contribute to development of visual hallucinations.