The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals.

A continuum hypothesis of psychotomimetic rapid antidepressants

Ketamine, classical psychedelics and sleep deprivation are associated with rapid effects on depression. Interestingly, these interventions also have common psychotomimetic actions, mirroring aspects of psychosis such as an altered sense of self, perceptual distortions and distorted thinking. This raises the question whether these interventions might be acute antidepressants through the same mechanisms that underlie some of their psychotomimetic effects. That is, perhaps some symptoms of depression can be understood as occupying the opposite end of a spectrum where elements of psychosis can be found on the other side. This review aims at reviewing the evidence underlying a proposed continuum hypothesis of psychotomimetic rapid antidepressants, suggesting that a range of psychotomimetic interventions are also acute antidepressants as well as trying to explain these common features in a hierarchical predictive coding framework, where we hypothesise that these interventions share a common mechanism by increasing the flexibility of prior expectations. Neurobiological mechanisms at play and the role of different neuromodulatory systems affected by these interventions and their role in controlling the precision of prior expectations and new sensory evidence will be reviewed. The proposed hypothesis will also be discussed in relation to other existing theories of antidepressants. We also suggest a number of novel experiments to test the hypothesis and highlight research areas that could provide further insights, in the hope to better understand the acute antidepressant properties of these interventions.

In search for the most optimal EEG method: A practical evaluation of a water-based electrode EEG system

The study assessed a mobile electroencephalography system with water-based electrodes for its applicability in cognitive and behavioural neuroscience. It was compared to a standard gel-based wired system. Electroencephalography was recorded on two occasions (first with gel-based, then water-based system) as participants completed the flanker task. Technical and practical considerations for the application of the water-based system are reported based on participant and experimenter experiences. Empirical comparisons focused on electroencephalography data noise levels, frequency power across four bands (theta, alpha, low beta and high beta) and event-related components (P300 and ERN). The water-based system registered more noise compared to the gel-based system which resulted in increased loss of data during artefact rejection. Signal-to-noise ratio was significantly lower for the water-based system in the parietal channels which affected the observed parietal beta power. It also led to a shift in topography of the maximal P300 activity from parietal to frontal regions. The water-based system may be prone to slow drift noise which may affect the reliability and consistency of low-frequency band analyses. Practical considerations for the use of water-based electrode electroencephalography systems are provided.

Resting-state connectivity studies as a marker of the acute and delayed effects of subanaesthetic ketamine administration in healthy and depressed individuals: A systematic review

Acute ketamine administration has been widely used in neuroimaging research to mimic psychosis-like symptoms. Within the last two decades, ketamine has also emerged as a potent, fast-acting antidepressant. The delayed effects of the drug, observed 2–48 h after a single infusion, are associated with marked improvements in depressive symptoms. At the systems’ level, several studies have investigated the acute ketamine effects on brain activity and connectivity; however, several questions remain unanswered around the brain changes that accompany the drug’s antidepressant effects and how these changes relate to the brain areas that appear with altered function and connectivity in depression. This review aims to address some of these questions by focusing on resting-state brain connectivity. We summarise the studies that have examined connectivity changes in treatment-naïve, depressed individuals and those studies that have looked at the acute and delayed effects of ketamine in healthy and depressed volunteers. We conclude that brain areas that are important for emotional regulation and reward processing appear with altered connectivity in depression whereas the default mode network presents with increased connectivity in depressed individuals compared to healthy controls. This finding, however, is not as prominent as the literature often assumes. Acute ketamine administration causes an increase in brain connectivity in healthy volunteers. The delayed effects of ketamine on brain connectivity vary in direction and appear to be consistent with the drug normalising the changes observed in depression. The limited number of studies however, as well as the different approaches for resting-state connectivity analysis make it very difficult to draw firm conclusions and highlight the importance of data sharing and larger future studies.

Validation of an emotional stop-signal task to probe individual differences in emotional response inhibition: Relationships with positive and negative urgency

Performance on an emotional stop-signal task designed to assess emotional response inhibition has been associated with Negative Urgency and psychopathology, particularly self-injurious behaviors. Indeed, difficulty inhibiting prepotent negative responses to aversive stimuli on the emotional stop-signal task (i.e. poor negative emotional response inhibition) partially explains the association between Negative Urgency and non-suicidal self-injury. Here, we combine existing data sets from clinical (hospitalised psychiatric inpatients) and non-clinical (community/student participants) samples aged 18–65 years ( N = 450) to examine the psychometric properties of this behavioural task and evaluate hypotheses that emotional stop-signal task metrics relate to distinct impulsive traits among participants who also completed the UPPS-P ( n = 223). We specifically predicted associations between worse negative emotional response inhibition (i.e. commission errors during stop-signal trials representing negative reactions to unpleasant images) and Negative Urgency, whereas commission errors to positive stimuli – reflecting worse positive emotional response inhibition – would relate to Positive Urgency. Results support the emotional stop-signal task’s convergent and discriminant validity: as hypothesised, poor negative emotional response inhibition was specifically associated with Negative Urgency and no other impulsive traits on the UPPS-P. However, we did not find the hypothesised association between positive emotional response inhibition and Positive Urgency. Correlations between emotional stop-signal task performance and self-report measures were the modest, similar to other behavioural tasks. Participants who completed the emotional stop-signal task twice ( n = 61) additionally provide preliminary evidence for test–retest reliability. Together, findings suggest adequate reliability and validity of the emotional stop-signal task to derive candidate behavioural markers of neurocognitive functioning associated with Negative Urgency and psychopathology.

Individual differences in theta-band oscillations in a spatial memory network revealed by electroencephalography predict rapid place learning

Spatial memory has been closely related to the medial temporal lobe and theta oscillations are thought to play a key role. However, it remains difficult to investigate medial temporal lobe activation related to spatial memory with non-invasive electrophysiological methods in humans. Here, we combined the virtual delayed-matching-to-place task, reverse-translated from the watermaze delayed-matching-to-place task in rats, with high-density electroencephalography recordings. Healthy young volunteers performed this computerised task in a virtual circular arena, which contained a hidden target whose location moved to a new place every four trials, allowing the assessment of rapid memory formation. Using behavioural measures as predictor variables for source reconstructed frequency-specific electroencephalography power, we found that inter-individual differences in ‘search preference’ during ‘probe trials’, a measure of one-trial place learning known from rodent studies to be particularly hippocampus-dependent, correlated predominantly with distinct theta-band oscillations (approximately 7 Hz), particularly in the right temporal lobe, the right striatum and inferior occipital cortex or cerebellum. This pattern was found during both encoding and retrieval/expression, but not in control analyses and could not be explained by motor confounds. Alpha-activity in sensorimotor and parietal cortex contralateral to the hand used for navigation also correlated (inversely) with search preference. This latter finding likely reflects movement-related factors associated with task performance, as well as a frequency difference in (ongoing) alpha-rhythm for high-performers versus low-performers that may contribute to these results indirectly. Relating inter-individual differences in ongoing brain activity to behaviour in a continuous rapid place-learning task that is suitable for a variety of populations, we could demonstrate that memory-related theta-band activity in temporal lobe can be measured with electroencephalography recordings. This approach holds great potential for further studies investigating the interactions within this network during encoding and retrieval, as well as neuromodulatory impacts and age-related changes.

Astrocytes in schizophrenia

Schizophrenia is a severe and clinically heterogenous mental disorder affecting approximately 1% of the population worldwide. Despite tremendous achievements in the field of schizophrenia research, its precise aetiology remains elusive. Besides dysfunctional neuronal signalling, the pathophysiology of schizophrenia appears to involve molecular and functional abnormalities in glial cells, including astrocytes. This article provides a concise overview of the current evidence supporting altered astrocyte activity in schizophrenia, which ranges from findings obtained from post-mortem immunohistochemical analyses, genetic association studies and transcriptomic investigations, as well as from experimental investigations of astrocyte functions in animal models. Integrating the existing data from these research areas strongly suggests that astrocytes have the capacity to critically affect key neurodevelopmental and homeostatic processes pertaining to schizophrenia pathogenesis, including glutamatergic signalling, synaptogenesis, synaptic pruning and myelination. The further elucidation of astrocytes functions in health and disease may, therefore, offer new insights into how these glial cells contribute to abnormal brain development and functioning underlying this debilitating mental disorder.

Lifting the lid on impact and peer review

Brain and Neuroscience Advances has grown in tandem with the British Neuroscience Association’s campaign to build Credibility in Neuroscience, which encourages actions and initiatives aimed at improving reproducibility, reliability and openness. This commitment to credibility impacts not only what the Journal publishes, but also how it operates. With that in mind, the Editorial Board sought the views of the neuroscience community on the peer review process, and on how they should respond to the Journal Impact Factor that will be assigned to Brain and Neuroscience Advances. In this editorial, we present the results of a survey of neuroscience researchers conducted in the autumn of 2020 and discuss the broader implications of our findings for the Journal and the neuroscience community.

Dissociating the effects of distraction and proactive interference on object memory through tests of novelty preference

Encoding information into memory is sensitive to distraction while retrieving that memory may be compromised by proactive interference from pre-existing memories. These two debilitating effects are common in neuropsychiatric conditions, but modelling them preclinically to date is slow as it requires prolonged operant training. A step change would be the validation of functionally equivalent but fast, simple, high-throughput tasks based on spontaneous behaviour. Here, we show that spontaneous object preference testing meets these requirements in the subchronic phencyclidine rat model for cognitive impairments associated with schizophrenia. Subchronic phencyclidine rats show clear memory sensitivity to distraction in the standard novel object recognition task. However, due to this, standard novel object recognition task cannot assess proactive interference. Therefore, we compared subchronic phencyclidine performance in standard novel object recognition task to that using the continuous novel object recognition task, which offers minimal distraction, allowing disease-relevant memory deficits to be assessed directly. We first determined that subchronic phencyclidine treatment did not affect whisker movements during object exploration. Subchronic phencyclidine rats exhibited the expected distraction standard novel object recognition task effect but had intact performance on the first continuous novel object recognition task trial, effectively dissociating distraction using two novel object recognition task variants. In remaining continuous novel object recognition task trials, the cumulative discrimination index for subchronic phencyclidine rats was above chance throughout, but, importantly, their detection of object novelty was increasingly impaired relative to controls. We attribute this effect to the accumulation of proactive interference. This is the first demonstration that increased sensitivity to distraction and proactive interference, both key cognitive impairments in schizophrenia, can be dissociated in the subchronic phencyclidine rat using two variants of the same fast, simple, spontaneous object memory paradigm.

Hot and cold executive functions in the brain: A prefrontal-cingular network

Executive functions, or cognitive control, are higher-order cognitive functions needed for adaptive goal-directed behaviours and are significantly impaired in majority of neuropsychiatric disorders. Different models and approaches are proposed for describing how executive functions are functionally organised in the brain. One popular and recently proposed organising principle of executive functions is the distinction between hot (i.e. reward or affective-related) versus cold (i.e. purely cognitive) domains of executive functions. The prefrontal cortex is traditionally linked to executive functions, but on the other hand, anterior and posterior cingulate cortices are hugely involved in executive functions as well. In this review, we first define executive functions, their domains, and the appropriate methods for studying them. Second, we discuss how hot and cold executive functions are linked to different areas of the prefrontal cortex. Next, we discuss the association of hot versus cold executive functions with the cingulate cortex, focusing on the anterior and posterior compartments. Finally, we propose a functional model for hot and cold executive function organisation in the brain with a specific focus on the fronto-cingular network. We also discuss clinical implications of hot versus cold cognition in major neuropsychiatric disorders (depression, schizophrenia, anxiety disorders, substance use disorder, attention-deficit hyperactivity disorder, and autism) and attempt to characterise their profile according to the functional dominance or manifest of hot–cold cognition. Our model proposes that the lateral prefrontal cortex along with the dorsal anterior cingulate cortex are more relevant for cold executive functions, while the medial–orbital prefrontal cortex along with the ventral anterior cingulate cortex, and the posterior cingulate cortex are more closely involved in hot executive functions. This functional distinction, however, is not absolute and depends on several factors including task features, context, and the extent to which the measured function relies on cognition and emotion or both.