Owen O’Daly

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

A systematic review of the relationship between eating, weight and inhibitory control using the stop signal task.

Altered inhibitory control (response inhibition, reward-based inhibition, cognitive inhibition, reversal learning) has been implicated in eating disorders (EDs) and obesity. It is unclear, however, how different types of inhibitory control contribute to eating and weight-control behaviours. This review evaluates the relationship between one aspect of inhibitory control (a reactive component of motor response inhibition measured by the stop signal task) and eating/weight in clinical and non-clinical populations. Sixty-two studies from 58 journal articles were included. Restrained eaters had diminished reactive inhibitory control compared to unrestrained eaters, and showed greatest benefit to their eating behaviour from manipulations of inhibitory control. Obese individuals may show less reactive inhibitory control but only in the context of food-specific inhibition or after executive resources are depleted. Of the limited studies in EDs, the majority found no impairment in reactive inhibitory control, although findings are inconsistent. Thus, altered reactive inhibitory control is related to some maladaptive eating behaviours, and hence may provide a therapeutic target for behavioural manipulations and/or neuromodulation. However, other types of inhibitory control may also contribute. Methodological and theoretical considerations are discussed.

Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit—a mechanism of relevance to resistant depression?

Background. Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods. Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results. Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion. Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

ABSTRACT Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Proactive and reactive inhibitory control in eating disorders

Altered inhibitory control has been implicated in the development and maintenance of eating disorders (ED), however it is unclear how different types of inhibitory control are affected across the EDs. We explored whether individuals with bulimia nervosa (BN), binge eating disorder (BED) and anorexia nervosa (AN) differed from healthy individuals (HC) on two types of motor inhibitory control: proactive inhibition (related to the preparation/initiation of a response) and reactive inhibition (withholding a response in reaction to a signal). Ninety-four women (28 AN, 27 BN, 11 BED, 28 HC) completed two neuropsychological tasks (a cued reaction time task and a stop signal task), and questionnaires assessing clinical variables, mood, anxiety, and inhibitory control. Self-reported inhibitory control was poorer in women with BN compared to the HC and AN groups, but greater in women with AN compared to all other groups. However, no group differences in reactive inhibition were observed. Proactive inhibition was augmented in women with AN compared to HC, and this was related to self-reported intolerance of uncertainty. The findings suggest that proactive inhibition may be a relevant target for behavioural interventions for AN, and call for further research into the relationship between intolerance of uncertainty and proactive inhibition.

Attentional Modulation of Source Attribution in First-Episode Psychosis: A Functional Magnetic Resonance Imaging Study

BACKGROUND In patients with schizophrenia, the misattribution of self-generated events to an external source is associated with the presence of psychotic symptoms. The aim of this study was to investigate how this misattribution is influenced by dysfunction of attentional processing, which is also impaired in schizophrenia. METHODS Participants underwent functional Magnetic Resonance Imaging (fMRI) while listening to prerecorded speech. Their expectancies were manipulated using visual cues that were either congruent (valid) or incongruent (invalid) with the speech. The source (self/other) and the acoustic quality (undistorted/distorted) of the speech were also manipulated. Twenty patients with first-episode psychosis (FEP) and 20 matched healthy controls (HC) were tested. RESULTS When listening to self-generated speech preceded by an invalid (other speech) cue, relative to HC, FEP patients showed a trend to misidentify their own speech as that of another person. Analysis of fMRI data showed that FEP patients had reduced activation in the right middle temporal gyrus (MTG) and left precuneus (Pc) relative to HC. Within the FEP group, the level of activation in the right MTG was negatively correlated with the severity of their positive psychotic symptoms. CONCLUSIONS Impaired attentional modulation in schizophrenia may contribute to the tendency for FEP patients to misattribute the source of self-generated material, and this may be mediated by the right MTG and Pc, regions that are involved in both self-referential processing and the integration of sensory information.

Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study

Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased activity in speech-sensitive regions of the left posterior superior temporal gyrus (STG). Here, we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate STG activity using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF). We also examined the effects of rtfMRI-NF training on functional connectivity between the STG and other speech and language regions. Twelve patients with SCZ and treatment-refractory AVH were recruited to participate in the study and were trained to down-regulate STG activity using rtfMRI-NF, over four MRI scanner visits during a 2-week training period. STG activity and functional connectivity were compared pre- and post-training. Patients successfully learnt to down-regulate activity in their left STG over the rtfMRI-NF training. Post- training, patients showed increased functional connectivity between the left STG, the left inferior prefrontal gyrus (IFG) and the inferior parietal gyrus. The post-training increase in functional connectivity between the left STG and IFG was associated with a reduction in AVH symptoms over the training period. The speech-sensitive region of the left STG is a suitable target region for rtfMRI-NF in patients with SCZ and treatment-refractory AVH. Successful down-regulation of left STG activity can increase functional connectivity between speech motor and perception regions. These findings suggest that patients with AVH have the ability to alter activity and connectivity in speech and language regions, and raise the possibility that rtfMRI-NF training could present a novel therapeutic intervention in SCZ.

Proactive inhibition: An element of inhibitory control in eating disorders

The aetiology of eating disorders (EDs) is unclear, but many hypotheses implicate alterations in behavioural control. Specifically and because of its relevance to symptomatology, there has been much interest in inhibitory control, i.e., the ability to inhibit inappropriate/unwanted behaviours. This has been studied in relation to reactive motor inhibition (withholding a response in reaction to a signal), reward-based inhibition (e.g., temporal discounting paradigms) and to reversal learning (e.g., set shifting tasks assessing cognitive flexibility and compulsivity). However, there has been less explicit exploration of proactive inhibitory control, i.e., a preparatory form of inhibitory control where responses are pre-emptively suppressed to improve performance either in terms of a dynamic strategy (e.g., post-error slowing) or as a more general suppression in the context of uncertainty (e.g., when the appropriateness of a response is less certain). This review considers proactive inhibition within the context of broader conceptual considerations of inhibitory control in EDs, discusses the existing behavioural and neural evidence, and concludes that this is a construct worthy of further exploration.

Stimulating thought: a functional MRI study of transcranial direct current stimulation in schizophrenia

&NA; Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro‐cognitive effects; however, there is limited understanding of its mechanism. This was a double‐blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n‐back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The ‘real’ and ‘sham’ groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post‐transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post‐stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task‐related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro‐cognitive effects in schizophrenia.

Exploring psychotic symptoms: a comparison of motor related neuronal activation during and after acute psychosis

BackgroundDelusions and hallucinations are classic positive symptoms of schizophrenia. A contemporary cognitive theory called the ‘forward output model’ suggests that the misattribution of self-generated actions may underlie some of these types of symptoms, such as delusions of control – the experience of self-generated action being controlled by an external agency. In order to examine the validity of this suggestion, we performed a longitudinal functional magnetic resonance imaging (fMRI) study examining neuronal activation associated with motor movement during acute psychosis.MethodsWe studied brain activation using fMRI during a motor task in 11 patients with schizophrenia and 9 healthy controls. The patient group was tested at two time points separated by 6–8 weeks.ResultsAt initial testing, the patient group had a mean Positive and Negative Syndrome Scale score of 56.3, and showed significantly increased activation within the left inferior parietal lobe (IPL) compared to controls. Patients reported significantly decreased positive symptoms at 6–8 week followup and IPL activation had returned to normal. Our results demonstrate that first-rank positive symptoms are associated with hyperactivation in the secondary somatosensory cortex (IPL).ConclusionsThese findings lend further credence to the theory that a dysfunction in the sensory feedback system located in the IPL, and which is thought to underlie our sense of agency, may contribute to the aetiology of delusions of control.