Differences in regional grey matter volumes in currently ill patients with anorexia nervosa.

Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel-based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty-six individuals with AN and 27 healthy controls underwent a T1-weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE-Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology.

Saccades under Mental Load in Infantile Nystagmus Syndrome and Controls.

SIGNIFICANCE: This study compares saccades and visual task performance in patients with infantile nystagmus syndrome (INS) with that in normally sighted individuals under mental load. The results highlighted that to more completely evaluate INS therapies recognition time should also be measured with mental load, resembling real-world conditions. PURPOSE: Patients with INS may complain of "being slow to see." Stress is reported to worsen nystagmus and to prolong visual recognition time. We hypothesized that the effects of mental load on timing indices of visual recognition, for example, saccade latency, target acquisition time, target viewing time, and subjects' reaction time, differ between the INS and control groups. METHODS: Eye movements were recorded when participants (INS group, n = 15; controls, n = 25) reported the direction of tumbling-E targets presented randomly across ±25°. The task was repeated with both mental arithmetic and time restriction to impose high mental load, confirmed through subjective ratings and heart rate measurement. RESULTS: Mental load increased saccade latency (mean, 32.69 milliseconds; 95% confidence interval [CI], 21.17 to 44.20 milliseconds; P < .001) and target acquisition time (57.00 milliseconds; 95% CI, 34 to 81 milliseconds; P < .001). Patients with INS showed longer saccade latency (39.79 milliseconds; 95% CI, 23.98 to 55.62 milliseconds; P < .001) and target acquisition time (134.00 milliseconds; 95% CI, 96 to 172 milliseconds; P < .001) compared with controls. The interaction between task and group was significant for saccade gain (0.11; 95% CI, 0.02 to 0.19; P = .015), target acquisition time (37.93 milliseconds; 95% CI, 36.91 to 38.96 milliseconds; P = .011), and subjects' reaction time (95.37 milliseconds; 95% CI, 65.91 to 124.84 milliseconds; P = .043). There was an inverse correlation between the changes in subjects' response errors and target viewing time with mental load only for controls (r = -0.484, P = .014). Total foveation exposure time and target viewing time remained unchanged. CONCLUSIONS: Mental load worsens "being slow to see" in INS because of delayed target acquisition and possibly because efficiency of visual processing decreases more in patients with INS compared with controls. To investigate outcomes of INS therapies, visual recognition time should be also measured with mental load.

Task-induced Changes in Idiopathic Infantile Nystagmus Vary with Gaze.

PURPOSE: Investigations of infantile nystagmus syndrome (INS) at center or at the null position have reported that INS worsens when visual demand is combined with internal states, e.g. stress. Visual function and INS parameters such as foveation time, frequency, amplitude, and intensity can also be influenced by gaze position. We hypothesized that increases from baseline in visual demand and mental load would affect INS parameters at the null position differently than at other gaze positions. METHODS: Eleven participants with idiopathic INS were asked to determine the direction of Tumbling-E targets, whose visual demand was varied through changes in size and contrast, using a staircase procedure. Targets appeared between ±25° in 5° steps. The task was repeated with both mental arithmetic and time restriction to impose higher mental load, confirmed through subjective ratings and concurrent physiological measurements. RESULTS: Within-subject comparisons were limited to the null and 15° away from it. No significant main effects of task on any INS parameters were found. At both locations, high mental load worsened task performance metrics, i.e. lowest contrast (P = .001) and smallest optotype size reached (P = .012). There was a significant interaction between mental load and gaze position for foveation time (P = .02) and for the smallest optotype reached (P = .028). The increase in threshold optotype size from the low to high mental load was greater at the null than away from it. During high visual demand, foveation time significantly decreased from baseline at the null as compared to away from it (mean difference ± SE: 14.19 ± 0.7 msec; P = .010). CONCLUSIONS: Under high visual demand, the effects of increased mental load on foveation time and visual task performance differed at the null as compared to 15° away from it. Assessment of these effects could be valuable when evaluating INS clinically and when considering its impact on patients' daily activities.

Body Image in Anorexia Nervosa: Body Size Estimation Utilising a Biological Motion Task and Eyetracking.

OBJECTIVE: Anorexia nervosa (AN) is a psychiatric condition characterised by a distortion of body image. However, whether individuals with AN can accurately perceive the size of other individuals' bodies is unclear. METHOD: In the current study, 24 women with AN and 24 healthy control participants undertook two biological motion tasks while eyetracking was performed: to identify the gender and to indicate the walkers' body size. RESULTS: Anorexia nervosa participants tended to 'hyperscan' stimuli but did not demonstrate differences in how visual attention was directed to different body areas, relative to controls. Groups also did not differ in their estimation of body size. DISCUSSION: The hyperscanning behaviours suggest increased anxiety to disorder-relevant stimuli in AN. The lack of group difference in the estimation of body size suggests that the AN group was able to judge the body size of others accurately. The findings are discussed in terms of body image distortion specific to oneself in AN.

Visual search in infantile nystagmus syndrome.

CLINICAL RELEVANCE: Research on infantile nystagmus syndrome (INS) and visual search is limited. Conducting this research could assist practitioners in understanding how INS affects the real-life visual activities of patients and aid in developing new clinical visual function assessments for INS. BACKGROUND: The aim of this work is to investigate how subjects with INS perform visual search tasks, and, particularly, to assess how INS subjects perform when targets are located at their null position or away from it, and when under additional cognitive demands. METHODS: INS subjects (N = 15) and controls (N = 20) performed conjunction and feature search tasks, both with and without mental arithmetic. Search performance was assessed using log-transformed total search time, gaze-dependent search time, and accuracy. Cognitive demand was quantified by pupil size and the NASA task-load index score. RESULTS: INS subjects showed longer search times compared to controls in conjunction search (P < 0.01), but not in feature search. Within INS and control subjects, the total search times were significantly increased by the addition of mental arithmetic (P < 0.0001). There was no difference in gaze-dependent search times between null target position and 15° away from null target position of subjects in conjunction search (P > 0.05). Accuracies were 100% for both control and INS subjects in both conjunction and feature search. CONCLUSION: Conjunction visual search was impaired in adult INS subjects, and further worsened under increased cognitive demand. The null position did not affect the visual search performance in INS.

Perception of Coherent Motion in Infantile Nystagmus Syndrome.

Purpose: Research on infantile nystagmus syndrome (INS) and motion perception is limited. We investigated how individuals with INS perform coherent motion tasks. Particularly, we assessed how the null position affects their performance. Methods: Subjects with INS and controls identified the direction of coherent motion stimuli (22 subjects with INS and 13 controls) in a two-alternative forced-choice design. For subjects with INS, testing was done at the null position and 15 degrees away from it. If there was no null, testing was done at primary gaze position and 15 degrees away from primary. For controls, testing was done at primary gaze position and 20 degrees away from primary. Horizontal and vertical motion coherence thresholds were determined. Results: Subjects with INS showed significantly higher horizontal and vertical motion coherence thresholds compared with controls at both gaze positions (P < 0.001). Within the INS group, for 12 subjects with INS who had an identified null position, no differences in coherence thresholds were found between their null and 15 degrees away from it (P > 0.05). Conclusions: Coherent motion perception was impaired in subjects with INS. The null position did not significantly influence motion coherence thresholds for either horizontal or vertical motion.

Velocity Discrimination in Infantile Nystagmus Syndrome.

Purpose: Research on infantile nystagmus syndrome (INS) and velocity discrimination is limited, and no research has examined velocity discrimination in subjects with INS at their null position and away from it. This study aims to investigate how individuals with INS perform, compared with controls, when carrying out velocity discrimination tasks. Particularly, the study aims to assess how the null position affects their performance. Methods: INS subjects (N = 21, mean age 24 years; age range, 15-34 years) and controls (N = 16, mean age 26 years; age range, 22-39 years) performed horizontal and vertical velocity discrimination tasks at two gaze positions. Eighteen INS subjects were classified as idiopathic INS and three had associated visual disorders (two had oculocutaneous albinism, and one had congenital cataract). For INS subjects, testing was done at the null position and 15° away from it. If there was no null, testing was done at primary gaze position and 15° away from primary. For controls, testing was done at primary gaze position and 20° away from primary. Horizontal and vertical velocity discrimination thresholds were determined and analyzed. Results: INS subjects showed significantly higher horizontal and vertical velocity discrimination thresholds compared with controls at both gaze positions (P < 0.001). Horizontal thresholds for INS subjects were elevated more than vertical thresholds (P < 0.0001) for INS subjects but not for controls. Within the INS group, 12 INS subjects who had an identified null position showed significantly lower horizontal and vertical thresholds at the null than at 15° away from it (P < 0.05). Conclusions: Velocity discrimination was impaired in INS subjects, with better performance at the null. These findings could assist in understanding how INS affects the daily activities of patients in tasks involving moving objects, and aid in developing new clinical visual function assessments for INS.

Fostering Spontaneous Visual Attention in Children on the Autism Spectrum: A Proof-of-Concept Study Comparing Singing and Speech.

Children on the autism spectrum are reported to have lower rates of social gaze as early as toddlerhood, and this pattern persists across the lifespan. Finding ways to promote more natural and spontaneous engagement in social interactions may help to boost developmental opportunities in the child's home and community settings. This proof-of-concept study hypothesized that a video of a singer would elicit more attention to the performer, particularly to her face, than a video of her reading a story, and that the child's familiarity with the material would enhance attention. Sixteen children on the autism spectrum (7-10 years old) watched 4 videos 1 min long comprising a favorite song or story, and an unfamiliar song and story. Eye movements were recorded, and three-way repeated measures ANOVAs examined the proportion of total valid visual dwell time and fixations, in each trial and each target area. For proportion of both dwell time and fixation counts, children were significantly more likely to look at the performer's face and body and less at the prop during singing than story-telling and when familiar rather than unfamiliar material was presented. These findings raise important issues for supporting children to naturally initiate looking toward a person's face. Autism Res 2018, 11: 732-737. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children on the autism spectrum may have difficulty looking at people, particularly their faces. In this study, children watched videos of someone singing or reading a story. The results show that children look more at the person if they were singing and if the story was familiar to them. Using songs and familiar stories may be a way to help children with autism to naturally engage with others.

An Overlooked Brain Region in the Aetiology of Anorexia Nervosa: The Importance of Behaviourally Driven Neuroimaging Analysis.

The neurobiological contributions to anorexia nervosa (AN) remain poorly understood, hindering the development of effective neurobiological treatments such as medications and brain stimulation. A large number of studies have been undertaken utilising neuroimaging techniques, such as magnetic resonance imaging (MRI), to gain a better understanding of the brain mechanisms involved in the illness. However, the analyses undertaken by many studies have utilised a whole-brain analytical approach as much of this research has been exploratory in nature. This is, however, problematic as small brain regions that differ between groups may not have the statistical power to produce statistically significant results. This is highlighted in a recent study undertaken by our group utilising diffusion-weighted imaging. In this research, we identified widespread white matter microstructural differences in individuals with AN, but only showed differences in a small brain region (the superior colliculus) when a region-of-interest approach that was driven by behavioural findings was utilised. The importance of hypothesis-driven neuroimaging analyses is discussed in this article.

Self-reported and behavioural impulsivity in anorexia nervosa.

AIM: To examine how self-reported and behavioural impulsivity are related in anorexia nervosa (AN). METHODS: Twenty-four females with AN and 25 healthy controls (HC) participant in the study. Self-reported impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). The scale yields three second-order factors: Attentional, motor and non-planning. Behavioural impulsivity was investigated with the continuous performance test (CPT), a computer-based task of sustained attention in which numbers are flashed briefly on screen and participants are required to click the mouse when the same number appears consecutively. The rate of commission and omission errors can be used a measure of behavioural imulsivity. RESULTS: AN participants self-reported increased attentional [AN: 20.67 (3.64), HC: 13.88 (2.91), P = 0.001] and reduced motor impulsivity [AN: 11.55 (2.28), HC: 14.08 (2.78), P = 0.002]. The rate of omission or commission errors on the CPT did not differ between groups (P > 0.05). BIS-11 and CPT measures did not significantly correlate, but attentional impulsivity was related to negative mood states in AN (depression: r = 0.52, P = 0.010, anxiety: r = 0.55, P = 0.006, stress: r = 0.57, P = 0.004). CONCLUSION: The discrepancy between self-reported and behavioural impulsivity are discussed in terms of perfectionism in AN. Furthermore, it is suggested that improving negative mood states may resolve this inconsistency in AN.

Saccadic Eye Movements in Anorexia Nervosa.

BACKGROUND: Anorexia Nervosa (AN) has a mortality rate among the highest of any mental illness, though the factors involved in the condition remain unclear. Recently, the potential neurobiological underpinnings of the condition have become of increasing interest. Saccadic eye movement tasks have proven useful in our understanding of the neurobiology of some other psychiatric illnesses as they utilise known brain regions, but to date have not been examined in AN. The aim of this study was to investigate whether individuals with AN differ from healthy individuals in performance on a range of saccadic eye movements tasks. METHODS: 24 females with AN and 25 healthy individuals matched for age, gender and premorbid intelligence participated in the study. Participants were required to undergo memory-guided and self-paced saccade tasks, and an interleaved prosaccade/antisaccade/no-go saccade task while undergoing functional magnetic resonance imaging (fMRI). RESULTS: AN participants were found to make prosaccades of significantly shorter latency than healthy controls. AN participants also made an increased number of inhibitory errors on the memory-guided saccade task. Groups did not significantly differ in antisaccade, no-go saccade or self-paced saccade performance, or fMRI findings. DISCUSSION: The results suggest a potential role of GABA in the superior colliculus in the psychopathology of AN.

Resting state functional connectivity in anorexia nervosa.

Anorexia Nervosa (AN) is a serious psychiatric illness characterised by a disturbance in body image, a fear of weight gain and significantly low body weight. The factors involved in the genesis and maintenance of AN are unclear, though the potential neurobiological underpinnings of the condition are of increasing interest. Through the investigation of functional connectivity of the brain at rest, information relating to neuronal communication and integration of information that may relate to behaviours and cognitive symptoms can be explored. The aim of this study was to investigate functional connectivity of the default mode network, and sensorimotor and visual networks in AN. 26 females with AN and 27 healthy control participants matched for age, gender and premorbid intelligence underwent a resting state functional magnetic resonance imaging scan. Default mode network functional connectivity did not differ between groups. AN participants displayed reduced functional connectivity between the sensorimotor and visual networks, in comparison to healthy controls. This finding is discussed in terms of differences in visuospatial processing in AN and the distortion of body image experienced by these individuals. Overall, the findings suggest that sensorimotor and visual network connectivity may be related to visuospatial processing in AN, though, further research is required.

Comprehensive neurocognitive assessment of patients with anorexia nervosa.

AIM: To utilise a comprehensive cognitive battery to gain a better understanding of cognitive performance in anorexia nervosa (AN). METHODS: Twenty-six individuals with AN and 27 healthy control participants matched for age, gender and premorbid intelligence, participated in the study. A standard cognitive battery, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery, was used to investigate performance on seven cognitive domains with the use of 10 different tasks: speed of processing [Brief Assessment Of Cognition In Schizophrenia: Symbol Coding, Category Fluency: Animal Naming (Fluency) and Trail Making Test: Part A], attention/vigilance [Continuous Performance Test - Identical Pairs (CPT-IP)], working memory [Wechsler Memory Scale (WMS(®)-III): Spatial Span, and Letter-Number Span (LNS)], verbal learning [Hopkins Verbal Learning Test - Revised], visual learning [Brief Visuospatial Memory Test - Revised], reasoning and problem solving [Neuropsychological Assessment Battery: Mazes], and social cognition [Mayer-Salovey-Caruso Emotional Intelligence Test: Managing Emotions]. Statistical analyses involved the use of multivariate and univariate analyses of variance. RESULTS: Analyses conducted on the cognitive domain scores revealed no overall significant difference between groups nor any interaction between group and domain score [F(1,45) = 0.73, P = 0.649]. Analyses conducted on each of the specific tasks within the cognitive domains revealed significantly slower reaction times for false alarm responses on the CPT-IP task in AN [F(1,51) = 12.80, P < 0.01, Cohen's d = 0.982] and a trend towards poorer performance in AN on the backward component of the WMS(®)-III Spatial Span task [F(1,51) = 5.88, P = 0.02, Cohen's d = -0.665]. The finding of slower reaction times of false alarm responses is, however, limited due to the small number of false alarm responses for either group. CONCLUSION: The findings are discussed in terms of poorer capacity to manipulate and process visuospatial material in AN.

Square wave jerks and anxiety as distinctive biomarkers for anorexia nervosa.

PURPOSE: The factors contributing to the cause and maintenance of anorexia nervosa (AN) are poorly understood, though increasing interest surrounds the neurobiological underpinnings of the condition. The examination of saccadic eye movements has proven useful in our understanding of the neurobiology of some other psychiatric illnesses, as they utilize identifiable brain circuits. Square wave jerks (SWJs), which describe an involuntary saccade away and back to fixation, have been observed to occur at abnormally high rates in neurodegenerative disorders and some psychiatric illnesses, but have not been examined in AN. Therefore, the aim of this study was to investigate whether individuals with AN and healthy control (HC) individuals differ in SWJ rate during attempted fixation. METHODS: Square wave jerk frequency was compared across 23 female participants with AN and 22 HC participants matched for age, sex, and premorbid intelligence. RESULTS: Anorexia nervosa participants were found to make SWJs at a significantly higher rate than HC participants. The rate of SWJs in AN was also found to negatively correlate with anxiety. Square wave jerk rate and anxiety were found to correctly classify groups, with an accuracy of 87% for AN participants and 95.5% for HCs. CONCLUSIONS: Given our current understanding of saccadic eye movements, the findings suggest a potential role of γ-aminobutyric acid (GABA) in the superior colliculus, frontal eye fields, or posterior parietal cortex in the psychopathology of AN.