Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients. METHOD: We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated. RESULTS: Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups. DISCUSSION: The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.

Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms.

BACKGROUND: Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED. AIM: This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration. METHODS: Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test. RESULTS AND CONCLUSIONS: The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.

An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

Heritability of cervical spinal cord structure.

OBJECTIVE: Measures of spinal cord structure can be a useful phenotype to track disease severity and development; this observational study measures the hereditability of cervical spinal cord anatomy and its correlates in healthy human beings. METHODS: Twin data from the Human Connectome Project were analyzed with semiautomated spinal cord segmentation, evaluating test-retest reliability and broad-sense heritability with an AE model. Relationships between spinal cord metrics, general physical measures, regional brain structural measures, and motor function were assessed. RESULTS: We found that the spinal cord C2 cross-sectional area (CSA), left-right width (LRW), and anterior-posterior width (APW) are highly heritable (85%-91%). All measures were highly correlated with the brain volume, and CSA only was positively correlated with thalamic volumes (p = 0.005) but negatively correlated with the occipital cortex area (p = 0.001). LRW was correlated with the participant's height (p = 0.00027). The subjects' sex significantly influenced these metrics. Analyses of a test-retest data set confirmed validity of the approach. CONCLUSIONS: This study provides the evidence of genetic influence on spinal cord structure. MRI metrics of cervical spinal cord anatomy are robust and not easily influenced by nonpathological environmental factors, providing a useful metric for monitoring normal development and progression of neurodegenerative disorders affecting the spinal cord, including-but not limited to-spinal cord injury and MS.

Cerebellar Contribution to Motor and Non-motor Functions in Parkinson's Disease: A Meta-Analysis of fMRI Findings.

Background: Parkinson's disease (PD) results in both motor and non-motor symptoms. Traditionally, the underlying mechanism of PD has been linked to neurodegeneration of the basal ganglia. Yet it does not adequately account for the non-motor symptoms of the disease, suggesting that other brain regions may be involved. One such region is the cerebellum, which is known to be involved, together with the basal ganglia, in both motor and non-motor functions. Many studies have found the cerebellum to be hyperactive in PD patients, a finding that is seldom discussed in detail, and warrants further examination. The current study thus aims to examine quantitively the current literature on the cerebellar involvement in both motor and non-motor functioning in PD. Methods: A meta-analysis of functional neuroimaging literature was conducted with Seed-based D mapping. Only the studies testing functional activation in response to motor and non-motor paradigms in PD and healthy controls (HC) were included in the meta-analysis. Separate analyses were conducted by including only studies with non-motor paradigms, as well as meta-regressions with UPDRS III scores and disease duration. Results: A total of 57 studies with both motor and non-motor paradigms fulfilled our inclusion criteria and were included in the meta-analysis, which revealed hyperactivity in Crus I-II and vermal III in PD patients compared to HC. An analysis including only studies with cognitive paradigms revealed a cluster of increased activity in PD patients encompassing lobule VIIB and VIII. Another meta-analysis including the only 20 studies that employed motor paradigms did not reveal any significant group differences. However, a descriptive analysis of these studies revealed that 60% of them reported cerebellar hyperactivations in PD and included motor paradigm with significant cognitive task demands, as opposed to 40% presenting the opposite pattern and using mainly force grip tasks. The meta-regression with UPDRS III scores found a negative association between motor scores and activation in lobule VI and vermal VII-VIII. No correlation was found with disease duration. Discussion: The present findings suggest that one of the main cerebellar implications in PD is linked to cognitive functioning. The negative association between UPDRS scores and activation in regions implicated in motor functioning indicate that there is less involvement of these areas as the disease severity increases. In contrast, the lack of correlation with disease duration seems to indicate that the cerebellar activity may be a compensatory mechanism to the dysfunctional basal ganglia, where certain sub-regions of the cerebellum are employed to cope with motor demands. Yet future longitudinal studies are needed to fully address this possibility.

Brain changes after spinal cord injury, a quantitative meta-analysis and review.

Spinal Cord Injuries (SCI) lead to alterations in brain structure and brain function by direct effects of nerve damage, by secondary mechanisms, and also by longer term injury consequences such as paralysis and neuropathic pain. Here, we review neuroimaging studies of patients with traumatic spinal cord injuries, perform a quantitative meta-analysis of motor and motor imagery studies, summarize structural studies, evidence of cortical reorganization, and provide an overview of diffusion and spectroscopy studies. The meta-analysis showed significantly altered motor cortex, as well as cerebellar and parietal lobe changes, and qualitatively consistent reports of alterations in somatosensory brain structure, cortical reorganization, white matter diffusion and thalamic metabolites. Larger samples in combination with standardized imaging protocols and data sharing will further our understanding of brain changes after SCI and help in defining short and long-term changes in brain systems in SCI patients. Such data would provide a basis for clinical trials, treatment outcomes, and guide novel interventions.

Responsivity of Periaqueductal Gray Connectivity Is Related to Headache Frequency in Episodic Migraine.

Migraineurs show hypersensitivity to sensory stimuli at various stages throughout the migraine cycle. A number of putative processes have been implicated including a dysfunction in the descending pain modulatory system in which the periaqueductal gray (PAG) is considered to play a crucial role. Recurring migraine attacks could progressively perturb this system, lowering the threshold for future attacks, and contribute to disease chronification. Here, we investigated PAG connectivity with other brain regions during a noxious thermal stimulus to determine changes in migraineurs, and associations with migraine frequency. 21 episodic migraine patients and 22 matched controls were included in the study. During functional MRI, a thermode was placed on the subjects' temple delivering noxious and non-noxious heat stimuli. A psychophysiological interaction (PPI) analysis was carried out to examine pain-induced connectivity of the PAG with other brain regions. The PPI analysis showed increased PAG connectivity with the S1 face representation area and the supplementary motor area, an area involved with pain expectancy, in patients with higher frequency of migraine attacks. PAG connectivity with regions involved with the descending pain modulatory system (i.e., prefrontal cortex) was decreased in the migraineurs versus healthy individuals. Our results suggest that high frequency migraineurs may have diminished resistance to cephalic pain and a less efficient inhibitory pain modulatory response to external stressor (i.e., noxious heat). The findings support the notion that in migraine there is less effective pain modulation (viz., decreased pain inhibition or increased pain facilitation), potentially contributing to increased occurrence of attacks/chronification of migraine.

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.

Obsessive-compulsivity and working memory are associated with differential prefrontal cortex and insula activation in adolescents with a recent diagnosis of an eating disorder.

The role of rumination at the beginning of eating disorder (ED) is not well understood. We hypothesised that impulsivity, rumination and restriction could be associated with neural activity in response to food stimuli in young individuals with eating disorders (ED). We measured neural responses with functional magnetic resonance imaging (fMRI), tested working memory (WM) and administered the eating disorders examination questionnaire (EDE-Q), Barratt impulsivity scale (BIS-11) and obsessive-compulsive inventory (OCI-R) in 15 adolescent females with eating disorder not otherwise specified (EDNOS) (mean age 15 years) and 20 age-matched healthy control females. We found that EDNOS subjects had significantly higher scores on the BIS 11, EDE-Q and OCI-R scales. Significantly increased neural responses to food images in the EDNOS group were observed in the prefrontal circuitry. OCI-R scores in the EDNOS group also significantly correlated with activity in the prefrontal circuitry and the cerebellum. Significantly slower WM responses negatively correlated with bilateral superior frontal gyrus activity in the EDNOS group. We conclude that ruminations, linked to WM, are present in adolescent females newly diagnosed with EDNOS. These may be risk factors for the development of an eating disorder and may be detectable before disease onset.