Plasma Kynurenine Level is Associated With Left DLPFC Activity and Can Predict Treatment Response in Major Depressive Disorder

To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features that are promising as biomarkers. This study aimed to determine the relationship between blood metabolites related to treatment response to escitalopram and regional brain activity at rest and to find the characteristics of depression that respond to treatment. Blood metabolite levels and resting brain activity were measured in patients with depression (N = 65) before and after 6 weeks treatment with escitalopram and healthy controls (N = 36). Thirty-two patients (49.2%) showed clinical response (>50% reduction in Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. Pretreatment plasma kynurenine level and fractional amplitude of low-frequency fluctuations (fALFF) of the left dorsolateral prefrontal cortex (DLPFC) were lower in Responders, and their elevations after treatment were correlated with improvement in symptoms. Moreover, fALFF of the left DLPFC was significantly correlated with plasma kynurenine level in pretreatment patients with depression and healthy controls. Decreased kynurenine level and resting-state regional brain activity of the left DLPFC may be involved in the pathophysiology of depression in response to escitalopram treatment.

Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism

Delayed phase 18F-FP-CIT PET (dCIT) can assess the striatal dopamine transporter binding to detect degenerative parkinsonism (DP). Early phase 18F-FP-CIT (eCIT) can assess the regional brain activity for differential diagnosis among parkinsonism similar with 18F-FDG PET. We evaluated the diagnostic performance of dual phase 18F-FP-CIT PET (dual CIT) and 18F-FDG PET compared with clinical diagnosis in 141 subjects [36 with idiopathic Parkinson’s disease (IPD), 77 with multiple system atrophy (MSA), 18 with progressive supranuclear palsy (PSP), and 10 with non-DP)]. Visual assessment of eCIT, dCIT, dual CIT, 18F-FDG and 18F-FDG PET with dCIT was in agreement with the clinical diagnosis in 61.7%, 69.5%, 95.7%, 81.6%, and 97.2% of cases, respectively. ECIT showed about 90% concordance with non-DP and MSA, and 8.3% and 27.8% with IPD and PSP, respectively. DCIT showed ≥ 88% concordance with non-DP, IPD, and PSP, and 49.4% concordance with MSA. Dual CIT showed ≥ 90% concordance in all groups. 18F-FDG PET showed ≥ 90% concordance with non-DP, MSA, and PSP, but only 33.3% concordance with IPD. The combination of 18F-FDG and dCIT yielded ≥ 90% concordance in all groups. Dual CIT may represent a powerful alternative to the combination of 18F-FDG PET and dCIT for differential diagnosis of parkinsonian disorders.

Gray Matter and Regional Brain Activity Abnormalities in Subclinical Hypothyroidism

BackgroundSubclinical hypothyroidism (SCH) brain structure and resting state of functional activity have remained unexplored.PurposeTo investigate gray matter volume (GMV) and regional brain activity with the fractional amplitude of low-frequency fluctuations (fALFF) in subclinical hypothyroidism (SCH) patients before and after treatment.Material and MethodsWe enrolled 54 SCH and 41 age-, sex-, and education-matched controls. GMV and fALFF of SCH were compared with controls and between pre- and post-treatment within SCH group. Correlations of GMV and fALFF in SCH with thyroid function status and mood scales were assessed by multiple linear regression analysis.ResultsCompared to controls, GMV in SCH was significantly decreased in Orbital part of inferior frontal, superior frontal, pre-/postcentral, inferior occipital, and temporal pole gyrus. FALFF values in SCH were significantly increased in right angular, left middle frontal, and left superior frontal gyrus. After treatment, there were no significant changes in GMV and the local brain function compared to pre-treatment, however the GMV and fALFF of the defective brain areas were improved. Additionally, decreased values of fALFF in left middle frontal gyrus were correlated with increased mood scales.ConclusionIn this study we found that patients with SCH, the gray matter volume in some brain areas were significantly reduced, and regional brain activity was significantly increased. After treatment, the corresponding structural and functional deficiencies had a tendency for improvement. These changes may reveal the neurological mechanisms of mood disorder in SCH patients.

Mind the food: behavioural characteristics and imaging signatures of the specific handling of food objects

In our world with nearly omnipresent availability of attractive and palatable high-calorie food, the struggle against overweight and obesity is a major individual and public health challenge. Preference for unhealthy food and eating-related habits have a strong influence on health, suggesting that high-calorie food triggers fast and near-automatic reaching and grasping movements. Therefore, it is important to better understand the specific neural mechanisms that control the handling of food involving a coordinated interplay between sensoric, motoric, and cognitive subsystems. To this end, 30 healthy participants (Ø BMI: 22.86 kg/m2; BMI range: 19–30 kg/m2; 23 females) were instructed to collect one of two concurrently presented objects (food vs. office tools) by manual movement in virtual reality (VR) and on a touchscreen. Parallel to the task in VR, regional brain activity was measured by functional near-infrared spectroscopy (fNIRS). In the VR and on the touchscreen, stimulus recognition and selection were faster for food than for office tools. Yet, food was collected more slowly than office tools when measured in VR. On the background of increased brain activity in the right dorsolateral prefrontal cortex (dlPFC) during food trials, this suggests more behavioural control activity during handling foods. In sum, this study emphasizes the role of the right dlPFC in faster recognition and selection of food as part of a food-valuation network, more controlled handling of food in the VR which highlights the relevance of medium for modelling food-specific embodied cognitions.

Paradoxical fMRI overconnectivity upon chemogenetic silencing of the prefrontal cortex

While shaped and constrained by axonal connections, fMRI-based functional connectivity can reorganize in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity to whole-brain fMRI network organization remains unclear. Here we combine neural silencing, resting-state fMRI and in vivo electrophysiology to causally probe how inactivation of a cortical node affects brain-wide fMRI coupling in the mouse. We find that chronic suppression of the medial prefrontal cortex (PFC) via overexpression of a potassium channel paradoxically increases fMRI connectivity between the silenced area and its direct thalamo-cortical terminals. Acute chemogenetic inactivation of the PFC reproduces analogous patterns of fMRI overconnectivity, with increased fMRI coupling between polymodal thalamic regions and widespread cortical areas. Using multielectrode electrophysiological recordings, we further show that chemogenetic inactivation of the PFC results in enhanced slow (0.1 - 4 Hz) oscillatory coupling between fMRI overconnected areas, and that changes in δ band coherence are linearly correlated with corresponding increases in fMRI connectivity. These results provide causal evidence that cortical inactivation does not necessarily lead to reduced inter-areal coupling, but can counterintuitively increase fMRI connectivity via enhanced, less-localized slow oscillatory processes, with important implications for modelling and understanding fMRI overconnectivity in pathological states.

Altered Percent Amplitude of Fluctuation in Healthy Subjects After 36 h Sleep Deprivation

Objective: To investigate regional brain activity alteration in healthy subjects in a sleep deprivation (SD) status relative to a rested wakefulness status using a percent amplitude of fluctuation (PerAF) method.Methods: A total of 20 healthy participants (12 males, 8 females; age, 22.25 ± 1.12 years) were recruited. All participants underwent attention tests and resting-state functional MRI scans during rested wakefulness before SD and after 36 h SD, respectively. The PerAF method was applied to identify SD-related regional brain activity alteration. A ROC curve was conducted to evaluate the ability of the PerAF method in distinguishing different sleep statuses. The relationships between SD-induced brain alterations and attention deficits were determined by Pearson correlation analysis.Results: SD resulted in a 2.23% decrease in accuracy rate and an 8.82% increase in reaction time. SD was associated with increased PerAF differences in the bilateral visual cortex and bilateral sensorimotor cortex, and was associated with decreased PerAF differences in bilateral dorsolateral prefrontal cortex and bilateral cerebellum posterior lobe. These SD-induced brain alterations exhibited a high discriminatory power of extremely high AUC values (0.993–1) in distinguishing the two statuses. The accuracy rate positively correlated with the bilateral cerebellum posterior lobe, and bilateral dorsolateral prefrontal cortex, and negatively correlated with the bilateral sensorimotor cortex.Conclusions: Acute SD could lead to an ~8% attention deficit, which was associated with regional brain activity deficits. The PerAF method might work as a potential sensitivity biomarker for identifying different sleep statuses.

Evaluation of spontaneous regional brain activity in weight-recovered anorexia nervosa

Whereas research using structural magnetic resonance imaging (sMRI) reports sizable grey matter reductions in patients suffering from acute anorexia nervosa (AN) to be largely reversible already after short-term weight gain, many task-based and resting-state functional connectivity (RSFC) studies suggest persistent brain alterations even after long-term weight rehabilitation. First investigations into spontaneous regional brain activity using voxel-wise resting-state measures found widespread abnormalities in acute AN, but no studies have compared intrinsic brain activity properties in weight-recovered individuals with a history of AN (recAN) with healthy controls (HCs). SMRI and RSFC data were analysed from a sample of 130 female volunteers: 65 recAN and 65 pairwise age-matched HC. Cortical grey matter thickness was assessed using FreeSurfer software. Fractional amplitude of low-frequency fluctuations (fALFFs), mean-square successive difference (MSSD), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VHMC), and degree centrality (DC) were calculated. SMRI and RSFC data were analysed from a sample of 130 female volunteers: 65 recAN and 65 pairwise age-matched HCs. Cortical grey matter thickness was assessed using FreeSurfer software. Fractional amplitude of low-frequency fluctuations (fALFF), mean-square successive difference (MSSD), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VHMC), and degree centrality (DC) were calculated. Abnormal regional homogeneity found in acute AN seems to normalize in recAN, supporting assumptions of a state rather than a trait marker. Aberrant fALFF values in the cerebellum and the infertior temporal gyrus could possibly hint towards trait factors or a scar (the latter, e.g., from prolonged periods of undernutrition), warranting further longitudinal research.