Striato-cortical functional connectivity changes in mild cognitive impairment with Lewy bodies.

BACKGROUND: Functional connectivity changes in clinically overt neurodegenerative diseases such as dementia with Lewy bodies have been described, but studies on connectivity changes in the pre-dementia phase are scarce. OBJECTIVES: We concentrated on evaluating striato-cortical functional connectivity differences between patients with Mild Cognitive Impairment with Lewy bodies and healthy controls and on assessing the relation to cognition. METHODS: Altogether, we enrolled 77 participants (47 patients, of which 35 met all the inclusion criteria for the final analysis, and 30 age- and gender-matched healthy controls, of which 28 met all the inclusion criteria for the final analysis) to study the seed-based connectivity of the dorsal, middle, and ventral striatum. We assessed correlations between functional connectivity in the regions of between-group differences and neuropsychological scores of interest (visuospatial and executive domains z-scores). RESULTS: Subjects with Mild Cognitive Impairment with Lewy Bodies, as compared to healthy controls, showed increased connectivity from the dorsal part of the striatum particularly to the bilateral anterior part of the temporal cortex with an association with executive functions. CONCLUSIONS: We were able to capture early abnormal connectivity within cholinergic and noradrenergic pathways that correlated with cognitive functions known to be linked to cholinergic/noradrenergic deficits. The knowledge of specific alterations may improve our understanding of early neural changes in pre-dementia stages and enhance research of disease modifying therapy.

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension.

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

Inter-individual differences in baseline dynamic functional connectivity are linked to cognitive aftereffects of tDCS.

Transcranial direct current stimulation (tDCS) has the potential to modulate cognitive training in healthy aging; however, results from various studies have been inconsistent. We hypothesized that inter-individual differences in baseline brain state may contribute to the varied results. We aimed to explore whether baseline resting-state dynamic functional connectivity (rs-dFC) and/or conventional resting-state static functional connectivity (rs-sFC) may be related to the magnitude of cognitive aftereffects of tDCS. To achieve this aim, we used data from our double-blind randomized sham-controlled cross-over tDCS trial in 25 healthy seniors in which bifrontal tDCS combined with cognitive training had induced significant behavioral aftereffects. We performed a backward regression analysis including rs-sFC/rs-dFC measures to explain the variability in the magnitude of tDCS-induced improvements in visual object-matching task (VOMT) accuracy. Rs-dFC analysis revealed four rs-dFC states. The occurrence rate of a rs-dFC state 4, characterized by a high correlation between the left fronto-parietal control network and the language network, was significantly associated with tDCS-induced VOMT accuracy changes. The rs-sFC measure was not significantly associated with the cognitive outcome. We show that flexibility of the brain state representing readiness for top-down control of object identification implicated in the studied task is linked to the tDCS-enhanced task accuracy.

Multimodal combination of neuroimaging methods for localizing the epileptogenic zone in MR-negative epilepsy.

The objective was to determine the optimal combination of multimodal imaging methods (IMs) for localizing the epileptogenic zone (EZ) in patients with MR-negative drug-resistant epilepsy. Data from 25 patients with MR-negative focal epilepsy (age 30 ± 10 years, 16M/9F) who underwent surgical resection of the EZ and from 110 healthy controls (age 31 ± 9 years; 56M/54F) were used to evaluate IMs based on 3T MRI, FDG-PET, HD-EEG, and SPECT. Patients with successful outcomes and/or positive histological findings were evaluated. From 38 IMs calculated per patient, 13 methods were selected by evaluating the mutual similarity of the methods and the accuracy of the EZ localization. The best results in postsurgical patients for EZ localization were found for ictal/ interictal SPECT (SISCOM), FDG-PET, arterial spin labeling (ASL), functional regional homogeneity (ReHo), gray matter volume (GMV), cortical thickness, HD electrical source imaging (ESI-HD), amplitude of low-frequency fluctuation (ALFF), diffusion tensor imaging, and kurtosis imaging. Combining IMs provides the method with the most accurate EZ identification in MR-negative epilepsy. The PET, SISCOM, and selected MRI-post-processing techniques are useful for EZ localization for surgical tailoring.

Differential spatial distribution of white matter lesions in Parkinson's and Alzheimer's diseases and cognitive sequelae.

White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43-87 years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer's disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson's disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42). MRI T2_FLAIR sequences were analyzed. WML were divided into periventricular (pWML) or subcortical (sWML) depending on their distance from the ventricles. Subjects from the AD + aMCI group, had a significantly greater volume of WML than both HC and the PD + PDMCI group. The volume of WML was greater in the PD + PDMCI than in HC but the difference was not significant. In AD + aMCI subjects, sWML and not pWML were related to a decrease in global cognitive functioning despite greater volume of pWML. In PD + PDMCI, pWML correlate with decline in executive functions and working memory. In HC, pWML correlated with the multidomain decrease corresponding with the aging. This points to a difference between normal aging and pathological aging due to AD and PD brain pathology. The WML location together with underlying disease related neurodegeneration may play a role in determining the effect of WML on cognition. Our results suggest that the impact of WML is not uniform in all patients; rather, their volume, location and cognitive effect may be disease-specific.

Lack of berberine effect on bone mechanical properties in rats with experimentally induced diabetes.

Multidirectional health-promoting activities of some plant-derived substances make them candidates for drugs used in diabetes and its complications such as osteoporosis. Berberine is a compound for which both antidiabetic and antiosteoporotic effects have been documented. The aim of the study was to investigate the effects of berberine on the skeletal disorders induced by experimental type 1 diabetes in rats. The experiments were performed on 3-month-old female rats, divided into three groups: I - healthy control rats, II - diabetic control rats, III - diabetic rats receiving berberine. Diabetes was induced by a single streptozotocin injection. Berberine administration (50 mg/kg/day p.o.) started two weeks later and lasted four weeks. Serum bone turnover markers and other biochemical parameters, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diabetes induced strong disorders of bone turnover, bone microarchitecture, and strength of cancellous bone. Berberine counteracted the effect of diabetes on the bone formation marker (osteocalcin) concentration, the growth plate, and some parameters of cancellous bone microarchitecture, but did not improve bone mineralization and bone mechanical properties in the diabetic rats. The lack of effect of berberine on bone quality does not support its use in the prevention of diabetes-induced bone damage.

Is the vertex a good control stimulation site? Theta burst stimulation in healthy controls.

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs. A three-dimensional finite-element model (FEM) was used to calculate the vertex TBS-induced electrical field (E-field) in the adjacent regions of interest (ROIs). Correlation analyses were performed between E-fields in the ROIs and cognitive outcomes. We found a significant effect only of the stimulation time factor (F (1,12) = 65.37, p < 0.001) on RT shortening, with no superiority of the active site stimulation compared to the vertex stimulation. In 73.5% of vertex TBS sessions, a significant E-field was induced in at least one ROI. We found a negative association between the magnitude of the iTBS-induced E-fields and RT changes (R = - 0.54, p = 0.04). TBS protocols may lead to changes in CP when applied over the craniometrically targeted vertex. We therefore suggest not using a conventional approach as a vertex targeting method.

Effects of Ovariectomy and Exercise Training on Mineral Status in a High-Fat Diet-Induced Obesity Rat Model.

Osteoporosis is a growing public health issue for an aging society. Previous studies have found both beneficial and detrimental effects of obesity on bone health. The purpose of this study was to investigate the impact of estrogen deficiency and physical activity on bone and blood concentrations of macrominerals (Ca, P, and Mg) and microminerals (Zn, Se, Cu, and Fe) in a high-fat diet-induced obesity rat model. Forty-eight female Wistar rats were divided into six groups: sham-operated and ovariectomized rats that received a standard diet (SD), high-fat diet (HFD), or HFD accompanied by physical exercise. The effect of ovariectomy on bone minerals varied with diet. Ovariectomy significantly decreased femoral Ca and Mg in sedentary rats receiving a SD; femoral Se, Cu, Zn, and Fe in sedentary rats on HFD; and plasma Fe in both sedentary rats on SD and exercising rats on HFD. The interaction of ovariectomy and diet had the strongest impact on Mg and Se concentrations in femur. In ovariectomized rats, HFD showed to have a protective effect on bone mineralization (femoral Ca and Mg), and a negative one on antioxidant microminerals (femoral Se, Cu, and Zn). Physical activity reduced the decline of Se, Cu, Zn, and Fe in the femur of ovariectomized rats on HFD. In the current state of knowledge, it is difficult to suggest if decreased femoral levels of antioxidant microminerals may contribute to the pathophysiology of osteoporosis in obese individuals or just reflect the mineral status in the body.

Contribution of the multi-echo approach in accelerated functional magnetic resonance imaging multiband acquisition.

We wanted to verify the effect of combining multi-echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi-slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole-brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single-echo (SE) data and ME data based on optimal combinations weighted by the contrast-to-noise ratio. Global metrics (temporal signal-to-noise ratio, signal-to-noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data. ME results outperformed SE results in all runs; the differences became more apparent for higher acceleration, where a significant decrease in data quality is observed. ME fMRI can improve the observed data quality metrics over SE fMRI for a wide range of accelerated fMRI acquisitions.

Current clinical practice in adapted automated peritoneal dialysis (aAPD)-A prospective, non-interventional study.

Adapted automated peritoneal dialysis (aAPD), comprising a sequence of dwells with different durations and fill volumes, has been shown to enhance both ultrafiltration and solute clearance compared to standard peritoneal dialysis with constant time and volume dwells. The aim of this non-interventional study was to describe the different prescription patterns used in aAPD in clinical practice and to observe outcomes characterizing volume status, dialysis efficiency, and residual renal function over 1 year. Prevalent and incident, adult aAPD patients were recruited during routine clinic visits, and aAPD prescription, volume status, residual renal function and laboratory data were documented at baseline and every quarter thereafter for 1 year. Treatments were prescribed according to the nephrologist's medical judgement in accordance with each center's clinical routine. Of 180 recruited patients, 160 were analyzed. 27 different aAPD prescription patterns were identified. 79 patients (49.4%) received 2 small, short dwells followed by 3 long, large dwells. During follow-up, volume status changed only marginally, with visit mean values ranging between 1.59 (95% confidence interval: 1.19; 1.99) and 1.97 (1.33; 2.61) L. Urine output and creatinine clearance decreased significantly, accompanied by reductions in ultrafiltration and Kt/V. 25 patients (15.6%) received a renal transplant and 15 (9.4%) were changed to hemodialysis. Options for individualization offered by aAPD are actually used in practice for optimized treatment. Changes observed in renal function and dialysis efficiency measures reflect the natural course of chronic kidney disease. No safety events were observed during the study period.

Modulation of Working Memory and Resting-State fMRI by tDCS of the Right Frontoparietal Network.

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.

Epileptogenic zone detection in MRI negative epilepsy using adaptive thresholding of arterial spin labeling data.

Drug-resistant epilepsy is a diagnostic and therapeutic challenge, mainly in patients with negative MRI findings. State-of-the-art imaging methods complement standard epilepsy protocols with new information and help epileptologists to increase the reliability of their decisions. In this study, we investigate whether arterial spin labeling (ASL) perfusion MRI can help localize the epileptogenic zone (EZ). To that end, we developed an image processing method to detect the EZ as an area with hypoperfusion relative to the contralateral unaffected side, using subject-specific thresholding of the asymmetry index in ASL images. We demonstrated three thresholding criteria (termed minimal product criterion, minimal distance criterion, and elbow criterion) on 29 patients with MRI-negative epilepsy (age 32.98 ± 10.4 years). The minimal product criterion showed optimal results in terms of positive predictive value (mean 0.12 in postoperative group and 0.22 in preoperative group) and true positive rate (mean 0.71 in postoperative group and 1.82 in preoperative group). Additionally, we found high accuracy in determining the EZ side (mean 0.86 in postoperative group and 0.73 in preoperative group out of 1.00). ASL can be easily incorporated into the standard presurgical MR protocol, and it provides an additional benefit in EZ localization.

A considerable proportion of metabolic syndrome-free adults from Bratislava Region, Slovakia, display an increased cardiometabolic burden.

Although the dichotomous classification of metabolic syndrome (MS) enables the classification of individuals as MS-free or presenting MS, it is inconvenient for assessing cardiometabolic risk in MS-free individuals. Continuous MS score allows for estimation of cardiometabolic burden even in MS-free subjects. We used the scores to estimate the proportion of MS-free subjects on high cardiometabolic risk. A total of 876 subjects (62% females) of Central European descent, aged 20-81 years, were included. International Diabetes Federation (IDF) criteria were employed to classify MS. Continuous scores were calculated. We used the receiver operating characteristics (ROC) analysis to estimate the cutoff value to determine the proportion of MS-free subjects on increased risk. Using the waist circumference, 38% of males and 23% of females presented MS. ROC area under the curves (90%-98%) showed an acceptable performance of both scores to classify the presence of MS. Up to 18% of MS-free males and up to 10% of females displayed continuous score ≥ the relevant cutoff point. The waist-to-height ratio performed similar results. Both continuous scores were proven credible for assessing cardiometabolic risk in MS-free subjects. Clinically, this is important for earlier intervention. Despite minor differences between waist circumference and waist-to-height ratio, it would be appropriate to objectify it using reference population. Novelty: The first study using Z-MSS/siMSS (population-specific Z-score/continuous score of MS) to estimate cardiometabolic risk in Slovak adults. A proportion of MS-free Slovak adults is on high cardiometabolic risk. Difference between using waist circumference and the waist-to-height ratio does not seem to be major in our cohort.

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy.

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [18F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy. The main benefits of ASL over PET are that it avoids radiation exposure for patients, and it offers lower costs, higher availability, and better time efficiency.

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study.

PURPOSE: People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs). METHODS: The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test. RESULTS: EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex. CONCLUSION: The two groups seem to apply different strategies for judging emotionally ambiguous stimuli, albeit resulting in equivalent judgments. We assume that activity in the supramarginal gyrus and insula in EDs is linked with suppressing their own perspective while considering emotional states, probably due to alexithymia and the lack of awareness of their own mental states. We hypothesize that the strong correlation between experienced and inferred emotions in EDs could reflect their tendency to use others as a reference point for perceiving themselves and gaining information about their affective state. LEVEL OF EVIDENCE: No level of evidence, this is a basic science study.

Brain Connectivity and Symptom Changes After Transcranial Magnetic Stimulation in Patients With Borderline Personality Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is an innovative method in the treatment of borderline personality disorder (BPD). We hypothesized that prefrontal rTMS in patients with BPD leads to improved BPD symptoms and that these effects are associated with brain connectivity changes. METHODS: Fourteen patients with BPD received 15 sessions of individually navigated prefrontal rTMS over the right dorsolateral prefrontal cortex. Clinical effects were measured by the Borderline Symptom List 23, UPPS-P, the Difficulties in Emotion Regulation Scale (DERS), the Zung Self-Rating Anxiety Scale (SAS), and the Montgomery and Åsberg Depression Rating Scale (MADRS). Effects of rTMS on brain connectivity were observed with a seed correlation analysis on resting-state fMRI and with a beta series correlation analysis on Go/No Go tasks during fMRI. Assessments were made before and immediately after the treatment. RESULTS: The assessments after rTMS showed significant reductions in two subscales of UPPS-P, and in DERS, SAS, and MADRS. The brain connectivity analysis revealed significant decreases in amygdala and insula connectivity with nodes of the posterior default mode network (pDMN; precuneus, posterior cingulate cortex, parietal lobules). Connectivity changes were observed both in the resting state and during inhibition. The decrease of amygdala-pDMN connectivity was positively correlated with reduced depression and lack of premeditation after rTMS. CONCLUSIONS: Despite the study limitations (open single-arm study in a small sample), our findings suggest a possible neural mechanism of rTMS effect in BPD, reduced amygdala connectivity with the pDMN network, which was positively associated with symptom reduction.

Social decision-making in the brain: Input-state-output modelling reveals patterns of effective connectivity underlying reciprocal choices.

During social interactions, decision-making involves mutual reciprocity-each individual's choices are simultaneously a consequence of, and antecedent to those of their interaction partner. Neuroeconomic research has begun to unveil the brain networks underpinning social decision-making, but we know little about the patterns of neural connectivity within them that give rise to reciprocal choices. To investigate this, the present study measured the behaviour and brain function of pairs of individuals (N = 66) whilst they played multiple rounds of economic exchange comprising an iterated ultimatum game. During these exchanges, both players could attempt to maximise their overall monetary gain by reciprocating their opponent's prior behaviour-they could promote generosity by rewarding it, and/or discourage unfair play through retaliation. By adapting a model of reciprocity from experimental economics, we show that players' choices on each exchange are captured accurately by estimating their expected utility (EU) as a reciprocal reaction to their opponent's prior behaviour. We then demonstrate neural responses that map onto these reciprocal choices in two brain regions implicated in social decision-making: right anterior insula (AI) and anterior/anterior-mid cingulate cortex (aMCC). Finally, with behavioural Dynamic Causal Modelling, we identified player-specific patterns of effective connectivity between these brain regions with which we estimated each player's choices with over 70% accuracy; namely, bidirectional connections between AI and aMCC that are modulated differentially by estimates of EU from our reciprocity model. This input-state-output modelling procedure therefore reveals systematic brain-behaviour relationships associated with the reciprocal choices characterising interactive social decision-making.