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To investigate changes in brain network organization and possible neurobehavioral similarities to attention-deficit hyperactivity disorder (ADHD), we measured changes in brain resting-state functional connectivity (rs-fMRI) and cognitive domains in patients with resistance to thyroid hormone ß (RTHß) and compared them with those in healthy control subjects. In this prospective case-control study, twenty-one participants with genetically confirmed RTHß were matched with 21 healthy controls. The Adult ADHD Self-Report Scale (ASRS-v1.1) and ADHD Rating Scale-IV were used to assess self-reported symptoms of ADHD. A voxel-wise and atlas-based approach was used to identify changes in the brain networks. The RTHß group reported behavioral symptoms similar to those of ADHD. We found evidence of weaker network integration of the lingual and fusiform gyri in the RTHß group, which was mainly driven by weaker connectivity to the bilateral insula and supplementary motor cortex. Functional connectivity between regions of the default mode network (angular gyrus/middle temporal gyrus) and regions of the cognitive control network (bilateral middle frontal gyrus) was increased in RTHß patients compared to healthy controls. Increased connectivity between regions of the default mode network and the dorsolateral prefrontal cortex is frequently reported in ADHD and is interpreted to be associated with deficits in attention. Our finding of weaker connectivity of the lingual gyrus to the bilateral insula (salience network) in RTHß patients has also been reported previously in ADHD and may reflect decreased habituation to visual stimuli and increased distractibility. Overall, our observations support the notion of neuropsychological similarities between RTHß and ADHD.

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BACKGROUND: The rubber hand illusion (RHI) is a well-established method for studying body ownership: Given adequate concordance of visual, sensory, and proprioceptive stimuli, the individual experiences a rubber hand as his or her own. OBJECTIVE: To study the effects of a threat to the rubber hand. METHODS: We created a typical RHI paradigm but added threatening pain: Both the real hand of an individual and the rubber hand were stroked with a brush, either synchronously (RHI-inducing condition) or asynchronously (control condition), but only the rubber hand was then pricked with a needle to create a threatening pain condition. Event-related potentials (ERPs) were recorded in a group of 23 typically-developed individuals. ERP effects were source-localized using low-resolution electromagnetic tomography. RESULTS: The individuals consistently reported experience of the RHI during the experiment when the brush strokes were applied synchronously to both the real hand and the rubber hand. ERP analysis revealed that synchronous brush stroking gave rise to higher amplitude of frontal ERPs in the 100-200 ms range than asynchronous brush stroking, which was interpreted as reflecting the RHI. In the threatening pain condition, ERPs showed a greater positivity at frontocentral electrodes, source localized in the supplementary motor area (SMA). CONCLUSION: SMA activation could reflect a control mechanism over reflexive motor activity, facilitating a possible threat-related response. Further studies should address ERP effects and the extent of the RHI to standard and threat stimuli in a correlative fashion to further elucidate the functional significance of the neurophysiological findings.

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Error detection in typing is crucial for assessing the adequacy of ongoing actions, leveraging both predictive mechanisms for early detection and sensory feedback for late detection. Neurophysiological studies have supported the anticipation of errors through predictive models. This research extends the understanding of error detection in typing, focusing on the neurocognitive mechanisms underlying errors in transparent and intransparent German words. Thirty-six volunteer students typed out aurally presented words, classified as either orthographically transparent or intransparent, on a computer keyboard without the possibility of correction. Because of poor spelling or excessive artifacts, the final sample comprised 27 participants. Event-related potentials (ERPs) were obtained time-locked to key presses, and behavioral data on typing correctness and speed were collected. A higher error rate and longer latency for intransparent words compared to transparent ones were found, suggesting the complexity of spelling impacts typing correctness. Post-error slowing was observed, aligning with increased cognitive control following errors. ERPs revealed a negative component akin to the error-related negativity (ERN) for typing errors, with a pronounced ERN-like negativity preceding erroneous key-presses, particularly for intransparent words. The study provides evidence of the cognitive and neural mechanisms underlying typing errors, highlighting the impact of orthographic transparency. The detection of an ERN-like negativity before erroneous key-presses, especially in typing intransparent words, underscores the brain's use of predictive mechanisms for error detection.

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BACKGROUND: Motor and vocal tics are the main symptom of Gilles de la Tourette-syndrome (GTS). A particular complex vocal tic comprises the utterance of swear words, termed coprolalia. Since taboo words are socially inappropriate, they are normally suppressed by people, which implies cognitive control processes. METHOD: To investigate the control of the unintentional pronunciation of taboo words and the associated processes of conflict monitoring, we used the "Spoonerisms of Laboratory Induced Predisposition" (SLIP) paradigm. Participants read multiple inductor word pairs with the same phonemes, followed by pronouncing a target pair with inverse phonemes. This led to a conflict between two competing speech plans: the correct word pair and the word pair with inverted phonemes. Latter speech error, a spoonerism, could result in a neutral or taboo word. We investigated 19 patients with GTS and 23 typically developed controls (TDC) and measured participants' electroencephalography (EEG) during the SLIP task. RESULTS: At the behavioral level less taboo than neutral word spoonerisms occurred in both groups without significant differences. Event-related brain potentials (ERP) revealed a difference between taboo and neutral word conditions in the GTS group at the midline electrodes in a time range of 250-400 ms after the speech prompt, which was not found in the TDC group. The extent of this effect depended on the number of inductor word pairs, suggesting an increasing level of cognitive control in the GTS group. CONCLUSION: The differences between taboo and neutral word conditions in patients with GTS compared to TDC suggest an altered recruitment of cognitive control processes in GTS, likely enlisted to suppress taboo words.

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The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

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Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.

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BACKGROUND: Patients with Parkinson's disease (PD) have been reported to exhibit unusual bouts of creativity (e.g., painting, writing), in particular in the context of treatment with dopaminergic agents. Here we investigated divergent and convergent thinking thought to underlie creativity. In addition we assessed cognitive estimation. METHOD: Twenty PD patients and 20 matched healthy control participants were subjected to the Guilford Alternate Uses task (divergent thinking), the remote associates task (convergent thinking) and two tests of cognitive estimation. RESULTS: No group differences were found for the convergent thinking task, while the Guilford Alternate Uses task revealed a decreased number of correct responses and a reduced originality for PD patients. Originality in PD was correlated to total daily dose of dopaminergic medication. Moreover, both tasks of cognitive estimation showed an impairment in PD. CONCLUSION: Only minor effects were found for psychometric indices of subprocesses of creative thinking, while estimation, relying on executive functioning, is impaired in PD. We suggest to take a product oriented view of creativity in further research on altered creative processes in PD.

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Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, theta (4-7 Hz) and alpha oscillations (8-15 Hz) had distinct functional roles. Frontal theta oscillations distinguished between new and old pairs, reflecting the inference of new information. Parietal alpha oscillations changed with serial position and symbolic distance of the pairs, representing the underlying relational structure. Frontal alpha oscillations distinguished between true and false pairs, linking the new information with the underlying relational structure. Second, theta and alpha oscillations interacted through cross-frequency and inter-regional phase synchronization. Frontal theta-alpha 1:2 phase locking appeared to coordinate spectrally diverse neural activity, enhanced for new versus old pairs and true versus false pairs. Alpha-band frontal-parietal phase coherence appeared to coordinate anatomically distributed neural activity, enhanced for new versus old pairs and false versus true pairs. It suggests that cross-frequency and inter-regional phase synchronization among theta and alpha oscillations supports human transitive inference.

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BACKGROUND: Being critical for brain development and neurocognitive function thyroid hormones may have an effect on behaviour and brain structure. Our exploratory study aimed to delineate the influence of mutations in the thyroid hormone receptor (TR) ß gene on brain structure. METHODS: High-resolution 3D T1-weighted images were acquired in 21 patients with a resistance to thyroid hormone ß (RTHß) in comparison to 21 healthy matched-controls. Changes in grey and white matter, as well as cortical thickness were evaluated using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). RESULTS: RTHß patients showed elevated circulating fT4 & fT3 with normal TSH concentrations, whereas controls showed normal thyroid hormone levels. RTHß patients revealed significantly higher scores in a self-rating questionnaire for attention deficit hyperactivity disorder (ADHD). Imaging revealed alterations of the corticospinal tract, increased cortical thickness in bilateral superior parietal cortex and decreased grey matter volume in bilateral inferior temporal cortex and thalamus. CONCLUSION: RTHb patients exhibited structural changes in multiple brain areas. Whether these structural changes are causally linked to the abnormal behavioral profile of RTHß which is similar to ADHD, remains to be determined.

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Persons with Tourette syndrome show altered social behaviours, such as echophenomena and increased personal distress in emotional situations. These symptoms may reflect an overactive mirror neuron system, causing both increased automatic imitation and a stronger tendency to share others' emotions. To test this, we measured the individual level of echophenomena with a video protocol and experimentally induced empathy for pain in 21 participants with Tourette syndrome and 25 matched controls. In the empathy for pain paradigm, pictures of hands and feet in painful or neutral situations were presented, while we measured participants' EEG and skin conductance response. Changes in somatosensory mu suppression during the observation of the pictures and pain ratings were compared between groups, and correlations were calculated with the occurrence of echophenomena, self-reported empathy and clinical measures. Our Tourette syndrome sample showed significantly more echophenomena than controls, but the groups showed no behavioural differences in empathic abilities. However, controls, but not patients with Tourette syndrome, showed the predicted increased mu suppression when watching painful compared to neutral actions. While echophenomena were present in all persons with Tourette syndrome, the hypothesis of an overactive mirror neuron system in Tourette syndrome could not be substantiated. On the contrary, the Tourette syndrome group showed a noticeable lack of mu attenuation in response to pain stimuli. In conclusion, we found a first hint of altered processing of others' emotional states in a brain region associated with the mirror neuron system.

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BACKGROUND: X-Linked dystonia-parkinsonism (XDP) is a movement disorder characterized by the presence of both dystonia and parkinsonism with one or the other more prominent in the initial stages and later on manifesting with more parkinsonian features towards the latter part of the disease. XDP patients show oculomotor abnormalities indicating prefrontal and striatal impairment. This study investigated oculomotor behavior in non-manifesting mutation carriers (NMC). We hypothesized that oculomotor disorders occur before the appearance of dystonic or parkinsonian signs. This could help to functionally identify brain regions already affected in the prodromal stage of the disease. METHODS: Twenty XDP patients, 13 NMC, and 28 healthy controls (HC) performed different oculomotor tasks typically affected in patients with parkinsonian signs. RESULTS: The error rate for two types of volitional saccades, i.e., anti-saccades and memory-guided saccades, was increased not only in XDP patients but also in NMC compared to HC. However, the increase in error rates of both saccade types were highly correlated in XDP patients only. Hypometria of reflexive saccades was only found in XDP patients. Initial acceleration and maintenance velocity of smooth pursuit eye movements were only impaired in XDP patients. CONCLUSIONS: Despite being asymptomatic, NMC already showed some oculomotor deficits reflecting fronto-striatal impairments, typically found in XDP patients. However, NMC did not show saccade hypometria and impaired smooth pursuit as seen in advanced Parkinson's disease and XDP, suggesting oculomotor state rather than trait signs in these mutation carriers. Neurodegeneration may commence in the striatum and prefrontal cortex, specifically the dorsolateral prefrontal cortex.

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BACKGROUND AND OBJECTIVE: Implicit social cognition refers to attitudes and stereotypes that may reside outside conscious awareness and control but that still affect human behavior. In particular, the implicit favoritism of an ingroup, to which an individual belongs, as opposed to an outgroup, to which the individual does not belong, characterized as ingroup bias, is of interest and is investigated here. METHOD: We used a Go/NoGo association task (GNAT) and behavioral and electroencephalographic (event-related EEG potential [ERP] analysis) measures to investigate the implicit bias toward cities in East Germany, West Germany, and Europe, in 16 individuals each from West and East Germany (mixed gender, M age = 24). The GNAT assesses an individual's Go and NoGo responses for a given association between a target category and either pole (positive or negative) of an evaluative dimension. RESULTS: Behavioral measures revealed slightly faster reaction times to the combination of European city names and negative, as compared with positive, evaluative words in both groups. ERP analysis showed an increased negativity at 400-800 ms poststimulus in the incongruent conditions of East German city/positive word pairings (in West Germans) and West German city/positive word pairings (in East Germans). CONCLUSION: An implicitly moderately negative evaluation of Europe by both groups was exhibited based on the behavioral data, and an increased level of conflict arising from the "incongruent" pairings (ie, as manifestation of an implicitly negative attitude toward East Germany in West Germans, and toward West Germany in East Germans) was exhibited based on the electrophysiological data.

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In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.

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Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.

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Daily activities such as preparing a meal rely on the ability to arrange thoughts and actions in the right order. Patients with Parkinson's disease have difficulties in sequencing tasks. Their deficits in sequential working memory have been associated with basal ganglia dysfunction. Here we demonstrate that altered parietal alpha and theta oscillations correlate with sequential working memory in Parkinson's disease. We included 15 patients with Parkinson's disease (6 women, mean age: 66.0 years), 24 healthy young (14 women, mean age: 24.1 years), and 16 older participants (7 women, mean age: 68.6 years). All participants completed a picture ordering task with scalp electroencephalogram (EEG) recording, where they arranged five pictures in a specific order and memorized them over a delay. When encoding and maintaining picture sequences, patients with Parkinson's disease showed a lower baseline alpha peak frequency with higher alpha power than healthy young and older participants. Patients with a higher baseline alpha power responded more slowly for ordered trials. When manipulating picture sequences, patients with Parkinson's disease showed a lower frequency of maximal power change for random versus ordered trials than healthy young and older participants. Healthy older participants showed a higher frequency of maximal power change than healthy young participants. Compared with patients with frequency of maximal power change in the alpha band (8-15 Hz), patients with frequency of maximal power change in the theta band (4-7 Hz) showed a higher ordering-related accuracy cost (random versus ordered) in the main task and tended to respond more slowly and less accurately in an independent working memory test. In conclusion, altered baseline alpha oscillations and task-dependent modulation of alpha and theta oscillations may be neural markers of poor sequential working memory in Parkinson's disease.

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BACKGROUND: Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease-modifying therapies at a time point where progressive neurodegeneration can still be modified. OBJECTIVES: The objective of this study was to determine whether motor or non-motor signs of the disease occur as indicators of a prodromal phase of X-linked dystonia-parkinsonism (XDP), a highly-penetrant monogenic movement disorder with striking basal ganglia pathology. METHODS: In addition to a comprehensive clinical assessment, sensor-based balance and gait analyses were performed in non-manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient-boosted trees (GBT) methodology was utilized to classify groups of interest. RESULTS: There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best-performing GBT-based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group. CONCLUSIONS: Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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BACKGROUND: Degeneration of dopaminergic neurons within the brainstem substantia nigra (SN) is both a pathological hallmark of Parkinson's disease (PD) and a major contributor to symptom expression. Therefore, non-invasive evaluation of the SN is critical for diagnosis and evaluation of disease progression. Hyperechogenicity (HE+) on midbrain transcranial sonography (TCS) supports the clinically established diagnosis of PD. Further, postmortem studies suggest involvement of neuromelanin (NM) loss and iron deposition in nigral neurodegeneration and HE+ emergence. However, the associations between HE+ and signs of nigral NM loss and iron deposition revealed by magnetic resonance imaging (MRI) have not been examined. OBJECTIVE: To elucidate the magnetic resonance- (MR-) morphological representation of the HE+ by NM-weighted (NMI) and susceptibility-weighted MRI (SWI). METHODS: Thirty-four PD patients and 29 healthy controls (HCs) received TCS followed by NMI and SWI. From MR images, two independent raters manually identified the SN, placed seeds in non-SN midbrain areas, and performed semi-automated SN segmentation with different thresholds based on seed mean values and standard deviations. Masks of the SN were then used to extract mean area, mean signal intensity, maximal signal area, maximum signal (for NMI), and minimum signal (for SWI). RESULTS: There were no significant differences in NMI- and SWI-based parameters between patients and HCs, and no significant associations between HE+ extent and NMI- or SWI-based parameters. CONCLUSION: HE+ on TCS appears unrelated to PD pathology revealed by NMI and SWI. Thus, TCS and MRI parameters should be considered complementary, and the pathophysiological correlates of the HE+ require further study.

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BACKGROUND: An increase in body weight is observed in the majority of patients with Parkinson's disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear. OBJECTIVES: To identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations. METHODS: We acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated. RESULTS: STN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images. CONCLUSIONS: Our findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

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Background: Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α, ß) with differential tissue distribution. Thyroid hormone receptor ß (TRß) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the ß form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRß on pituitary size. Methods: High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHß in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist). Results: Patients with mutant TRß (resistance to thyroid hormone ß, RTHß) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHß patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17). Conclusion: RTHß subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.

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Invasive and transcutaneous vagus nerve stimulation [(t)-VNS] have been used to treat epilepsy, depression and migraine and has also shown effects on metabolism and body weight. To what extent this treatment shapes neural networks and how such network changes might be related to treatment effects is currently unclear. Using a pre-post mixed study design, we applied either a tVNS or sham stimulation (5 h/week) in 34 overweight male participants in the context of a study designed to assess effects of tVNS on body weight and metabolic and cognitive parameters resting state (rs) fMRI was measured about 12 h after the last stimulation period. Support vector machine (SVM) classification was applied to fractional amplitude low-frequency fluctuations (fALFF) on established rs-networks. All classification results were controlled for random effects and overfitting. Finally, we calculated multiple regressions between the classification results and reported food craving. We found a classification accuracy (CA) of 79 % in a subset of four brainstem regions suggesting that tVNS leads to lasting changes in brain networks. Five of eight salience network regions yielded 76,5 % CA. Our study shows tVNS' post-stimulation effects on fALFF in the salience rs-network. More detailed investigations of this effect and their relationship with food intake seem reasonable for future studies.

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