Background: The clinical presentation of Functional Movement Disorders (FMD) is highly variable, encompassing gait disturbances and a wide range of hyper- and hypokinetic movement abnormalities. The neurobiological correlates distinguishing different phenotypes, particularly functional gait disorders, remain poorly understood. Objective: To investigate whether functional gait disorders are associated with specific patterns of resting-state functional connectivity that distinguish them from other FMD phenotypes. Methods: Thirty-eight FMD patients (9 with isolated gait disorders, 9 with combined gait and other motor symptoms, 20 with non-gait motor symptoms) and 20 healthy controls underwent resting-state functional MRI. Using seed-based connectivity analysis with eight bilateral regions of interest of the general, non FMD-specific motor network, we examined functional connectivity patterns across groups. Results: Seed-based functional connectivity analysis revealed decreased connectivity between the left caudate nucleus and the left temporoparietal junction across gait disorder groups compared to both non-gait disorders and healthy controls. Patients with gait disorders showed decreased interhemispheric connectivity between primary sensorimotor areas compared to non-gait disorder patients, but partially increased connectivity compared to healthy controls. Both isolated and combined gait disorder groups demonstrated characteristic alterations in premotor-sensorimotor connectivity patterns, with distinct profiles between these subgroups. Conclusion: Our findings suggest distinct neurobiological signatures in functional gait disorders compared to other functional movement phenotypes. These findings might reflect specific pathophysiological mechanisms underlying functional gait disorders, particularly involving sensory feedback integration and motor control. These results provide new insights into the neurobiological basis of different FMD phenotypes and may contribute to the development of targeted therapeutic approaches.
Hypersexuality in medicated patients with PD is caused by an increased influence of motivational drive areas and a decreased influence of inhibitory control areas due to dopaminergic medication. In this pilot study, we test a newly developed paradigm investigating the influence of dopaminergic medication on brain activation elicited by sexual pictures with and without inhibitory contextual framing. Twenty PD patients with and without hypersexuality were examined with fMRI either OFF or ON standardized dopaminergic medication. The paradigm consisted of a priming phase where either a neutral context or an inhibitory context was presented. This priming phase was either followed by a sexual or a neutral target. Sexual, compared to neutral pictures resulted in a BOLD activation of various brain regions implicated in sexual processing. Hypersexual PD patients showed increased activity compared to PD controls in these regions. There was no relevant effect of medication between the two groups. The inhibitory context elicited less activation in inhibition-related areas in hypersexual PD, but had no influence on the perception of sexual cues. The paradigm partially worked: reactivity of motivational brain areas to sexual cues was increased in hypersexual PD and inhibitory contextual framing lead to decreased activation of inhibitory control areas in PD. We could not find a medication effect and the length of the inhibitory stimulus was not optimal to suppress reactivity to sexual cues. Our data provide new insights into the mechanisms of hypersexuality and warrant a replication with a greater cohort and an optimized stimulus length in the future.
ObjectiveIn this study we used functional magnetic resonance imaging (fMRI) to investigate whether motor imagery (MI) of handwriting and circle drawing activates a similar handwriting network as writing and drawing itself.MethodsEighteen healthy right-handed participants wrote the German word “Wellen” and drew continuously circles in a sitting (vertical position) and lying position (horizontal position) to capture kinematic handwriting parameters such as velocity, pressure and regularity of hand movements. Afterward, they performed the same tasks during fMRI in a MI and an executed condition.ResultsThe kinematic analysis revealed a general correlation of handwriting parameters during sitting and lying except of pen pressure during drawing. Writing compared to imagined writing was accompanied by an increased activity of the ipsilateral cerebellum and the contralateral sensorimotor cortex. Executed compared to imagined drawing revealed elevated activity of a fronto–parieto-temporal network. By contrasting writing and drawing directly, executed writing induced an enhanced activation of the left somatosensory and premotor area. The comparison of the MI of these tasks revealed a higher involvement of occipital activation during imagined writing.ConclusionThe kinematic results pointed to a high comparability of writing in a vertical and horizontal position. Overall, we observed highly overlapping cortical activity except of a higher involvement of motor control areas during motor execution. The sparse difference between writing and drawing can be explained by highly automatized writing in healthy individuals.
Background: Essential tremor (ET) occurs with steeply increasing prevalence in the elderly, and apart from disease duration, age is independently associated with an increase of tremor amplitude and a decrease of frequency. White matter hyperintensities (WMHs) are a common finding in the elderly, and their role in the pathophysiology of ET is unknown. The aims of this study were to examine whether ET patients differ in their total or region-specific WMH volumes from healthy controls and to determine the impact of WMH on tremor characteristics. Methods: A total of 47 elderly ET patients with a mean age of 72 years and 39 age-matched healthy controls underwent a thorough clinical assessment and 3T MRI. Total WMH volumes were derived from T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Additionally, region of interest-based WMH volumes for the Johns Hopkins University (JHU) white matter tracts and labels were calculated, and WMHs were assessed semiquantitatively using the Fazekas scale. Results: Essential tremor patients and healthy controls did not differ in their total or tract-specific WMH volumes or Fazekas scores. However, WMH volume was significantly positively correlated with tremor severity on the TETRAS scale, and there was a significant negative correlation with the mean accelerometric tremor frequency. In a multiple linear regression model including disease duration, age, and age-adjusted total WMH volume, only the WMH volume significantly predicted tremor severity, while age and disease duration were not significant. Conclusion: We found evidence for a direct association between WMH volume and tremor severity. If confirmed by larger studies, our findings could explain the well-known relation between age and tremor severity.
Understanding the neural correlates of risk-sensitive skin conductance responses can provide insights into their connection to emotional and cognitive processes. To provide insights into this connection, we studied the cortical correlates of risk-sensitive skin conductance peaks using electroencephalography. Fluctuations in skin conductance responses were elicited while participants played a threat-of-shock card game. Precise temporal information about skin conductance peaks was obtained by applying continuous decomposition analysis on raw electrodermal signals. Shortly preceding skin conductance peaks, we observed a decrease in oscillatory power in the frequency range between 3 and 17 Hz in occipitotemporal cortical areas. Atlas-based analysis indicated the left lingual gyrus as the source of the power decrease. The oscillatory power averaged across 3-17 Hz showed a significant negative relationship with the skin conductance peak amplitude. Our findings indicate a possible interaction between attention and threat perception. NEW & NOTEWORTHY We studied neural oscillations associated with risk-sensitive skin conductance responses. Going beyond previous studies, we applied methods with high-temporal resolution to account for the temporal properties of the sympathetic activity. Preceding skin conductance peaks, we observed decreased occipital cortex oscillatory power and a relationship between the oscillatory power decrease and the skin conductance peak amplitude. Our study suggests an interaction between attention and emotion such as threat perception reflected in skin conductance responses.
Zusammenfassung Aus einer ethnomethodologischen Perspektive werden einige grundlegende Aspekte der Urteilsbildung in sozialen Diensten vorgestellt, sowie Medien, Orte und Technologien angesprochen, die damals wie heute, zum Teil freilich mit anderen Akzenten, die Urteilsbildung in der Sozialen Arbeit prägen.
BACKGROUND:Writer's cramp (WC), a task specific form of dystonia, is considered to be a motor network disorder, but abnormal sensory tactile processing has also been acknowledged. The sensory spatial discrimination threshold (SDT) can be determined with a spatial acuity test (JVP domes). In addition to increased SDT, patients with WC exhibited dysfunctional sensory processing in the sensory cortex, insula, basal ganglia and cerebellum in a functional magnetic resonance imaging (fMRI) study while performing the spatial acuity test.OBJECTIVES:To assess whether effective connectivity (EC) in the sensory network including cortical, basal ganglia, thalamic and cerebellar regions of interest in WC patients is abnormal.METHODS:We used fMRI and applied a block design, while 19 WC patients and 13 age-matched healthy controls performed a spatial discrimination task. Before we assessed EC using dynamic causal modelling, we compared three model structures based on the current literature. We enclosed regions of interest that are established for sensory processing during right hand stimulation: Left thalamus, somatosensory, parietal and insular cortex, posterior putamen, and right cerebellum.RESULTS:The EC analysis revealed task-dependent decreased unidirectional connectivity between the insula and the posterior putamen. The connectivity involving the primary sensory cortex, parietal cortex and cerebellum were not abnormal in WC. The two groups showed no differences in their behavioural data.CONCLUSIONS:Perception and integration of sensory information requires the exchange of information between the insula cortex and the putamen, a sensory process that was disturbed in WC patients.
OBJECTIVE:Planning of voluntary object-related movements requires the estimation of the most probable object properties. We investigated how 14 writer's cramp (WC) patients compared to 14 controls use probabilistic weight cues in a serial grip-lift task.METHODS:In every grip-lift trial, an object of either light, medium or heavy weight had to be grasped and lifted after a visual cue gave a probabilistic prediction of the object weights (e.g. 32.5% light, 67.5% medium, 0 % heavy). We determined peak (1) grip force GF, (2) load force LF, (3) grip force rate GFR, (4) load force rate LFR, while we registered brain activity with functional magnetic resonance imaging.RESULTS:In both groups, GFR, LFR and GF increased when a higher probability of heavy weights was announced. When a higher probability of light weights was indicated, controls reduced GFR, LFR and GF, while WC patients did not downscale their forces. There were no inter-group differences in blood oxygenation level dependent activation.CONCLUSIONS:WC patients could not utilize the decision range in motor planning and adjust their force in a probabilistic cued fine motor task.SIGNIFICANCE:The results support the pathophysiological model of a hyperfunctional dopamine dependent direct basal ganglia pathway in WC.
Problem gamblers discount delayed rewards more rapidly than do non-gambling controls. Understanding this impulsivity is important for developing treatment options. In this article, we seek to make two contributions: First, we ask which of the currently debated economic models of intertemporal choice (exponential versus hyperbolic versus quasi-hyperbolic) provides the best description of gamblers' discounting behavior. Second, we ask how problem gamblers differ from habitual gamblers and non-gambling controls within the most favored parametrization. Our analysis reveals that the quasi-hyperbolic discounting model is strongly favored over the other two parametrizations. Within the quasi-hyperbolic discounting model, problem gamblers have both a significantly stronger present bias and a smaller long-run discount factor, which suggests that gamblers' impulsivity has two distinct sources.
Radio frequency (RF) pulses in magnetic resonance imaging (MRI) can interact with implanted devices and cause tissue damage. However, there are new devices that can safely perform measurements with liberal MRI conditions such as an RF transmission field B1+rms ≤ 2.0 μT. We investigated whether MRI in this case is limited for these technical reasons. We selected typical MRI protocols of six body regions (brain, cervical spine, lumbar spine, knee, liver, heart) using two typical 1.5T MRI scanners. Overall, we adapted 62 sequences to B1+rms conditions and evaluated their diagnostic quality. For this, we measured signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), and geometric deviation (GD) as quality parameters, using phantom studies. For questionnaire studies, we selected pairs of original and adapted sequences in healthy volunteers. Blinded radiologists rated the images as single sequence rating and in direct comparison. Roughly one-third of the checked sequences were below the B1+rms limit. Here, 56 of the 62 adapted sequences showed at least the same image quality in single ratings. A reduction in SNR and/or CNR was found with 31 sequences and only one sequence with considerably increased GD. Especially, sequences with original high B1+rms values, PD sequences, and sequences of the Siemens knee and heart protocol were difficult to adapt, whereas most TSE and IR sequences had no clinical limitations. By limiting the transmission field to B1+rms ≤ 2.0 μT, clinically relevant MR sequences can be adapted with nearly no reduction in image quality. Despite limiting the transmission field, high-quality MR imaging is possible. We could derive strategies for adaptation. • Despite limiting the transmission field, high-quality MRI is possible. • We could derive strategies for adapting the sequences to B 1+rms ≤ 2.0 μT. • This enables high-quality MRI of different body regions for patients with AD.
Objective: Multifocal epileptic activity is an unfavourable feature of a number of epileptic syndromes (Lennox-Gastaut syndrome, West syndrome, severe focal epilepsies) which suggests an overall vulnerability of the brain to pathological synchronization. However, the mechanisms of multifocal activity are insufficiently understood. This explorative study investigates whether pathological connectivity within brain areas of the default mode network as well as thalamus, brainstem and retrosplenial cortex may predispose in-dividuals to multifocal epileptic activity. Methods: 33 children suffering from multifocal and monofocal (control group) epilepsies were investigated using EEG-fMRI recordings during sleep. The blood oxygenated level dependent (BOLD) signal of 15 regions of interest was extracted and temporally correlated (resting-state functional connectivity). Results: Patients with monofocal epilepsies were characterized by strong correlations between the corresponding interhemispheric homotopic regions. This pattern of correlations with pronounced short-distance and weak long-distance functional connectivity resembles the connectivity pattern described for healthy children. Patients with multifocal epileptic activity, however, demonstrated significantly stronger correlations between a large number of regions of the default mode network as well as thalamus and brainstem, with a significant increase in long-distance connectivity compared to children with monofocal epileptic activity. In the group of patients with multifocal epilepsies there were no differences in functional connectivity between patients with or without Lennox-Gastaut syndrome. Conclusion: This explorative study shows that multifocal activity is associated with generally increased long-distance functional connectivity in the brain. It can be suggested that this pronounced connectivity may represent either a risk to pathological over synchronization or a consequence of the multifocal epileptic activity. (C) 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Functional imaging studies on decision making under uncertain risk of negative (aversive) outcomes are scarce. To get a better understanding of the underlying processes, we tested models of decision making including participants that were gambling regularly despite negative long-term consequences. Primarily, we sought to detect group differences in cortical and subcortical regions involved in decision processes. Also, we wanted to investigate, if current economic decision making models account for observable physiological data. Do we process aversive contingencies of decisions in a linear or a nonlinear manner, or both? We studied 22 pathological and 18 habitual gamblers, as well as 23 control subjects, evaluated by psychologists with a semi-structured interview and self-reported Southern Oaks Gambling Scale. Participants were scanned with blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and engaged in a card game in which un-ambiguous situations of various risk levels for punishment (unpleasant, but not painful electric shocks) were created. Apart from neural responses to punishment, our paradigm allowed us to measure how neural activity during expectation of a punishment is modulated by the probability to be punished (risk) or the certainty of the outcome (certainty). Extending previous work and testing our hypothesis, based on economic studies, we modelled expected outcomes according to the prospect theory. Activations differed spatially when situations were modelled according to risk or certainty. With linearly increasing chances of avoiding punishment we found that the BOLD signal increased in the orbitofrontal cortex, caudate nucleus, precuneus, and the posterior cingulate cortex (Fig. 1a). Conversely, with increasing certainty of an outcome (U-shaped from most certain punishment to most certain avoidance), we could demonstrate nonlinear activations in medial superior frontal cortex, anterior cingulate cortex, anterior insula and angular gyrus (Fig. 1b). Interestingly, we found no group differences in cerebral activation during the task, which dovetailed with ‘offline’ behavioural analyses of decision making in the same groups. Our results support the notion that economic decision making contains both linear and nonlinear cognitive processes largely following contingencies for risk and certainty and provide evidence that these cognitive processes are represented in different sets of brain regions. Correlates of the risk for punishment were found in areas known to be involved in dopaminergic reinforcement learning, while regions known to sub serve decision making, conflict monitoring and punishment show correlation with certainty of the outcome. While differences in reward perception in pathological gamblers are frequently described in the literature, we found no evidence for changes in punishment perception.
Referred and projecting pain can be observed in acute and chronic pain states. We present the case of a 69-year-old female patient with postherpetic neuralgia in dermatome Th2/3 who reported that touching the ipsilateral earlap (dermatome C2) would enhance pain and dynamic mechanical allodynia in the affected Th2/3-dermatome. The aim was to investigate possible underlying mechanisms of this phenomenon using the capsaicin experimental pain sensitization model, quantitative sensory testing, and functional spinal and supraspinal magnetic resonance imaging. The presented study provides evidence that a referral of pain from the ear to the trunk is possible. We discuss whether the observed phenomenon in combination with activation of pain-modulating areas on functional magnetic resonance imaging suggests either (1) a shift of descending pathways from inhibitory towards facilitating mode or (2) a deafferentation-induced reorganization of somatotopic maps, as the ear and the trunk are adjacent areas of the sensory homunculus. The results and a review about projection of pain in head-neck area are provided.
Previous studies demonstrated the influence of the post-learning period on procedural motor memory consolidation. In an early period after the acquisition, motor skills are vulnerable to modifications during wakefulness. Indeed, specific interventions such as world-list learning within this early phase of motor memory consolidation seem to enhance motor performance as an indicator for successful consolidation. This finding highlights the idea that manipulations of procedural and declarative memory systems during the early phase of memory consolidation over wakefulness may influence off-line consolidation. Using functional magnetic resonance imaging (fMRI) during initial motor sequence learning and motor sequence recall, we indirectly assess the influence of a secondary task taken place in the early phase of memory consolidation. All participants were scanned using fMRI during the learning phase of a serial reaction time task (SRTT) at 8 a.m. Afterwards, they were randomly assigned to one of five conditions. One group performed a declarative verbal, one a declarative nonverbal learning task. Two groups worked on attention tasks. A control group passed a resting condition. Participants stayed awake the whole day and performed the SRTT in the MRI scanner 12 h later at 8 p.m. At the behavioral level, the analysis of the reaction times failed to show a significant group difference. The primary analysis assessing fMRI data based on the contrast (sequence - random) between learning and retrieval also did not show any significant group differences. Therefore, our main analysis do not support the hypothesis that a secondary task influences the retrieval of the SRTT. In a more liberal fMRI analysis, we compared only the sequence blocks of the SRTT from learning to recall. BOLD signal decreased in the ipsilateral cerebellum and the supplementary motor area solely in the verbal learning group. Although our primary analysis failed to show significant changes between our groups, results of the secondary analysis could be an indication for a beneficial effect of the verbal declarative task in the early post-learning phase. A nonverbal learning task did not affect the activation within the motor network. Further studies are needed to replicate this finding and to assess the usefulness of this manipulation.
Problem gambling is a serious socioeconomic problem involving high individual and social costs. In this article, we study risk preferences of problem gamblers including their risk attitudes in the gain and loss domains, their weighting of probabilities, and their degree of loss aversion. Our findings indicate that problem gamblers are systematically more risk taking and less sensitive toward changes in probabilities in the gain domain only. Neither their risk attitudes in the loss domain nor their degree of loss aversion are significantly different from the controls. Additional evidence for a similar degree of sensitivity toward negative outcomes is gained from skin conductance data—a psychophysiological marker for emotional arousal—in a threat-of-shock task.
Previous research found increased brain responses of men with sexual interest in children (i.e., pedophiles) not only to pictures of naked children but also to pictures of child faces. This opens the possibly that pedophilia is linked (in addition to or instead of an aberrant sexual system) to an over-active nurturing system. To test this hypothesis we exposed pedophiles and healthy controls to pictures of infant and adult animals during functional magnetic resonance imaging of the brain. By using pictures of infant animals (instead of human infants), we aimed to elicit nurturing processing without triggering sexual processing. We hypothesized that elevated brain responses to nurturing stimuli will be found – in addition to other brain areas – in the anterior insula of pedophiles because this area was repeatedly found to be activated when adults see pictures of babies. Behavioral ratings confirmed that pictures of infant or adult animals were not perceived as sexually arousing neither by the pedophilic participants nor by the heathy controls. Statistical analysis was applied to the whole brain as well as to the anterior insula as region of interest. Only in pedophiles did infants relative to adult animals increase brain activity in the anterior insula, supplementary motor cortex, and dorsolateral prefrontal areas. Within-group analysis revealed an increased brain response to infant animals in the left anterior insular cortex of the pedophilic participants. Currently, pedophilia is considered the consequence of disturbed sexual or executive brain processing, but details are far from known. The present findings raise the question whether there is also an over-responsive nurturing system in pedophilia.
Background. Hypokinetic dysarthria is highly prevalent in idiopathic Parkinson disease (PD), and effectiveness of high-intensity voice treatment is well established. However, the neural correlates remain largely unknown. Objective. We aimed to specify cerebral pathophysiology of hypokinetic dysarthria and treatment-induced changes using functional magnetic resonance imaging (fMRI). Methods. We used fMRI to investigate healthy controls (HCs) and patients with idiopathic PD-associated dysarthria before and after treatment according to the Lee Silverman Voice Treatment LOUD (LSVT). During fMRI, participants covertly read sentences with normal (eg, conversation in a quiet room) or high (eg, shouting on a windy beach) intensity. In addition, we tested LSVT effects on intelligibility and different speech features (intensity, pitch, articulation). Results. LSVT effectively improved intelligibility, articulation, and pitch in patients. Covert high-intensity speech compared with covert normal-intensity speech led to increased activation of mainly secondary motor areas and bilateral superior and medial temporal regions. Prior to LSVT, patients showed less activity in several speech-associated areas compared with HCs. As a neural correlate of effective LSVT, increased right-sided superior temporal activity correlated with improved intelligibility. Conclusion. This is the first brain imaging study using a covert speech paradigm in PD, which revealed cortical hypoactivation as correlate of hypokinetic dysarthria. Furthermore, cortical correlates of effective LSVT treatment colocalized with the neuronal network, showing increased activation during high- versus normal-intensity speech generation.
Writer's cramp (WC) is a focal task-specific dystonia characterized by sustained or intermittent muscle contractions while writing, particularly with the dominant hand. Since structural lesions rarely cause WC, it has been assumed that the disease might be caused by a functional maladaptation within the sensory-motor system. Therefore, our objective was to examine the differences between patients suffering from WC and a healthy control (HC) group with regard to the effective connectivity that describes causal influences one brain region exerts over another within the motor network. The effective connectivity within a network including contralateral motor cortex (M1), supplementary motor area (SMA), globus pallidus (GP), putamen (PU) and ipsilateral cerebellum (CB) was investigated using dynamic causal modeling (DCM) for fMRI. Eight connectivity models of functional motor systems were compared. Fifteen WC patients and 18 age-matched HC performed a sequential, five-element finger-tapping task with the non-dominant and non-affected left hand within a 3 T MRI-scanner as quickly and accurately as possible. The task was conducted in a fixed block design repeated 15 times and included 30 s of tapping followed by 30 s of rest. DCM identified the same model in WC and HC as superior for reflecting basal ganglia and cerebellar motor circuits of healthy subjects. The M1-PU, as well as M1-CB connectivity, was more strongly influenced by tapping in WC, but the intracortical M1-SMA connection was more facilitating in controls. Inhibiting influences originating from GP to M1 were stronger in controls compared to WC patients whereby facilitating influences the PU exerts over CB and CB exerts over M1 were not as strong. Although the same model structure explains the given data best, DCM confirms previous research demonstrating a malfunction in effective connectivity intracortically (M1-SMA) and in the cortico-basal ganglia circuitry in WC. In addition, DCM analysis demonstrates abnormal reciprocal excitatory connectivity in the cortico-cerebellar circuitry. These results highlight the dysfunctional cerebello-cortical as well as basalganglio-cortical interaction in WC.
Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of Parasutterella sp. in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the JNK or the MC4R gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.