Elevated Insulin Levels Engage the Salience Network during Multisensory Perception.

INTRODUCTION: Brain insulin reactivity has been reported in connection with systematic energy metabolism, enhancement in cognition, olfactory sensitivity, and neuroendocrine circuits. High receptor densities exist in regions important for sensory processing. The main aim of the study was to examine whether intranasal insulin would modulate the activity of areas in charge of olfactory-visual integration. METHODS: As approach, a placebo-controlled double-blind within crossover design was chosen. The experiments were conducted in a research unit of a university hospital. On separate mornings, twenty-six healthy normal-weight males aged between 19 and 31 years received either 40 IU intranasal insulin or placebo vehicle. Subsequently, they underwent 65 min of functional magnetic resonance imaging whilst performing an odor identification task. Functional brain activations of olfactory, visual, and multisensory integration as well as insulin versus placebo were assessed. Regarding the odor identification task, reaction time, accuracy, pleasantness, and intensity measurements were taken to examine the role of integration and treatment. Blood samples were drawn to control for peripheral hormone concentrations. RESULTS: Intranasal insulin administration during olfactory-visual stimulation revealed strong bilateral engagement of frontoinsular cortices, anterior cingulate, prefrontal cortex, mediodorsal thalamus, striatal, and hippocampal regions (p ≤ 0.001 familywise error [FWE] corrected). In addition, the integration contrast showed increased activity in left intraparietal sulcus, left inferior frontal gyrus, left superior frontal gyrus, and left middle frontal gyrus (p ≤ 0.013 FWE corrected). CONCLUSIONS: Intranasal insulin application in lean men led to enhanced activation in multisensory olfactory-visual integration sites and salience hubs which indicates stimuli valuation modulation. This effect can serve as a basis for understanding the connection of intracerebral insulin and olfactory-visual processing.

Conflict adaptation and related neuronal processing in Parkinson's disease.

Non-motor symptoms like cognitive impairment are a huge burden for patients with Parkinson's disease. We examined conflict adaptation by using the congruency sequence effect as an index of adaptation in 17 patients with Parkinson's disease and 18 healthy controls with an Eriksen flanker task using functional magnet resonance imaging to reveal possible differences in executive function performance. We observed overall increased response times in patients with Parkinson's disease compared to healthy controls. A flanker interference effect and congruency sequence effect occurred in both groups. A significant interaction of current and previous trial type was revealed, but no effect of response sequence concerning left or right motor responses. Therefore, top-down conflict monitoring processes are likely the main contributors leading to the congruency sequence effect in our paradigm. In both groups incongruent flanker events elicited activation in the middle temporal gyrus, inferior parietal cortex, dorsolateral prefrontal cortex and the insula in contrast to congruent flanker events. A psychophysiological interactions analysis revealed increased functional connectivity of inferior parietal cortex as a seed to the left prefrontal thalamus during incongruent vs. congruent and neutral stimuli in patients with Parkinson's disease that may reflect compensatory facilitating action selection processes. We conclude that patients with Parkinson's disease exhibit conflict adaptation comparable to healthy controls when investigated while receiving their usual medication.

Playing Tetris Lets You Rate Odors as Less Intense.

Overweight and obesity are considered a huge problem in modern societies. Previous studies have shown that people who are regularly distracted by playing videogames or watching TV while eating are more likely to be overweight and that the number of people that are gaming worldwide is rising. Further, it has been established that both, watching TV or playing video games lead to an increased snack intake and a lower rating of perceived taste intensity. Since flavor perception is accomplished not only by the sense of taste but also the sense of smell, we investigated the influence of cognitive load created by playing a video game on odor intensity perception. The participants played a low or high difficulty version of Tetris while presented with odors of food and non-food items. A higher skin conductance response (SCR) along with a decrease in task performance verified that the higher difficulty level leads to a higher cognitive load. Our behavioral data indicates a significant decrease in intensity estimates of food odors and non-food odors during the high compared to low cognitive load condition. We conclude that odor intensity estimation is influenced by real-life cognitive tasks which might in turn lead to overeating while distracted.

Functional connectivity of the motor system in dystonia due to PKAN.

PURPOSE: To demonstrate deviations of functional connectivity within the motor system in dystonic patients suffering from Pantothenate Kinase Associated Neurodegeneration, a genetic and metabolic disease, which is characterized by a primary lesion in the globus pallidus. MATERIAL AND METHODS: Functional Magnetic Resonance Imaging data were measured during resting state in 12 patients suffering from a confirmed mutation of the PANK2 gene. In this region-of-interest based analysis, data were evaluated in respect to correlation of signal time course between basal ganglia, motor-related cortical regions and cerebellum, were related to clinical data and were compared to a control group of 20 healthy volunteers. RESULTS: During resting state, correlation coefficients within the motor system were significantly lower in patients than in controls (0.025 vs. 0.133, p < 0.05). Network analysis by Network Based Statistics showed that these differences mainly affected the connectivity between a sub-network consisting of the basal ganglia and another one, the motor system-related cortical areas (p < 0.05). 6 out of 12 connections, which correlated significantly to duration of disease, were connections between both sub-networks. CONCLUSION: The finding of a reduced functional connectivity within the motor network, between the basal ganglia and cortical motor-related areas, fits well into the concept of a general functional disturbance of the motor system in PKAN.

Gender-Dependent Crossmodal Interactions Between Olfactory and Tactile Stimulation Revealed Using the Unimodal Tactile Stimulation Device (UniTaSD).

Due to the complex stimulation methods required, olfaction and touch are 2 relatively understudied senses in the field of perceptual (neuro-)science. In order to establish a consistent presentation method for the bimodal stimulation of these senses, we combined an olfactometer with the newly developed Unimodal Tactile Stimulation Device. This setup allowed us to study the influence of olfaction on tactile perception and opened up an unexplored field of research by examining the crossmodal influence of tactile stimuli on olfaction. Using a pseudorandomized design, we analyzed how positive or negative tactile and olfactory stimuli influenced the opposing modality's perceived intensity and pleasantness. By asking participants to rate tactile stimuli, we were able to reproduce previously reported differences indicating that bimodal presentation with an olfactory stimulus increases or reduces perceived tactile pleasantness in an odor-dependent manner while highlighting that this effect appears unique to women. Furthermore, we found the first evidence for the influence of tactile stimuli on perceived odor pleasantness, an effect that is also driven primarily by women in our study. Based on these findings we believe that future neurophysiological studies, using controlled stimulus presentation can help unravel how and why olfactory and tactile perception interact in the human brain.

Some like it, some do not: behavioral responses and central processing of olfactory-trigeminal mixture perception.

Exploring the potential of eucalyptol as a masking agent for aversive odors, we found that eucalyptol masks the olfactory but not the trigeminal sensation of ammonia in a previous study. Here, we further investigate the processing of a mixture consisting of eucalyptol and ammonia, two olfactory-trigeminal stimuli. We presented the two pure odors and a mixture thereof to 33 healthy participants. The nostrils were stimulated alternately (monorhinal application). We analyzed the behavioral ratings (intensity and pleasantness) and functional brain images. First, we replicated our previous finding that, within the mixture, the eucalyptol component suppressed the olfactory intensity of the ammonia component. Second, mixture pleasantness was rated differently by participants depending on which component dominated their mixture perception. Approximately half of the volunteers rated the eucalyptol component as more intense and evaluated the mixture as pleasant (pleasant group). The other half rated the ammonia component as more intense and evaluated the mixture as unpleasant (unpleasant group). Third, these individual differences were also found in functional imaging data. Contrasting the mixture either to eucalyptol or to both single odors, neural activation was found in the unpleasant group only. Activation in the anterior insula and SII was interpreted as evidence for an attentional shift towards the potentially threatening mixture component ammonia and for trigeminal enhancement. In addition to insula and SII, further regions of the pain matrix were involved when assessing all participant responses to the mixture. Both a painful sensation and an attentional shift towards the unpleasant mixture component complicates the development of an efficient mask because a pleasant perception is an important requirement for malodor coverage.

Virtual grocery shopping and cookie consumption following intranasal insulin or placebo application.

Insulin receptors are present in brain areas that are involved in the control of hunger and satiety, and intranasal insulin is assumed to have an anorexigenic effect. This known influence of insulin on satiety encouraged us to investigate the effect of intranasal insulin on feeding-related behaviors. The aim of the current study was to explore the influence of 40 IU of intranasal insulin on the grocery shopping behavior and cookie consumption in a group of 30 healthy young men, using a crossover randomized double-blind design. Using a virtual mock supermarket, we tested whether the intranasal administration of insulin influences purchase behavior in comparison to a placebo or control condition. The participants also provided hedonic ratings of food pictures, as well as their subjective feeling of hunger. We calculated an objective measure of hunger from the amount of cookies eaten. In contradiction to our hypotheses, no significant differences regarding ratings, calorie content of purchased food products, and cookie consumption were found between the treatment conditions. Our conclusion is that 40 IU intranasal insulin had no influence on the evaluation of pictured foods in healthy young men in our task. Acknowledging that previous studies have found effects for intranasal insulin and food cue processing, we suggest that future research should focus on chemosensory stimulation or cognitive tasks in behavioral experiments and carefully consider the doses of intranasal insulin. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

A Masked Aversive Odor Cannot Be Discriminated From the Masking Odor but Can Be Identified Through Odor Quality Ratings and Neural Activation Patterns.

Odor masking is a very prominent problem in our daily routines, mainly concerning unpleasant sweat or toilet odors. In the current study we explored the effectiveness of odor masking both on a behavioral and neuronal level. By definition, participants cannot differentiate a fully masked unpleasant odor from the pleasant pure odor used as a masking agent on a behavioral level. We hypothesized, however, that one can still discriminate between a fully masked odor mixture and the pure masking odor on a neuronal level and that, using a reinforcing feedback paradigm, participants could be trained to perceive this difference. A pleasant, lemon-like odor (citral) and a mixture of citral and minor amounts of an unpleasant, goat-like odor (caproic acid) were presented to participants repeatedly using a computer-controlled olfactometer and participants had to decide whether two presented stimuli were the same or different. Accuracy of this task was incentivized with a possible monetary reward. Functional imaging was used throughout the task to investigate central processing of the two stimuli. The participants rated both stimuli as isopleasant and isointense, indicating that the unpleasant odor was fully masked by the pleasant odor. The isolated caproic acid component of the mixture was rated less pleasant than the pleasant odor in a prior experimental session. Although the masked and pure stimuli were not discriminated in the forced-choice task, quality ratings on a dimensional scale differed. Further, we observed an increased activation of the insula and ventral striatum/putamen for the pure in contrast to the fully masked odor, hence revealing a difference in neuronal processing. Our hypothesis that perceptual discrimination and neuronal processing can be enhanced using a reinforcing feedback paradigm is not supported by our data.

Eucalyptol Masks the Olfactory But Not the Trigeminal Sensation of Ammonia.

Eucalyptol is a substance with rather pleasant olfactory and trigeminal characteristics and is thus suggested as an efficient tool for malodor coverage. In this study ammonia would be the malodor substance such as is found in cat litter or hair coloration. We investigated the potential of eucalyptol to inhibit both the olfactory as well as the trigeminal sensation of ammonia. For this purpose, we mixed eucalyptol and ammonia and compared odor component intensities. After being presented with either the pure odors or a binary mixture thereof, 21 young and healthy participants had to lateralize the odors and rate component (eucalyptol and ammonia) and total intensity. Analysis of intensity ratings revealed hypoadditivity (total mixture intensity was less than the sum of the total intensity of the single components). Significant interaction effects verified that mixing eucalyptol and ammonia only affected the perceived intensity of ammonia. Comparing the odor components within the pure and mixed stimuli, the ammonia component was rated as significantly less intense in the mixture compared to pure ammonia whereas the eucalyptol component was rated equal in the pure and mixed condition. On the basis of lateralization scores, we observed trigeminal mixture enhancement. We conclude that eucalyptol is a suitable masking agent to cover the unpleasant smell of ammonia; however, it fails to serve as an ammonia counterirritant because it lacks the ability to mask the trigeminal sensation of ammonia.

Odor Sensitivity After Intranasal Insulin Application Is Modulated by Gender.

Obesity constitutes a global health care problem, and often eating habits are to blame. For intervention, a thorough understanding of energy intake and expenditure is needed. In recent years, the pivotal role of insulin in connection to energy intake was established. Olfactory sensitivity may be a target of cerebral insulin action to maintain body weight. With this experiment, we aimed to explore the influence of intranasal insulin on olfactory sensitivity for the odors n-butanol and peanut in a placebo-controlled, double-blind setting in a within-subject design. All subjects participated in two experimental sessions on separate days and received either intranasal insulin or placebo in a pseudorandomized order. Application was followed by two olfactory threshold tests for n-butanol and peanut in a pseudorandomized order. After a single dose of intranasal insulin (40 IU) or placebo (0.4 ml), olfactory sensitivity for the odorants n-butanol and peanut were examined in 30 healthy normosmic participants (14 females). Measured blood parameters revealed no decrease in plasma glucose, however, insulin, leptin and cortisol levels were affected following intranasal application. Females' but not males' olfactory sensitivity for n-butanol was lower after intranasal insulin administration vs. placebo. In contrast, olfactory sensitivity for peanut was not influenced by intranasal insulin application. Our results indicate that the effects of cortical insulin levels on processing of specific odors is likely modulated by gender, as central increase of insulin concentration led to a reduced olfactory sensitivity for n-butanol in women only, which might be due to differentially regulated insulin and leptin signaling in men and women.

Semantic Congruence Alters Functional Connectivity during Olfactory-Visual Perception.

Previous research has shown that humans struggle to interpret multiple perceptual signals when the information provided by these signals is incongruent. In the context of olfactory-visual integration, behavioral and neuronal differences in response to congruent and incongruent stimulus pairs have been established. Here, we explored functional connectivity of the human brain with regard to the perception of congruent and incongruent food stimuli. Participants were simultaneously presented olfactory and visual stimuli of 4 different food objects, 2 healthy and 2 unhealthy objects. Stimulus pairs were grouped into "congruent" (olfactory and visual presentation of the same object), "semi-congruent" (stimuli of similar "healthiness"), and "incongruent" (healthy-unhealthy stimulus combination). Using functional magnetic resonance imaging and psychophysiological interaction (PPI) analyses, we revealed part of a neural network, the nodes of which show differential connectivity depending on the level of congruency of the presented stimulus combinations. This network relies strongly on, mostly left, inferior frontal gyrus. The analysis of such network transcends standard subtractive designs and indicates the need for more detailed formulations of neuronal models and increased specificity in functional imaging.

Cognitive Load Alters Neuronal Processing of Food Odors.

Obesity is a major health concern in modern societies. Although decreased physical activity and enhanced intake of high-caloric foods are important risk factors for developing obesity, human behavior during eating also plays a role. Previous studies have shown that distraction while eating increases food intake and leads to impaired processing of food stimuli. As olfaction is the most important sense involved in flavor perception, we used functional magnetic resonance imaging techniques to investigate the influence of cognitive memory load on olfactory perception and processing. Low- and high-caloric food odors were presented in combination with either low or high cognitive loads utilizing a memory task. The efficacy of the memory task was verified by a decrease in participant recall accuracy and an increase in skin conductance response during high cognitive load. Our behavioral data reveal a diminished perceived intensity for low- but not high-caloric food odors during high cognitive load. For low-caloric food odors, bilateral orbitofrontal (OFC) and piriform cortices (pirC) showed significantly lower activity during high compared with low cognitive load. For high-caloric food odors, a similar effect was established in pirC, but not in OFC. Insula activity correlates with higher intensity ratings found during the low cognitive load condition. We conclude lower activity in pirC and OFC to be responsible for diminished intensity perception, comparable to results in olfactory impaired patients and elderly. Further studies should investigate the influence of olfactory/gustatory intensities on food choices under distraction with special regards to low-caloric food.

Chemosensory danger detection in the human brain: Body odor communicating aggression modulates limbic system activation.

Although the sense of smell is involved in numerous survival functions, the processing of body odor emitted by dangerous individuals is far from understood. The aim of the study was to explore how human fight chemosignals communicating aggression can alter brain activation related to an attentional bias and danger detection. While the anterior cingulate cortex (ACC) was seen involved in processing threat-related emotional information, danger detection and error evaluation, it still remains unknown whether human chemosignals communicating aggression can potentially modulate this activation. In the fMRI experiment, healthy male and female normosmic odor recipients (n=18) completed a higher-order processing task (emotional Stroop task with the word categories anger, anxiety, happiness and neutral) while exposed to aggression and exercise chemosignals (collected from a different group of healthy male donors; n=16). Our results provide first evidence that aggression chemosignals induce a time-sensitive attentional bias in chemosensory danger detection and modulate limbic system activation. During exposure to aggression chemosignals compared to exercise chemosignals, functional imaging data indicates an enhancement of thalamus, hypothalamus and insula activation (p<.05, FWE-corrected). Together with the thalamus, the ACC was seen activated in response to threat-related words (p<.001). Chemosensory priming and habituation to body odor signals are discussed.

Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance.

tDCS modulates cortical nociceptive processing but has little to no impact on pain perception.

Transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. Several studies suggest clinical efficacy in chronic pain syndromes. However, little is known regarding its effects on cortical pain processing. In this double-blind, randomized, cross-over, sham controlled study, we examined the effects of anodal, cathodal, and sham stimulation of the left motor cortex in 16 healthy volunteers using functional imaging during an acute heat pain paradigm as well as pain thresholds, pain intensity ratings, and quantitative sensory testing. tDCS was applied at 1 mA for 15 minutes. Neither cathodal nor anodal tDCS significantly changed brain activation in response to nociceptive stimulation when compared with sham stimulation. However, contrasting the interaction of stimulation modes (anodal/cathodal) resulted in a significant decrease of activation in the hypothalamus, inferior parietal cortex, inferior parietal lobule, anterior insula, and precentral gyrus, contralateral to the stimulation site after anodal stimulation, which showed the opposite behavior after cathodal stimulation. Pain ratings and heat hyperalgesia showed only a subclinical pain reduction after anodal tDCS. Larger-scale clinical trials using higher tDCS intensities or longer durations are necessary to assess the neurophysiological effect and subsequently the therapeutic potential of tDCS.

Attention shifting in Parkinson's disease: an analysis of behavioral and cortical responses.

OBJECTIVE: The study was designed to examine persistent (input selection) versus transient (input shifting) mechanisms of attention control in Parkinson's disease (PD). METHOD: The study identifies behavioral and neural markers of selective control and shifting control using a novel combination of a flanker task with an attentional set-shifting task, and it compares patients with PD with matched controls. Event-related brain potentials (ERPs) were recorded, and analyses focused on frontally distributed N2 waves, parietally distributed P3 waves, and error-related negativities (Ne/ERN). RESULTS: Controls showed robust shifting costs (prolonged response times), but patients with PD did not show evidence for comparable shifting costs. Patients with PD made more errors than controls when required to shift between attentional sets, but also when they had to initially maintain an attentional set. At the neural level it was found that contrary to controls, patients with PD did not display any N2 and P3 augmentations on shift trials. Patients with PD further did not display any error-related activity or posterror N2 augmentation. CONCLUSIONS: Our results reveal that intact selective control and disrupted shifting control are dissociable in patients with PD, but additional work is required to dissect the proportionate effects of disease and treatment on shifting control in PD. Our ERP-based approach opens a new window onto an understanding of motor and cognitive flexibility that seems to be associated with the dopaminergic innervation of cortico-striatal loops.

Grey matter alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

BACKGROUND: Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a rare heritable disease marked by dystonia and loss of movement control. In contrast to the well-known "Eye-of-the-Tiger" sign affecting the globus pallidus, little is known about other deviations of brain morphology, especially about grey matter changes. METHODS: We investigated 29 patients with PKAN and 29 age-matched healthy controls using Magnet Resonance Imaging and Voxel-Based Morphometry. RESULTS: As compared to controls, children with PKAN showed increased grey matter density in the putamen and nucleus caudatus and adults with PKAN showed increased grey matter density in the ventral part of the anterior cingulate cortex. A multiple regression analysis with dystonia score as predictor showed grey matter reduction in the cerebellum, posterior cingulate cortex, superior parietal lobule, pars triangularis and small frontal and temporal areas and an analysis with age as predictor showed grey matter decreases in the putamen, nucleus caudatus, supplementary motor area and anterior cingulate cortex. CONCLUSIONS: The grey matter increases may be regarded as a secondary phenomenon compensating the increased activity of the motor system due to a reduced inhibitory output of the globus pallidus. With increasing age, the grey matter reduction of cortical midline structures however might contribute to the progression of dystonic symptoms due to loss of this compensatory control.

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BACKGROUND: Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. METHODS: The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. RESULTS: Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. CONCLUSIONS: This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

Absence of congruency sequence effects reveals neurocognitive inflexibility in Parkinson's disease.

The effects of Parkinson's disease (PD) on action selection in conflictual situations were examined in an experiment using the flanker task in combination with event-related brain potentials (ERPs). More specifically, we investigated the effects of PD on behavioral and neuronal indicators of both instantaneous (within-trial flanker congruency effects) and sequence-dependent (between-trial congruency sequence effects) distractor interference. Consistent with the existing literature, congruency-sensitive ERP components (i.e., fronto-central N2 and positive 'dips' of the lateralized readiness potential, LRP) were observed over medial-frontal and lateral-central regions, respectively. For situations requiring instantaneous action control, patients with PD and healthy controls showed similar congruency effects on reaction time, as well as on N2 and LRP 'dip' amplitudes. As expected, controls showed reliable congruency sequence effects on reaction time, as well as on N2 and LRP 'dip' amplitudes. However, patients with PD were completely unaffected by the congruence sequence across consecutive trials, as revealed by reaction time, as well as by N2 and LRP 'dip' amplitudes. The data imply that the effects of PD on action selection are largely restricted to a lack of adaptive modulation in time which we refer to as neurocognitive inflexibility, in the context of relatively spared abilities to instantaneously exert control over action selection. The findings are discussed in terms of basal ganglia dysfunction induced by PD which results primarily either in executive function deficits or in aberrant habit formation.

Gray matter volume reduction reflects chronic pain in trigeminal neuralgia.

Trigeminal neuralgia (TN) is supposedly caused by an ectatic blood vessel affecting the trigeminal nerve at the root entry zone of the brain stem. Recent evidence suggests an additional central component within trigeminal pain-processing in the pathophysiology of TN. Therefore, we aimed to identify specific brain regions possibly associated with the development or maintenance of TN using magnetic resonance imaging (MRI) voxel-based morphometry (VBM). Sixty patients with classical TN were compared to 49 healthy controls. Eighteen patients had TN with concomitant constant facial pain, a condition previously described as a predictor of worse treatment outcome. We found gray matter (GM) volume reduction in TN patients compared to healthy controls in the primary somatosensory and orbitofrontal cortices, as well as the in the secondary somatosensory cortex, thalamus, insula, anterior cingulate cortex (ACC), cerebellum, and dorsolateral prefrontal cortex. GM volume decrease within the ACC, parahippocampus, and temporal lobe correlated with increasing disease duration in TN. There were no differences comparing patients with and without concomitant constant facial pain. No GM increase was found comparing patient subgroups with each other and with healthy controls. The observed changes probably reflect the impact of multiple, daily attacks of trigeminal pain in these patients similar to what was previously described in other chronic pain conditions and may be interpreted as adaptation mechanism to chronic pain in regard to neuronal plasticity. The ACC, parahippocampus and temporal lobe volume reduction in parallel with disease duration may point to a pivotal role of these structures in chronic pain.