Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

Inactivation of posterior but not anterior dorsomedial caudate-putamen impedes learning with self-administered nicotine stimulus in male rats.

The rodent caudate-putamen is a large heterogeneous neural structure with distinct anatomical connections that differ in their control of learning processes. Previous research suggests that the anterior and posterior dorsomedial caudate-putamen (a- and p-dmCPu) differentially regulate associative learning with a non-contingent nicotine stimulus. The current study used bilateral NMDA-induced excitotoxic lesions to the a-dmCPu and p-dmCPu to determine the functional involvement of a-dmCPu and p-dmCPu in appetitive learning with contingent nicotine stimulus. Rats with a-dmCPu, p-dmCPu, or sham lesions were trained to lever-press for intravenous nicotine (0.03 mg/kg/inf) followed by access to sucrose 30 s later. After 1, 3, 9, and 20 nicotine-sucrose training sessions, appetitive learning in the form of a goal-tracking response was assessed using a non-contingent nicotine-alone test. All rats acquired nicotine self-administration and learned to retrieve sucrose from a receptacle at equal rates. However, rats with lesions to p-dmCPu demonstrated blunted learning of the nicotine-sucrose association. Our primary findings show that rats with lesions to p-dmCPu had a blunted goal-tracking response to a non-contingent nicotine administration after 20 consecutive days of nicotine-sucrose pairing. Our findings extend previous reports to a contingent model of nicotine self-administration and show that p-dmCPu is involved in associative learning with nicotine stimulus using a paradigm where rats voluntarily self-administer nicotine infusions that are paired with access to sucrose-a paradigm that closely resembles learning processes observed in humans.

Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.

BACKGROUND: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort. STUDY DESIGN: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated. RESULTS: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: ßleft = 0.56, p < 0.001; ßright = 0.65, p < 0.001, dSAT: ßleft = 0.43, p < 0.001; ßright = 0.52, p < 0.001, IAT: ßleft = 0.30, p = 0.005; ßright = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age. CONCLUSIONS: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Neuroanatomical correlates of poststroke complex regional pain syndrome: a voxel-based lesion symptom-mapping study.

Complex regional pain syndrome (CRPS) is a common poststroke complication. However, the neural substrates associated with CRPS remain unclear. We investigated the neural correlates associated with poststroke CRPS using voxel-based lesion‒symptom mapping (VLSM) analysis. Among 145 patients with ischemic stroke, 35 were diagnosed with CRPS and categorized into the poststroke CRPS group, and the remaining 110 into the control group. We compared the clinical characteristics between the groups. VLSM analysis was performed to identify the brain region associated with the development of poststroke CRPS. The clinical findings suggested that the poststroke CRPS group had lower muscle strength; lower scores on Fugl‒Meyer assessment, Manual Function Test, Mini-Mental Status Examination; and higher incidence of absent somatosensory evoked potentials in the median nerve than the control group. The head of the caudate nucleus, putamen, and white matter complexes in the corona radiata were significantly associated with poststroke CRPS development in ischemic stroke patients. These results facilitate an understanding of poststroke CRPS pathophysiology. Monitoring patients with lesions in these structures may aid the prevention and early treatment of poststroke CRPS.

Abnormal intrinsic functional network hubs in diabetic retinopathy patients.

BACKGROUND: However, whether the whole-brain functional network hub changes occur in diabetic retinopathy patients remains unknown. PURPOSE: The purpose of the study was to investigate the function network centrality and connectivity changes in diabetic retinopathy patients using the voxel-wise degree centrality method. MATERIALS AND METHODS: Thirty-four diabetic retinopathy patients (18 male and 16 female) and 38 healthy controls (18 male and 20 female) closely matched in age, sex, and education were enrolled in the study. Graph theory-based network analysis was performed to investigate the degree centrality between two groups. RESULTS: Compared with healthy controls, diabetic retinopathy patients had significantly higher degree centrality values in the pons and bilateral caudate and had significantly lower degree centrality values in the left lingual and right lingual, and right angular/middle occipital gyrus (MOG). Moreover, diabetic retinopathy patients exhibited increased functional connectivity between the bilateral lingual and right cerebellum lobe and right fusiform/bilateral caudate and increased functional connectivity between the right angular/MOG and bilateral anterior cingulum and right cuneus/bilateral precuneus and increased functional connectivity between the bilateral caudate and right lingual and right superior occipital gyrus. In contrast, diabetic retinopathy patients showed decreased functional connectivity between bilateral lingual and left lingual and right lingual and left superior occipital gyrus and decreased functional connectivity between the angular/MOG and right inferior occipital gyrus/right fusiform and left MOG/inferior occipital gyrus and decreased functional connectivity between the bilateral caudate and bilateral cerebellum crus1. CONCLUSION: Our results highlight that reorganization of the hierarchy of the cortical connectivity network related to visual network.

Neural changes following equine-assisted therapy for posttraumatic stress disorder: A longitudinal multimodal imaging study.

BACKGROUND: While effective treatments for posttraumatic stress disorder (PTSD) exist, many individuals, including military personnel and veterans fail to respond to them. Equine-assisted therapy (EAT), a novel PTSD treatment, may complement existing PTSD interventions. This study employs longitudinal neuro-imaging, including structural magnetic resonance imaging (sMRI), resting state-fMRI (rs-fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD. METHOD: Nineteen veterans with PTSD completed eight weekly group sessions of EAT undergoing multimodal MRI assessments before and after treatment. Clinical assessments were conducted at baseline, post-treatment and at 3-month follow-up. RESULTS: At post-treatment patients showed a significant increase in caudate functional connectivity (FC) and reduction in the gray matter density of the thalamus and the caudate. The increase of caudate FC was positively associated with clinical improvement seen immediately at post-treatment and at 3-month follow-up. In addition, higher baseline caudate FC was associated with greater PTSD symptom reduction post-treatment. CONCLUSIONS: This exploratory study is the first to demonstrate that EAT can affect functional and structural changes in the brains of patients with PTSD. The findings suggest that EAT may target reward circuitry responsiveness and produce a caudate pruning effect from pre- to post-treatment.

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour.

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive-compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

Neural endophenotypes and predictors of laryngeal dystonia penetrance and manifestation.

Focal dystonias are the most common forms of isolated dystonia; however, the etiopathophysiological signatures of disorder penetrance and clinical manifestation remain unclear. Using an imaging genetics approach, we investigated functional and structural representations of neural endophenotypes underlying the penetrance and manifestation of laryngeal dystonia in families, including 21 probands and 21 unaffected relatives, compared to 32 unrelated healthy controls. We further used a supervised machine-learning algorithm to predict the risk for dystonia development in susceptible individuals based on neural features of identified endophenotypes. We found that abnormalities in prefrontal-parietal cortex, thalamus, and caudate nucleus were commonly shared between patients and their unaffected relatives, representing an intermediate endophenotype of laryngeal dystonia. Machine learning classified 95.2% of unaffected relatives as patients rather than healthy controls, substantiating that these neural alterations represent the endophenotypic marker of dystonia penetrance, independent of its symptomatology. Additional abnormalities in premotor-parietal-temporal cortical regions, caudate nucleus, and cerebellum were present only in patients but not their unaffected relatives, likely representing a secondary endophenotype of dystonia manifestation. Based on alterations in the parietal cortex and caudate nucleus, the machine learning categorized 28.6% of unaffected relative as patients, indicating their increased lifetime risk for developing clinical manifestation of dystonia. The identified endophenotypic neural markers may be implemented for screening of at-risk individuals for dystonia development, selection of families for genetic studies of novel variants based on their risk for disease penetrance, or stratification of patients who would respond differently to a particular treatment in clinical trials.

White matter hyperintensities at critical crossroads for executive function and verbal abilities in small vessel disease.

The presence of white matter lesions in patients with cerebral small vessel disease (SVD) is among the main causes of cognitive decline. We investigated the relation between white matter hyperintensity (WMH) locations and executive and language abilities in 442 SVD patients without dementia with varying burden of WMH. We used Stroop Word Reading, Stroop Color Naming, Stroop Color-Word Naming, and Category Fluency as language measures with varying degrees of executive demands. The Symbol Digit Modalities Test (SDMT) was used as a control task, as it measures processing speed without requiring language use or verbal output. A voxel-based lesion-symptom mapping (VLSM) approach was used, corrected for age, sex, education, and lesion volume. VLSM analyses revealed statistically significant clusters for tests requiring language use, but not for SDMT. Worse scores on all tests were associated with WMH in forceps minor, thalamic radiations and caudate nuclei. In conclusion, an association was found between WMH in a core frontostriatal network and executive-verbal abilities in SVD, independent of lesion volume and processing speed. This circuitry underlying executive-language functioning might be of potential clinical importance for elderly with SVD. More detailed language testing is required in future research to elucidate the nature of language production difficulties in SVD.

Smaller Volume in Left-Lateralized Brain Structures Correlates with Greater Experience of Negative Non-target Emotions in Neurodegenerative Diseases.

Subjective emotional experience that is congruent with a given situation (i.e., target emotions) is critical for human survival (e.g., feeling disgusted in response to contaminated food motivates withdrawal behaviors). Neurodegenerative diseases including frontotemporal dementia and Alzheimer's disease affect brain regions critical for cognitive and emotional functioning, resulting in increased experience of emotions incongruent with the situation (i.e., non-target emotions, such as feeling happy when seeing someone grieving). We examined neuroanatomical correlates of subjective experience of non-target emotions in 147 patients with neurodegenerative diseases and 26 healthy individuals. Participants watched three films intended to elicit particular target emotions and rated their experience of negative and positive target and non-target emotions after watching each film. We found that smaller volume in left hemisphere regions (e.g., caudate, putamen, and dorsal anterior insula) was associated with greater experience of negative non-target emotions. Follow-up analyses confirmed that these effects were left-lateralized. No correlates emerged for positive non-target emotions. These findings suggest that volume loss in left-hemisphere regions produces a more diffuse, incongruent experience of non-target emotions. These findings provide a potential neuroanatomical basis for understanding how subjective emotional experience is constructed in the brain and how this can be disrupted in neurodegenerative disease.

Elevated caudate connectivity in cognitively normal Parkinson's disease patients.

Mild cognitive impairment (MCI) is common in Parkinson's disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson's patients. We recruited 18 Parkinson's disease patients-10 PDNC [normal cognition Parkinson's disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson's disease; MoCA < 26) -and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer's disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson's patient groups, but not in healthy control subjects. Interestingly, PDNC's functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer's disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson's disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson's disease. Our findings support and complement the dual syndrome hypothesis.

Differential functional dysconnectivity of caudate nucleus subdivisions in Parkinson's disease.

Caudate dopaminergic dysfunction is implied in the pathophysiology of patients with Parkinson's disease (PD). Still, connectivity specificities of the caudate nucleus (CN) subdivisions and the effect of dopamine are poorly understood. We collected MRI and neuropsychological data from 34 PD patients and 26 age- and sex-matched healthy elderly individuals (HEs) in this study. Resting-state functional connectivity analysis revealed that compared to the other CN subdivisions, the CN head was more strongly connected to the default mode network (DMN), the CN body to the frontoparietal network (FPN), and the CN tail to the visual network in HEs. PD patients off medication showed reduced connectivity within all these subdivision networks. In PD patients on medication, functional connectivity in the CN head network was significantly improved in the medial prefrontal cortex and in the body network it was improved in the dorsolateral prefrontal cortex. These improvements contributed to ameliorated motivation and cognitive function in PD patients. Our results highlighted the specific alterations and dopamine modulation in these CN subdivision networks in PD, which may provide insight into the pathophysiology and therapeutics of this disease.

Common and unique connectivity at the interface of motor, neuropsychiatric, and cognitive symptoms in Parkinson's disease: A commonality analysis.

Parkinson's disease (PD) is characterized by overlapping motor, neuropsychiatric, and cognitive symptoms. Worse performance in one domain is associated with worse performance in the other domains. Commonality analysis (CA) is a method of variance partitioning in multiple regression, used to separate the specific and common influence of collinear predictors. We apply, for the first time, CA to the functional connectome to investigate the unique and common neural connectivity underlying the interface of the symptom domains in 74 non-demented PD subjects. Edges were modeled as a function of global motor, cognitive, and neuropsychiatric scores. CA was performed, yielding measures of the unique and common contribution of the symptom domains. Bootstrap confidence intervals were used to determine the precision of the estimates and to directly compare each commonality coefficient. The overall model identified a network with the caudate nucleus as a hub. Neuropsychiatric impairment accounted for connectivity in the caudate-dorsal anterior cingulate and caudate-right dorsolateral prefrontal-right inferior parietal circuits, while caudate-medial prefrontal connectivity reflected a unique effect of both neuropsychiatric and cognitive impairment. Caudate-precuneus connectivity was explained by both unique and shared influence of neuropsychiatric and cognitive symptoms. Lastly, posterior cortical connectivity reflected an interplay of the unique and common effects of each symptom domain. We show that CA can determine the amount of variance in the connectome that is unique and shared amongst motor, neuropsychiatric, and cognitive symptoms in PD, thereby improving our ability to interpret the data while gaining novel insight into networks at the interface of these symptom domains.

Neural Insensitivity to the Effects of Hunger in Women Remitted From Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa. METHODS: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity. RESULTS: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group. CONCLUSIONS: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

Caudate reactivity to smoking cues is associated with increased responding to monetary reward in nicotine-dependent individuals.

Quitting smoking is challenging in part because environmental smoking cues can trigger the desire to smoke. Neurobiological responses to smoking cues are often observed in reward-related brain regions such as the caudate and nucleus accumbens (NAc). While reward plays a well-established role in the formation of cue reactivity, whether general reward responsiveness contributes to individual differences in cue-reactivity among chronic smokers is unclear; establishing such link could provide insight into the mechanisms maintaining cue reactivity. The current study explored this relationship by assessing smoking cue reactivity during functional magnetic imaging followed by an out-of-scanner probabilistic reward task (PRT) in 24 nicotine-dependent smokers (14 women). In addition, owing to sex differences in cue reactivity and reward function, this same relationship was examined as a function of sex. Following recent smoking, greater reward responsiveness on the PRT was associated with enhanced left caudate reactivity to smoking cues. No relationship was found in any other striatal subregion. The positive relationship between reward responsiveness and caudate smoking cue reactivity was significant only in male smokers, fitting with the idea that males and females respond to the reinforcing elements of smoking cues differently. These findings are clinically relevant as they show that, following recent smoking, nicotine-dependent individuals who are more cue reactive are also more likely to be responsive to non-drug rewards, which may be useful for making individualized treatment decisions that involve behavioral reward contingencies.

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia.

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability.

Resting-state fMRI reveals increased functional connectivity in the cerebellum but decreased functional connectivity of the caudate nucleus in Parkinson's disease.

Objective: Frequent falls are common in Parkinson's disease (PD). Resting-state fMRI (rs-fMRI) studies have found differences in functional connectivity between PD patients and healthy controls. However, whether functional connectivity in PD patients with frequent falls (PD-fallers) differs from those without falls (PD-non fallers) is unknown. Therefore, to elucidate the underlying mechanisms leading to postural instability in PD patients with frequent falls, we compared changes in functional connectivity between PD-fallers, PD-non fallers and healthy controls.Methods: Thirteen healthy controls (70.7 ± 7.2 years) were compared to thirteen PD-fallers (70.6 ± 5.9 years) and 19 PD-non fallers (71.61 ± 5.8 years) without cognitive impairment. We performed 1.5T rs-fMRI scans and evaluated gait and balance, motor symptoms and cognitive functions.Results: Cerebellar seed regions showed increased functional connectivity in PD-fallers compared to controls in two connections between the cerebellar cortex and vermis (p-value = 0.02). Conversely, in comparison to controls, functional connectivity between the precuneus and caudate nucleus was decreased in PD-non fallers (p-value = 0.015). A similar trend was also observed between controls and PD-fallers, although this difference did not reach statistical significance.Discussion: We found increased functional connectivity among cerebellar structures in PD, which may reflect an adaptive (compensatory) mechanism through activation of additional brain structures to restore gait function. In contrast, a relative disconnection between the precuneus and caudate nucleus in PD patients might indicate an impaired brain network unrelated to the risk of falls. Cerebellar areas might thus be considered as future therapeutic targets for neuromodulatory treatment of postural instability in PD.Abbreviations: DMN: default mode network; FC: functional connectivity; IPL: inferior parietal lobule; MMSE: Minimal Mental Status Examination; PD: Parkinson's disease; rs-fMRI: resting-state functional Magnetic Resonance Imaging; UPDRSIII: Unified Parkinson's disease ranking scale.