Reversal of Functional Brain Activity Related to Gut Microbiome and Hormones After VSG Surgery in Patients With Obesity.

CONTEXT: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. OBJECTIVE: We investigated VSG-correlated alterations of the gut-brain axis. METHODS: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis. RESULTS: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. CONCLUSION: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.

A local difference in blood-brain barrier permeability in the caudate putamen and thalamus of a rat brain induced by focused ultrasound.

A blood-brain barrier (BBB) opening induced by focused ultrasound (FUS) has been widely studied as an effective way of treating brain diseases. We investigate the effect of ultrasound's incidence angle at caudate putamen (Cp) and thalamus (Th) of the rat brain by inducing the same power of focused ultrasound that corresponds to the acoustic pressure of 0.65 MPa in free field. The BBB permeability (Ktrans) was quantitatively evaluated with dynamic contrast-enhanced magnetic resonance imaging. The group averaged (n = 11) maximum Ktrans at Cp (0.021 ± 0.012 min-1) was 1.39 times smaller than the Ktrans of Th (0.029 ± 0.01 min-1) with p = 0.00343. The group averaged (n = 6) ultrasound's incidence angles measured using the computed tomography image of rat skulls were compared with the maximum Ktrans and showed a negatively linear relation R2 = 0.7972). The maximum acoustic pressure computed from the acoustic simulation showed higher average acoustic pressures at Th (0.37 ± 0.02 MPa) compared to pressures at Cp (0.32 ± 0.01 MPa) with p = 0.138 × 10-11. More red blood cell were observed at the Th region compared to the Cp region in the tissue staining. These results indicate that localized characteristics of the sonication target within the subject should be considered for safer and more efficient BBB disruption induced by FUS.

Subcortical gray matter changes in pediatric patients with new-onset juvenile myoclonic epilepsy.

OBJECTIVE: The objective of the study was to identify the relationship between subcortical gray matter (GM) volumes and juvenile myoclonic epilepsy (JME). METHODS: We analyzed the brain magnetic resonance imaging (MRI) scans that were performed during the time of the diagnosis of epilepsy by using voxel-based morphometry (VBM) method. The volumetric three-dimensional sequence was used for structural investigation. The volumes of the thalamus, caudate nucleus, pallidum, and putamen were measured in both hemispheres of patients with JME, patients with generalized tonic-clonic seizures alone (GTCS) (as a disease control group) and healthy controls (HCs). All patients were drug-naïve, and treatment had been started after evaluating MRI results. RESULTS: Fifteen patients with JME (9 females, mean age = 16.1 ±â€¯3.2), 18 patients with GTCS (10 females, mean age = 15.5 ±â€¯2.9), and 43 HCs (24 females, mean age = 15.9 ±â€¯2.8) were included in the analysis. No significant difference was found for relative globus pallidus, caudate, and putamen volumes among the groups with JME, GTCS, and the HC group. The relative left and right thalamic volumes were significantly different between groups (Kruskal-Wallis rank test, p = 0.007, p = 0.001). In pairwise comparisons, both right and left relative thalamic volumes were lower in patients with JME than in HCs (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.597 ±â€¯0.058, p < 0.001; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.605 ±â€¯0.057, p < 0.001, Bonferroni post hoc corrections) and in patients with JME than in patients with GTCS (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.578 ±â€¯0.066, p = 0.03; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.592 ±â€¯0.068, p = 0.01, Bonferroni post hoc corrections), whereas there was no significant difference between the HCs and patients with GTCS (right thalamus: means: 0.597 ±â€¯0.058 vs. 0.578 ±â€¯0.066, p = 0.8; left thalamus: means: 0.605 ±â€¯0.057 vs. 0.592 ±â€¯0.068, p = 0.999, Bonferroni post hoc corrections). CONCLUSION: This study allowed us to know that microstructural abnormalities exist from the disease onset, and the thalamus might play a critical role in the pathogenesis of JME.

Global Functional Network Connectivity Disturbances in Parkinson's Disease with Mild Cognitive Impairment by Resting-State Functional MRI.

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson's disease (PD) with mild cognitive impairment (MCI) is a focus in resting-state functional MRI (rs-fMRI) studies. This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels: functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis. Using group independent component analysis (ICA) on rs-fMRI data acquired from 30 participants (14 healthy controls and 16 PD patients with MCI), 16 RSNs were identified, and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups. Compared to controls, patients with PD showed decreased functional connectivity within putamen network, thalamus network, cerebellar network, attention network, and self-referential network, and increased functional connectivity within execution network. Globally disturbed, mostly increased functional connectivity of FNC was observed in PD group, and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs. Cerebellar network showed decreased functional connectivity with caudate network, insular network, and self-referential network. In general, decreased functional connectivity within RSNs and globally disturbed, mostly increased functional connectivity of FNC may be characteristics of PD. Increased functional connectivity within execution network may be an early marker of PD. The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN, contributing to the understanding of the neural mechanism of PD.

Functional and structural connectivity of the executive control network in college binge drinkers.

Binge Drinking (BD) is a pattern of excessive alcohol consumption highly prevalent among college students, and has been associated with structural and functional alterations of brain networks. Recent advances in the resting-state connectivity analysis have boosted the research of the network-level connectivity disturbances associated with many psychiatric and neurological disorders, including addiction. Accordingly, atypical functional connectivity patterns in resting-state networks such as the Executive Control Network (ECN) have been found in substance users and alcohol-dependent individuals. In this study, we assessed for the first time the ECN functional and structural connectivity in a group of 34 college students, 20 (10 women) binge drinkers (BDs) in comparison with a group of 14 (8 women) alcohol abstinent controls (AACs). Overall, our findings documented increased resting-state functional connectivity (rsFC) in the BDs left middle frontal cortex of the left ECN in comparison to the AACs, while no structural connectivity differences were observed between groups. Pearson correlations revealed a positive association between the left middle frontal gyrus rsFC and the frequency of BD episodes per month, in the BD group. These findings suggest that maintaining a pattern of acute and intermittent alcohol consumption during important stages of brain development, as the transition from adolescence to adulthood, is associated with impaired ECN rsFC despite no group differences being yet noticed in the ECN structural connectivity.

Exploring the role of subcortical structures in developmental reading impairments: evidence for subgroups differentiated by caudate activity.

Although the role of cortical structures in skilled and impaired reading has been the topic of considerable investigation, the contribution of subcortical structures to reading performance is less well understood. Here, we assess the role of the caudate, putamen, and thalamus in adults with and without reading impairment. Thirty-three individuals (19 skilled readers and 14 reading impaired individuals) participated in two functional MRI tasks: (a) silent reading of real words and (b) silent reading of nonwords. Percent signal change was calculated for each of the three structures by evaluating the signal change relative to the baseline (i.e. no task or fixation crosses), and response time was measured for each reading condition. We found that for skilled readers, activity in the putamen predicted behavioral performance for both real words and nonwords. In contrast, we found evidence for two subgroups of impaired readers: a positive caudate activity group and a negative caudate activity group. Interestingly, brain activity differentially predicted reading performance depending on whether individuals had positive or negative caudate activity. We discuss our findings in the context of developmental reading impairments, print-to-speech networks, and language processing in general.

Reduced subcortical volumes among preschool-age girls and boys with ADHD.

Anomalous brain structure and function are implicated in children with attention-deficit/hyperactivity disorder (ADHD). Most neuroimaging research, however, has examined school-aged children, despite the typical onset of symptoms in early childhood. This study compared the volumes of subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) among preschoolers with ADHD and typically developing (TD) children. High resolution T1-weighted 3D MPRAGE images covering the whole brain were acquired on a 3T scanner and subcortical volumes were automatically extracted. Analyses were conducted in a total of 87 medication-naïve preschoolers, ages 4-5 years (47 with ADHD, 40 controls; 63% boys). ADHD was diagnosed using modified DSM-IV criteria based on review of developmental history, structured psychiatric interview and caregiver ratings. Compared to typically developing children, subcortical volumes were reduced among preschoolers with ADHD, with largest reductions in the caudate, globus pallidus, and thalamus. Among girls (but not boys) with ADHD, putamen and thalamus volumes were associated with ADHD symptom severity. The observed patterns of subcortical differences in preschoolers with ADHD (larger reductions in girls), contrasted with differences observed among school-aged children, (larger reductions in boys) suggests that children with ADHD show sexual dimorphism in neuroanatomical development that parallels early trajectory of symptom onset and attenuation.

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

Background: Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. Methods: 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Results: Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. Conclusion: These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia.

Increased thalamic centrality and putamen-thalamic connectivity in patients with parkinsonian resting tremor.

INTRODUCTION: Evidence has indicated a strong association between hyperactivity in the cerebello-thalamo-motor cortical loop and resting tremor in Parkinson's disease (PD). Within this loop, the thalamus serves as a central hub based on its structural centrality in the generation of resting tremor. To study whether this thalamic abnormality leads to an alteration at the whole-brain level, our study investigated the role of the thalamus in patients with parkinsonian resting tremor in a large-scale brain network context. METHODS: Forty-one patients with PD (22 with resting tremor, TP and 19 without resting tremor, NTP) and 45 healthy controls (HC) were included in this resting-state functional MRI study. Graph theory-based network analysis was performed to examine the centrality measures of bilateral thalami across the three groups. To further provide evidence to the central role of the thalamus in parkinsonian resting tremor, the seed-based functional connectivity analysis was then used to quantify the functional interactions between the basal ganglia and the thalamus. RESULTS: Compared with the HC group, patients with the TP group exhibited increased degree centrality (p < .04), betweenness centrality (p < .01), and participation coefficient (p < .01) in the bilateral thalami. Two of these alterations (degree centrality and participation coefficient) were significantly correlated with tremor severity, especially in the left hemisphere (p < .02). The modular analysis showed that the TP group had more intermodular connections between the thalamus and the regions within the cerebello-thalamo-motor cortical loop. Furthermore, the data revealed significantly enhanced functional connectivity between the putamen and the thalamus in the TP group (p = .027 corrected for family-wise error). CONCLUSIONS: These findings suggest increased thalamic centrality as a potential tremor-specific imaging measure for PD, and provide evidence for the altered putamen-thalamic interaction in patients with resting tremor.

[Neuroradiological changes by suppression of tics].

Tourette's syndrome is characterized by involuntary tics. First choice of treatment has been pharmacological, but recently, behavioural therapy teaching patients to suppress their tics has been introduced. Neuroimaging studies have shown an increased activity in the prefrontal cortex, temporal lobes and caudate nucleus, and a decreased activity in globus pallidus and putamen during inhibition of tics. The activity in the frontal lobes changes with age, probably caused by a lack of compensatory hypertrophy. In order to fully understand the mechanism behind behavioural therapy further studies are needed.

Switching between internally and externally focused attention in obsessive-compulsive disorder: Abnormal visual cortex activation and connectivity.

Obsessive-compulsive disorder (OCD) is characterized by excessive absorption with internally-generated distressing thoughts and urges, with difficulty incorporating external information running counter to their fears and concerns. In the present study, we experimentally probed this core feature of OCD through the use of a novel attention switching task that investigates transitions between internally focused (IF) and externally focused (EF) attentional states. Eighteen OCD patients and 18 controls imagined positive and negative personal event scenarios (IF state) or performed a color-word Stroop task (EF state). The IF/EF states were followed by a target detection (TD) task requiring responses to external stimuli. Compared to controls, OCD patients made significantly more errors and showed reduced activation of superior and inferior occipital cortex, thalamus, and putamen during TD following negative IF, with the inferior occipital hypoactivation being significantly greater for TD following negative IF compared to TD following the other conditions. Patients showed stronger functional connectivity between the inferior occipital region and dorsomedial prefrontal cortex. These findings point to an OCD-related impairment in the visual processing of external stimuli specifically when they follow a period of negative internal focus, and suggest that future treatments may wish to target the transition between attentional states.

Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.

Methamphetamine (Meth) use is common among HIV-infected persons. It remains unclear whether Meth dependence is associated with long-lasting degenerative changes in the brain parenchyma and microvasculature of HIV-infected individuals. We examined the postmortem brains of 78 HIV-infected adults, twenty of whom were diagnosed with lifetime Meth dependence (18 past and two current at the final follow-up visit). Using logistic regression models, we analyzed associations of Meth with cerebral gliosis (immunohistochemistry for ionized calcium-binding adapter molecule-1 (Iba1) and glial fibrillary acidic protein (GFAP) in frontal, temporo-parietal, and putamen-internal capsule regions), synaptodendritic loss (confocal microscopy for synaptophysin (SYP) and microtubule-associated protein-2 (MAP2) in frontal cortex), ß-amyloid plaque deposition (immunohistochemistry in frontal and temporo-parietal cortex and putamen), and arteriolosclerosis (histopathology in forebrain white matter). We found that Meth was associated with marked Iba1 gliosis in the temporo-parietal region (odds ratio, 4.42 (95 % confidence interval, 1.36, 14.39), p = 0.014, n = 62), which remained statistically significant after adjusting for HIV encephalitis, white matter lesions, and opportunistic diseases (n = 61); hepatitis C virus seropositivity (n = 54); and lifetime dependence on alcohol, opiates, and cannabis (n = 62). There was no significant association of Meth with GFAP gliosis, SYP or MAP2 loss, ß-amyloid plaque deposition, or arteriolosclerosis. In conclusion, we found lifetime Meth dependence to be associated with focal cerebral microgliosis among HIV-infected adults, but not with other brain degenerative changes examined. Some of the changes in select brain regions might be reversible following extended Meth abstinence or, alternatively, might have not been induced by Meth initially.

Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania.

Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related.

Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder.

Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.

Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis.

Finding the neuroanatomical correlates of prematurity is vital to understanding which structures are affected, and to designing efficient prevention and treatment strategies. Converging results reveal that thalamic abnormalities are important indicators of prematurity. However, little is known about the localization of the abnormalities within the subnuclei of the thalamus, or on the association of altered thalamic development with other deep gray matter disturbances. Here, we aim to investigate the effect of prematurity on the thalamus and the putamen in the neonatal brain, and further investigate the associated abnormalities between these two structures. Using brain structural magnetic resonance imaging, we perform a novel combined shape and pose analysis of the thalamus and putamen between 17 preterm (41.12 ± 5.08 weeks) and 19 term-born (45.51 ± 5.40 weeks) neonates at term equivalent age. We also perform a set of correlation analyses between the thalamus and the putamen, based on the surface and pose results. We locate significant alterations on specific surface regions such as the anterior and ventral anterior (VA) thalamic nuclei, and significant relative pose changes of the left thalamus and the right putamen. In addition, we detect significant association between the thalamus and the putamen for both surface and pose parameters. The regions that are significantly associated include the VA, and the anterior and inferior putamen. We detect statistically significant surface deformations and pose changes on the thalamus and putamen, and for the first time, demonstrate the feasibility of using relative pose parameters as indicators for prematurity in neonates. Our methods show that regional abnormalities of the thalamus are associated with alterations of the putamen, possibly due to disturbed development of shared pre-frontal connectivity. More specifically, the significantly correlated regions in these two structures point to frontal-subcortical pathways including the dorsolateral prefrontal-subcortical circuit, the lateral orbitofrontal-subcortical circuit, the motor circuit, and the oculomotor circuit. These findings reveal new insight into potential subcortical structural covariates for poor neurodevelopmental outcomes in the preterm population.

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the neuroanatomical substrates of ADHD have shown considerable variability. Moreover, it remains unclear whether neuroanatomical alterations linked to ADHD are also present in the unaffected siblings of those with ADHD. OBJECTIVE: To examine whether ADHD is linked to alterations in whole-brain and subcortical volumes and to study familial underpinnings of brain volumetric alterations in ADHD. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, we included participants from the large and carefully phenotyped Dutch NeuroIMAGE sample (collected from September 2009-December 2012) consisting of 307 participants with ADHD, 169 of their unaffected siblings, and 196 typically developing control individuals (mean age, 17.21 years; age range, 8-30 years). MAIN OUTCOMES AND MEASURES: Whole-brain volumes (total brain and gray and white matter volumes) and volumes of subcortical regions (nucleus accumbens, amygdala, caudate nucleus, globus pallidus, hippocampus, putamen, thalamus, and brainstem) were derived from structural magnetic resonance imaging scans using automated tissue segmentation. RESULTS: Regression analyses revealed that relative to control individuals, participants with ADHD had a 2.5% smaller total brain (ß = -31.92; 95% CI, -52.69 to -11.16; P = .0027) and a 3% smaller total gray matter volume (ß = -22.51; 95% CI, -35.07 to -9.96; P = .0005), while total white matter volume was unaltered (ß = -10.10; 95% CI, -20.73 to 0.53; P = .06). Unaffected siblings had total brain and total gray matter volumes intermediate to participants with ADHD and control individuals. Significant age-by-diagnosis interactions showed that older age was linked to smaller caudate (P < .001) and putamen (P = .01) volumes (both corrected for total brain volume) in control individuals, whereas age was unrelated to these volumes in participants with ADHD and their unaffected siblings. Attention-deficit/hyperactivity disorder was not significantly related to the other subcortical volumes. CONCLUSIONS AND RELEVANCE: Global differences in gray matter volume may be due to alterations in the general mechanisms underlying normal brain development in ADHD. The age-by-diagnosis interaction in the caudate and putamen supports the relevance of different brain developmental trajectories in participants with ADHD vs control individuals and supports the role of subcortical basal ganglia alterations in the pathophysiology of ADHD. Alterations in total gray matter and caudate and putamen volumes in unaffected siblings suggest that these volumes are linked to familial risk for ADHD.

Vertex-based morphometry in euthymic bipolar disorder implicates striatal regions involved in psychomotor function.

We hypothesized that psychomotor disturbances in patients with bipolar disorder are associated with morphometric changes in functionally specific regions of the basal ganglia and thalamus. We used structural magnetic resonance imaging and vertex-based morphometry to investigate whether psychomotor performance is associated with changes in volume and shape in euthymic subjects with bipolar disorder (n=27) compared with matched healthy controls (n=27). We saw no significant differences between age- and sex-matched groups in motor performance. We found a statistically significant group difference in the shape of the right putamen in the absence of psychomotor disturbances. There was an association between shape and motor performance in controls that was lacking in patients. We conclude that euthymic subjects with bipolar disorder without psychomotor disturbances show shape changes in regions of the right putamen that contribute to executive functions and motor function. It may be that other brain regions sustain the psychomotor functions that produce nearly identical motor performance in both groups.

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms.

BACKGROUND: Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. RESULTS: Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. CONCLUSIONS: Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.

Response inhibition in alcohol-dependent patients and patients with depression/anxiety: a functional magnetic resonance imaging study.

BACKGROUND: The inability to inhibit certain behaviors is a key feature of impulsivity, which is often present in people with a substance use disorder. However, the findings on impulsivity in people with alcohol dependence (AD) are inconsistent, possibly because of the frequent co-occurrence of depression/anxiety (D/A) and its influence on impulsivity. In the current study, we aimed to distinguish response inhibition impairments in AD from possible response inhibition effects associated with D/A. METHOD: AD patients (n = 31) with high D/A co-morbidity were compared to patients with D/A only (n = 18) and healthy controls (HCs; n = 16) using the Stop Signal Task (SST) during functional magnetic resonance imaging (fMRI). Correlation analyses were performed between activated brain areas, behavioral data and addiction and D/A characteristics. RESULTS: The three groups did not differ on response inhibition performance. However, AD severity, but not D/A severity, was positively associated with decreased response inhibition. During the SST, AD patients showed hyperactivity in the putamen and thalamus compared with D/A patients and HCs. Thalamus activation was negatively associated with AD duration. In addition, AD patients showed hypoactivity in the supplementary motor area (SMA) compared with HCs. SMA activity within HCs was negatively correlated with depressive symptom severity. Discussion In general, AD patients were not more impulsive than D/A patients or HCs but they did reveal inhibition impairments with increasing AD severity. A shift from cortical to subcortical engagement in AD patients during response inhibition may represent an alternative strategy, which decreased with longer drinking history, suggesting the presence of an AD-specific endophenotype.

Altered striatal functional connectivity in subjects with an at-risk mental state for psychosis.

Recent functional imaging work in individuals experiencing an at-risk mental state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the emergence of psychotic symptoms, contrasting with earlier findings implicating the ventral striatum. Our aims here were to characterize putative dorsal and ventral striatal circuit-level abnormalities in ARMS individuals using resting-state functional magnetic resonance imaging (fMRI) and to investigate their relationship to positive psychotic symptoms. Resting-state fMRI was acquired in 74 ARMS subjects and 35 matched healthy controls. An established method for mapping ventral and dorsal striatal functional connectivity was used to examine corticostriatal functional integrity. Positive psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental State and the Positive and Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed reductions in functional connectivity between the dorsal caudate and right dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei. ARMS subjects also showed increased functional connectivity between the ventral putamen and the insula, frontal operculum, and superior temporal gyrus bilaterally. No differences in ventral striatal (ie, nucleus accumbens) functional connectivity were found. Altered functional connectivity in corticostriatal circuits were significantly correlated with positive psychotic symptoms. Together, these results suggest that risk for psychosis is mediated by a complex interplay of alterations in both dorsal and ventral corticostriatal systems.