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We report the case of a 48 year old men who developed a selective impairment in famous voice recognition after ischemic stroke in right subcortical structures (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He underwent fibrinolytic treatment. During the following days he progressively recovered and was discharged without neurological focal sign. Patent foramen ovale was found. When he got back to his house he noticed that he was unable to recognize the voice of his favoured singers and needed to ask who was the singer to his relatives. Neuropsychological examination revealed a selective impairment in famous voice recognition in the absence of alteration of voice perception, face perception and famous face recognition. All other neuropsychological domains were spared. In particular language, memory and executive functions were intact. Neuroimaging carried out by means of PET and MRI revealed two small ischemic lesions in the right subcortical region, involving lenticular and caudate nuclei and in the right temporal pole. To our knowledge, this is the first case described in literature of a patient showing a selective associative phonagnosia after right anterior temporal stroke. The present case helps to clarify the brain circuits underlying famous voice recognition and adds evidence in favour of a right hemisphere involvement in processing knowledge of familiar voices. These findings are discussed in relation to current models of brain organization of person-specific and general semantic knowledge., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The present work studies the possible relation of parkinsonism and fronto-caudate dysconnectivity, as well as its relation to cognition in schizophrenia patients. We assessed parkinsonism using Simpson-Angus scale and prefronto-caudate connectivity using diffusion magnetic resonance in 22 schizophrenia patients (11 first-episodes) and 14 healthy controls. Fractional anisotropy was calculated for the white matter tracts directly linking rostral middle prefrontal (RMPF) and superior medial prefrontal (SMPF) regions with caudate nucleus. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia Scale (BACS). Total parkinsonism scores were negatively related to fractional anisotropy in the right SMPF-caudate tract in patients, which was also found in the first-episode patients alone, but not in controls. Parkinsonism was also inversely associated in patients to performance in social cognition, verbal memory, working memory and performance speed tests. In conclusion, our data support the involvement of fronto-striatal dysconnectivity in parkinsonism in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: One of the most prominent issues in a super-aging society is the rapid increase in dementia patients. Cross-sectional studies in dentistry have indicated that patients with dementia have worse oral health compared to healthy people. The purpose of this study was to clarify the influence of tooth loss on brain structure by comparing the volumes of gray matter (GM) and white matter (WM) between edentulous and dentulous subjects., Methods: Subjects were recruited from the Denture Clinic at Iwate Medical University Hospital Dental Center. Experiments were performed on edentulous (5 males, 8 females, 81.8±1.24years) and dentulous subjects (4 males, 7 females, 77.1±4.25years). Patients with dementia were excluded from this study. Brain volumes of GM and WM in edentulous and dentulous subjects were compared using intracranial volume, age, gender and history of hypertension as covariates. Analyzed brain areas were identified by transforming the Montreal Neurological Institute coordinate into the anatomical coordinate in edentulous subjects., Results: The analysis of WM structural images found no morphological differences between dentulous and edentulous subjects. However, significant atrophy of GM was observed in the hippocampus, caudate nucleus and temporal pole of the right hemisphere in edentulous subjects., Conclusions: The results of this study suggest that tooth loss was a causal factor for volume reduction in brain areas related to memory, learning and cognition., (Copyright © 2018 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.)

Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (n = 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (n = 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway.

The brain is often able to learn complex structures of the environment using a very limited amount of evidence, which is crucial for model-based planning and sequential prediction. However, little is known about the neurocomputational mechanisms of deterministic sequential prediction, as prior work has primarily focused on stochastic transition structures. Here we find that human subjects' beliefs about a sequence of states, captured by reaction times, are well explained by a Bayesian pattern-learning model that tracks beliefs about both the current state and the underlying structure of the environment, taking into account prior beliefs about possible patterns in the sequence. Using functional magnetic resonance imaging, we find distinct neural signatures of uncertainty computations on both levels. These results support the hypothesis that structure learning in the brain employs Bayesian inference., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: In schizophrenia patients the lateral ventricle enlargement has mostly been reported in relationship with smaller cortical and/or subcortical brain volumes; and it has been observed that ventricular system growth may be a consequence of the smaller caudate nucleus volume. Bicaudate parameters have been used in the Alzheimer dementia and Huntington's chorea diagnosing in order to evaluate brain changes and the enlargement of the lateral ventricles., Subjects and Methods: This study has been carried out on 140 patients out of which 70 patients (30 men and 40 women) who met the ICD 10 criteria for schizophrenia and 70 healthy controls (30 men and 40 women) matched on sex and age with the studied group. All of them underwent direct caudatometry and volume computation based on MRI scans., Results: Except for the bicorporal line, for all the parameters were obtained the statistically highly significant differences between the examined and control groups. Significant correlation was established for the majority of bicaudate parameters and volumes of the caudate nuclei and lateral ventricles., Discussion: Enlargement of the lateral ventricles is one of the most frequent MRI finding in schizophrenia patients. Ventricles are enlarging gradually and frontal horns are more affected than other parts. The increased volumes of the caudate nuclei signalized that ventricular enlargement is not the consequence of the caudate atrophy., Conclusion: Bicaudate parameters are reliable parameters for the quick orientation in order to assess the enlarged ventricles in schizophrenia patients.

Importance: Comorbidity is ubiquitous in psychiatry, but it is unclear how to differentiate neural mechanisms of co-occurring symptoms. Pediatric irritability and anxiety symptoms are prevalent and frequently co-occur. Threat orienting is pertinent to both phenotypes and is an ideal context in which to examine their unique and common neural mechanisms., Objectives: To decompose the unique and shared variances of pediatric irritability and anxiety symptoms and to determine neural correlates of these differentiated phenotypes during threat orienting., Design, Setting, and Participants: This investigation was a cross-sectional functional magnetic resonance imaging study. The setting was a research clinic at the National Institute of Mental Health. Participants were youth aged 8 to 18 years spanning multiple diagnostic categories (141 youth with disruptive mood dysregulation disorder, anxiety disorder, and/or attention-deficit/hyperactivity disorder and 56 healthy youth). This combination provided wide variation in levels of irritability and anxiety symptoms. Data were acquired between June 30, 2012, and June 28, 2016., Main Outcomes and Measures: Participants and parents rated youth's irritability on the Affective Reactivity Index and anxiety on the Screen for Child Anxiety Related Emotional Disorders. Bifactor analysis decomposed the unique and shared variances. A functional magnetic resonance imaging dot-probe task assessed attention orienting to angry (ie, threat) vs neutral faces. Whole-brain analyses examined associations between the bifactor-derived phenotypes and both neural activity and amygdala functional connectivity., Results: Among 197 participants included in the final analysis, the mean (SD) age was 13.1 (2.7) years, and 91 (46.2%) were female. The best-fit bifactor model (Comparative Fit Index, 0.959; Root Mean Square Error of Approximation, 0.066) included unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity. When the task required attention away from threat, higher parent-reported irritability was associated with increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule (t189≥4.15 for all, P < .001 for all). In contrast, higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus (t189≤-4.19 for all, P < .001 for all). These distinctive neural correlates did not emerge using a diagnostic approach., Conclusions and Relevance: A latent variable approach to parsing co-occurring symptom dimensions revealed a novel double dissociation. During orientation away from threat, only irritability was associated with neural activity, whereas only anxiety was associated with amygdala connectivity. Despite the challenges of symptom co-occurrence for clinical neuroscience, data-driven phenotyping may facilitate a path forward.

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home ( p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home ( p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes. SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use., (Copyright © 2018 the authors 0270-6474/18/385182-14$15.00/0.)

Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [ 18 F]fallypride and [ 18 F]FPEB positron emission tomography, respectively. Additionally, baseline and postalcohol glutamate and glutamine levels in the anterior cingulate cortex (ACC) were measured by using proton-magnetic resonance spectroscopy. To investigate differences in reward domains linked to both neurotransmitters, regional imaging data were related to subjective alcohol responses. Alcohol induced significant [ 18 F]fallypride displacement in the prefrontal cortex (PFC), temporal and parietal cortices and thalamus (P < 0.05, corrected for multiple comparisons). Dopamine release in the ACC and orbitofrontal and ventromedial PFCs were correlated with subjective 'liking' and 'wanting' effects (P < 0.05). In contrast, baseline mGluR5 availability was positively correlated with the 'high' effect of alcohol in dorsolateral, ventrolateral and ventromedial PFCs and in the medial temporal lobe, thalamus and caudate nucleus (P < 0.05). Although neither proton-magnetic resonance spectroscopy glutamate nor glutamine levels were affected by alcohol, baseline ACC glutamate levels were negatively associated with the alcohol 'liking' effect (P < 0.003). These data reveal new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal dopamine release may encode alcohol 'liking' and 'wanting' effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal-temporal-subcortical regions is more related to the alcohol 'high' effect., (© 2017 Society for the Study of Addiction.)

Excessive daytime sleepiness (EDS) is one of the earliest and most common non-motor symptoms of PD, substantially impacting on patient's quality of life. Using the Parkinson's Progression Markers Initiative database, we performed a case-control study to investigate whether dopaminergic deficit is associated with the development of EDS using dopaminergic specific single photon emission computed tomography (SPECT) molecular imaging of dopamine transporters (DAT). We enrolled 84 early de novo PD patients with EDS and 84 without EDS, who were matched for age, gender, age of diagnosis, years of education and disease duration. We assessed and compared semi-quantified [ 123 I]FP-CIT SPECT, and motor and non-motor features among these two groups, alongside exploring the clinical and imaging correlates of EDS and the predictive significance of these markers in the development of EDS. PD patients with EDS had worse non-motor (MDS-UPDRS Part-I, P < 0.001) and motor (MDS-UPRDS Part-II, P = 0.005) experiences of daily living, as well as worse autonomic (SCOPA-AUT, P < 0.0001) and cognitive (MoCA P = 0.05) function, depression (GDS, P = 0.002), and reduced caudate DAT ([ 123 I]FP-CIT, P = 0.024) compared to PD patients without EDS. Lower caudate [ 123 I]FP-CIT values correlated with higher EDS scores (r = -0.192, P = 0.013). Among patients without EDS, 47 PD patients (56%) developed EDS over a median follow-up of 36 months. Cox multivariate analysis, including all clinical and imaging data available, revealed that abnormal caudate [ 123 I]FP-CIT uptake (P = 0.030) and disease duration (P = 0.018) were predictors for the development of EDS. Although our findings indicate that dopaminergic deficits in the caudate may be associated to EDS in patients with PD, the pathophysiological causality is debateable, given that dopamine caudate denervation may covary with dopaminergic involvement at other targets and with non-dopaminergic involvement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI., Methods: Fifty patients with WD and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and resting-state functional MRI (rs-fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs-fMRI were determined. Asymmetry index (right or left value/left or right value) was evaluated., Results: Asymmetry of rigidity, tremor, choreic movement, and gait abnormality (asymmetry index = 1.33, 1.39, 1.36, 1.40), fiber tracts between the GP and substantia nigra (SN), GP and PU, SN and thalamus (TH), SN and cerebellum, head of the caudate nucleus (CA) and SN, PU and CA, CA and TH, TH and cerebellum (asymmetry index = 1.233, 1.260, 1.269, 1.437, 1.503, 1.138, 1.145, 1.279), CP values in the TH, SN (asymmetry index = 1.327, 1.166), ALFF values, and REHO values of the TH (asymmetry index = 1.192, 1.233) were found. Positive correlation between asymmetry index of rigidity and fiber volumes between the GP and SN, SN and TH ( r  = .221, .133, p  = .043, .036), and tremor and fiber volumes between the CA and TH ( r  = .045, p  = .040) was found., Conclusions: The neurological symptoms of patients with WD were asymmetry. The asymmetry of fiber projections may be the main cause of motor asymmetry in patients with WD.

Background: Speech recognition under noisy "cocktail-party" environments involves multiple perceptual/cognitive processes, including target detection, selective attention, irrelevant signal inhibition, sensory/working memory, and speech production. Compared to health listeners, people with schizophrenia are more vulnerable to masking stimuli and perform worse in speech recognition under speech-on-speech masking conditions. Although the schizophrenia-related speech-recognition impairment under "cocktail-party" conditions is associated with deficits of various perceptual/cognitive processes, it is crucial to know whether the brain substrates critically underlying speech detection against informational speech masking are impaired in people with schizophrenia., Methods: Using functional magnetic resonance imaging (fMRI), this study investigated differences between people with schizophrenia (n = 19, mean age = 33 ± 10 years) and their matched healthy controls (n = 15, mean age = 30 ± 9 years) in intra-network functional connectivity (FC) specifically associated with target-speech detection under speech-on-speech-masking conditions., Results: The target-speech detection performance under the speech-on-speech-masking condition in participants with schizophrenia was significantly worse than that in matched healthy participants (healthy controls). Moreover, in healthy controls, but not participants with schizophrenia, the strength of intra-network FC within the bilateral caudate was positively correlated with the speech-detection performance under the speech-masking conditions. Compared to controls, patients showed altered spatial activity pattern and decreased intra-network FC in the caudate., Conclusions: In people with schizophrenia, the declined speech-detection performance under speech-on-speech masking conditions is associated with reduced intra-caudate functional connectivity, which normally contributes to detecting target speech against speech masking via its functions of suppressing masking-speech signals.

Background and Purpose: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus., Methods: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations., Results: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P <0.001). In the ITD+ group, larger cerebral blood flow ( P =0.002) and cerebral blood volume ( P <0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch ( P =0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P >0.05). ITD had no influence on the development of subacute stroke complications., Conclusions: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials., (© 2018 American Heart Association, Inc.)

Participants of the annual World Memory Championships regularly demonstrate extraordinary memory feats, such as memorising the order of 52 playing cards in 20 s or 1000 binary digits in 5 min. On a cognitive level, memory athletes use well-known mnemonic strategies, such as the method of loci. However, whether these feats are enabled solely through the use of mnemonic strategies or whether they benefit additionally from optimised neural circuits is still not fully clarified. Investigating 23 leading memory athletes, we found volumes of their right hippocampus and caudate nucleus were stronger correlated with each other compared to matched controls; both these volumes positively correlated with their position in the memory sports world ranking. Furthermore, we observed larger volumes of the right anterior hippocampus in athletes. Complementing these structural findings, on a functional level, fMRI resting state connectivity of the anterior hippocampus to both the posterior hippocampus and caudate nucleus predicted the athletes rank. While a competitive interaction between hippocampus and caudate nucleus is often observed in normal memory function, our findings suggest that a hippocampal-caudate nucleus cooperation may enable exceptional memory performance. We speculate that this cooperation reflects an integration of the two memory systems at issue-enabling optimal combination of stimulus-response learning and map-based learning when using mnemonic strategies as for example the method of loci.

Language has been modeled as a rule governed behavior for generating an unlimited number of novel utterances using phonological, syntactic, and lexical processes. This view of language as essentially propositional is expanding as a contributory role of formulaic expressions (e.g., you know, have a nice day, how are you?) is increasingly recognized. The basic features of the functional anatomy of this language system have been described by studies of brain damage: left lateralization for propositional language and greater right lateralization and basal ganglia involvement for formulaic expressions. Positron emission tomography (PET) studies of cerebral blood flow (CBF) have established a cortical-subcortical pattern of brain activity predictive of syllable rate during phonological/lexical repetition. The same analytic approach was applied to analyzing brain images obtained during spontaneous monologues. Sixteen normal, right-handed, native English speakers underwent PET scanning during several language tasks. Speech rate for the repetition of phonological/lexical items was predicted by increased CBF in the left inferior frontal region and decreased CBF in the head of the right caudate nucleus, replicating previous results. A complementary cortical-subcortical pattern (CBF increased in the right inferior frontal region and decreased in the left caudate) was predictive of the use of speech formulas during monologue speech. The use of propositional language during the monologues was associated with strong left lateralization (increased CBF at the left inferior frontal region and decreased CBF at the right inferior frontal region). Normal communication involves the integration of two language modes, formulaic and novel, that have different neural substrates.

Objectives: Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects., Methods: Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database ( www.ppmi-info.org/data ). The study population consisted of healthy controls with screening 123 I-FP-CIT single photon emission tomography (SPECT). University of Pennsylvania Smell Identification Test (UPSIT) was assessed to evaluate the olfactory function., Results: Totally, 181 healthy subjects (117 male, 64 female) with 123 I-FP-CIT SPECT data were included in this study. Specific binding ratios (SBRs) of the caudate nucleus (rho = -0.4217, p < 0.0001), putamen (rho = -0.2292, p = 0.0019), and striatum (rho=-0.3425, p < 0.0001) showed a reduction with ageing. SBRs of the caudate nucleus, putamen, and striatum were positively correlated with UPSIT (rho = 0.3716, p < 0.0001; rho = 0.3655, p < 0.0001; rho = 0.3880, p < 0.0001). After controlling for age by partial correlation, SBRs of the caudate nucleus, putamen, and striatum showed an influence on UPSIT (rho = 0.3288, p < 0.0001; rho = 0.3374, p < 0.0001; rho = 0.3511, p < 0.0001)., Conclusion: Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects., Key Points: • Olfactory dysfunction in Parkinson's disease is prodromal to other symptoms. • The availability of dopamine transporter showed a reduction with ageing. • Olfactory function is associated with the availability of dopamine transporter.

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.

Objectives: Hypo/reduced activity in motor response inhibition (RI) cerebral networks was recently proposed as a promising specific neurobiological marker of attention deficit-hyperactivity disorder (ADHD). Before adopting such a pattern as a key diagnosis tool, we aim to replicate in an independent study the mechanisms underlying reduced RI-related activity in ADHD, after controlling for potentially confounding effects., Methods: In this fMRI study, we investigated the neural networks mediating successful and failed motor RI in children with ADHD and typically developing children (TDC) using the stop-signal task (SST) paradigm., Results: In contrast to hypofrontality predictions, children with ADHD exhibit increased neural activity during successful response inhibition in an RI-related brain network encompassing the indirect and/or hyperdirect pathways between the basal ganglia and cortex. Voxel-based morphometry analyses have further evidenced reduced grey matter volume in the left caudate in children with ADHD, which paralleled higher functional responses. Finally, connectivity analyses disclosed tighter coupling between a set of cortical regions and the right caudate as well as the right IFG, networks involved in successful RI., Conclusions: Hypo/reduced activity in RI cerebral networks in children with ADHD cannot at this time be considered as a systematic biomarker for ADHD.

Behavioral inhibition (BI) is an early temperamental profile characterized by negative reactivity to novelty, withdrawal from social situations, and increased risk for social anxiety. Previous research associated BI assessed in early childhood to striatal hypersensitivity in mid-to-late adolescence. The present study examined this association among 10 year-olds, characterized with BI at ages 24 and 36 months on measures of temperamental reactivity. Participants (n = 40) were studied at age 10 using a reward processing task during functional magnetic resonance imaging (fMRI). Child- and maternal-report of social anxiety symptoms was collected at ages 10 and 13. Findings indicate greater caudate activation and stronger striatal connectivity in high, compared to low, behaviorally inhibited children. Caudate activation related to social anxiety symptoms at both ages. These findings suggest that enhanced striatal responsivity reliably manifests among high behaviorally inhibited children as early as age 10. This may reflect hyper-sensitivity to reward or excessive motivation to avoid errors.

Stimulant abuse is disproportionately common in HIV-positive persons. Both HIV and stimulants are independently associated with deficits in reward-based decision making, but their interactive and/or additive effects are poorly understood despite their prevalent co-morbidity. Here, we examined the effects of cocaine dependence and HIV infection in 69 adults who underwent functional magnetic resonance imaging while completing an economic loss aversion task. We identified two neural networks that correlated with the evaluation of the favorable characteristics of the gamble (i.e. higher gains/lower losses: ventromedial prefrontal cortex, anterior cingulate, anterior and posterior precuneus and visual cortex) versus unfavorable characteristics of the gamble (i.e. lower gains/higher losses: dorsal prefrontal, lateral orbitofrontal, posterior parietal cortex, anterior insula and dorsal caudate). Behaviorally, cocaine and HIV had additive effects on loss aversion scores, with HIV-positive cocaine users being the least loss averse. Cocaine users had greater activation in brain regions that tracked the favorability of gamble characteristics (i.e. increased activation to gains, but decreased activation to losses). In contrast, HIV infection was independently associated with lesser activation in regions that tracked the unfavorability of gamble characteristics. These results suggest that cocaine is associated with an overactive reward-seeking system, while HIV is associated with an underactive cognitive control system. Together, these alterations may leave HIV-positive cocaine users particularly vulnerable to making unfavorable decisions when outcomes are uncertain., (© 2017 Society for the Study of Addiction.)

Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood., (© 2017 Society for the Study of Addiction.)

During sentence processing, areas of the left superior temporal sulcus, inferior frontal gyrus and left basal ganglia exhibit a systematic increase in brain activity as a function of constituent size, suggesting their involvement in the computation of syntactic and semantic structures. Here, we asked whether these areas play a universal role in language and therefore contribute to the processing of non-spoken sign language. Congenitally deaf adults who acquired French sign language as a first language and written French as a second language were scanned while watching sequences of signs in which the size of syntactic constituents was manipulated. An effect of constituent size was found in the basal ganglia, including the head of the caudate and the putamen. A smaller effect was also detected in temporal and frontal regions previously shown to be sensitive to constituent size in written language in hearing French subjects (Pallier et al., 2011). When the deaf participants read sentences versus word lists, the same network of language areas was observed. While reading and sign language processing yielded identical effects of linguistic structure in the basal ganglia, the effect of structure was stronger in all cortical language areas for written language relative to sign language. Furthermore, cortical activity was partially modulated by age of acquisition and reading proficiency. Our results stress the important role of the basal ganglia, within the language network, in the representation of the constituent structure of language, regardless of the input modality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To compare transcranial sonography (TCS) findings in patients with predominantly neurological Wilson's disease (WD) to those from controls, and to correlate TCS data with the clinical profile of WD. Patients with WD (n=40/f=18) and healthy, matched controls (n=49/f=20) were assessed in terms of TCS, serum copper and iron parameters, and clinical scales, such as the Unified Wilson's Disease Rating Scale (UWDRS), Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Mental State Examination (MMSE), and Beck Depression Inventory. Lenticular nuclei and substantia nigra echogenic area cut-off values clearly differentiated WD patients from controls (area under the curve: 95.4% and 79.4%). Substantia nigra echogenic area was significantly larger in male than in female patients (p=0.001). Compared with controls, patients showed hyperechogenicity also in thalami and midbrain tegmentum/tectum; third ventricle width was increased and midbrain axial area was reduced. In the WD group, male gender correlated with substantia nigra echogenic area (r=0.515, p=0.0007) and serum ferritin levels (r=0.479, p=0.002); lenticular nuclei hyperechogenicity correlated with dystonia (r=0.326, p=0.04) and dysarthria (r=0.334, p=0.035); third ventricle width correlated with dystonia (r=0.439 p=0.005), dysarthria (r=0.449, p=0.004), parkinsonism (r=0.527, p<0.001), UWDRS neurological and total scores (both r=0.504, p=0.0009), MMSE (r=-0.496, p=0.001), and ACE-R (r=-0.534, p=0.0004). Lenticular nuclei echogenic area allowed highly accurate discrimination between patients and controls. The gender differences in substantia nigra echogenicity and iron metabolism are of interest in further studies in WD. TCS reflects different dimensions of WD pathology clearly differentiable from healthy controls and correlating with various clinical characteristics of WD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: In the present study, we used Activation Likelihood Estimation (ALE) meta-analysis to quantitatively examine brain grey matter reduction in schizophrenia patients with persistent negative symptoms (PNS)., Method: A total of 12 voxel-based morphometry (VBM) studies were included in ALE meta-analysis using more stringent criterion of PNS., Results: Significant grey matter reduction in the PNS group relative to controls was observed in the left caudate nucleus, the left precentral region, the left middle frontal region, the bilateral parahippocampal region, the left anterior cingulate region, the bilateral medial frontal gyrus, the thalamus and the insula., Conclusion: Our results suggest that brain regions in the reward network may be specifically related to PNS, especially the left caudate nucleus. It is possible that abnormality in reward processing may constitute the neural basis of PNS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP., Methods: We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in 18 F-FP-CIT positron emission tomography scans. According to their exposure durations to the offending drugs prior to onset of the parkinsonism, the patients were divided into the early-onset group (duration ≤6 months; n=35) and delayed-onset group (duration >6 months; n=36). We performed the quantitative analysis of the DAT availability in each striatal subregion between the groups., Results: No patients with DIP had DAT availability that was more than 2 SD below the normal mean of DAT availability. Compared with the delayed-onset group, the early-onset DIP group had decreased DAT availability in the striatal subregions including the posterior putamen (p=0.018), anterior putamen (p=0.011), caudate (p=0.035) and ventral striatum (p=0.027). After adjusting for age, sex and cross-cultural smell identification test scores, a multivariate analysis revealed that the DAT availability in the striatal subregions of the patients with DIP was significantly and positively associated with the natural logarithm of the duration of drug exposure., Conclusions: These results suggest that a short exposure to the offending drugs before the development of parkinsonism would be associated with subtle nigrostriatal dopaminergic dysfunction in patients with DIP., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: A recently published study using an automated MRI volumetry method (NeuroQuant®) unexpectedly demonstrated larger caudate nucleus volume in patients with Alzheimer's disease dementia (AD) compared to patients with subjective and mild cognitive impairment (SCI and MCI). The aim of this study was to explore this finding., Materials & Methods: The caudate nucleus and the hippocampus volumes were measured (both expressed as ratios of intracranial volume) in a total of 257 patients with SCI and MCI according to the Winblad criteria and AD according to ICD-10 criteria. Demographic data, cognitive measures, and APOE-ɛ4 status were collected., Results: Compared with non-dementia patients (SCI and MCI), AD patients were older, more of them were female, and they had a larger caudate nucleus volume and smaller hippocampus volume (P<.001). In multiple linear regression analysis, age and female sex were associated with larger caudate nucleus volume, but neither diagnosis nor memory function was. Age, gender, and memory function were associated with hippocampus volume, and age and memory function were associated with caudate nucleus/hippocampus ratio., Conclusions: A larger caudate nucleus volume in AD patients was partly explained by older age and being female. These results are further discussed in the context of (1) the caudate nucleus possibly serving as a mechanism for temporary compensation; (2) methodological properties of automated volumetry of this brain region; and (3) neuropathological alterations. Further studies are needed to fully understand the role of the caudate nucleus in AD., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To provide whole brain grey matter (GM) to white matter (WM) contrast enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM), proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted imaging (SWI), and R2* maps with minimal misregistration in scanning times <5min., Methods: Strategically acquired gradient echo (STAGE) imaging includes two fully flow compensated double echo gradient echo acquisitions with a resolution of 0.67×1.33×2.0mm 3 acquired in 5min for 64 slices. Ten subjects were recruited and scanned at 3 Tesla. The optimum pair of flip angles (6° and 24° with TR=25ms at 3T) were used for both T1 mapping with radio frequency (RF) transmit field correction and creating enhanced GM/WM contrast (the T1WE). The proposed T1WE image was created from a combination of the proton density weighted (6°, PDW) and T1W (24°) images and corrected for RF transmit field variations. Prior to the QSM calculation, a multi-echo phase unwrapping strategy was implemented using the unwrapped short echo to unwrap the longer echo to speed up computation. R2* maps were used to mask deep grey matter and veins during the iterative QSM calculation. A weighted-average sum of susceptibility maps was generated to increase the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR)., Results: The proposed T1WE image has a significantly improved CNR both for WM to deep GM and WM to cortical GM compared to the acquired T1W image (the first echo of 24° scan) and the T1MPRAGE image. The weighted-average susceptibility maps have 80±26%, 55±22%, 108±33% SNR increases across the ten subjects compared to the single echo result of 17.5ms for the putamen, caudate nucleus, and globus pallidus, respectively., Conclusions: STAGE imaging offers the potential to create a standardized brain imaging protocol providing four pieces of quantitative tissue property information and multiple types of qualitative information in just 5min., (Published by Elsevier Inc.)

The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: Bipolar disorder (BD) and schizophrenia (SZ) share structural abnormalities in the anterior insula cortex (AIC). The AIC appears to have a crucial role in emotional processing and regulation and cognitive control in BD and SZ., Methods: Forty-six participants with BD, 68 with SZ and 66 healthy controls (HC) underwent functional magnetic resonance imaging scanning. Resting-state functional connectivity (rsFC) from AIC subregions (ventral and dorsal) was compared among the three groups., Results: Compared to HC group, both BD and SZ groups exhibited increased rsFC from the ventral AIC (vAIC) and dorsal AIC (dAIC) to bilateral frontal pole and thalamus, the left middle frontal gyrus and the hippocampus. Meanwhile, the BD group demonstrated increased rsFC from the vAIC to the perigenual anterior cingulate cortex, the SZ group presented increased rsFC from the vAIC and dAIC to the right caudate. Compared with the BD group, the SZ group showed significantly increased rsFC from the vAIC and dAIC to the left middle frontal gyrus., Conclusions: The shared AIC rsFC abnormalities in both BD and SZ support the importance of the AIC in the common pathophysiology of BD and SZ. There were also disorder-specific features of AIC rsFC, which might implicate potential avenues for differentiating during the early stages.

Background: Mild Parkinsonian signs (MPS) are commonly seen in aging, and have been related to cerebral Small Vessel Diseases (SVD) with no univocal results., Objective: The aim of this study was to investigate the cross-sectional relation between MPS and White Matter Hyperintensities (WMH), lacunes, caudate atrophy, and global cerebral atrophy in a large cohort of Neurologically and Cognitively Healthy (NCH) aging individuals., Method: 1,219 NCH individuals were included in the analysis, and underwent standard brain MRI. The items of the motor section of the Unified Parkinson's Disease Rating Scale were used to evaluate tremor, rigidity, bradykinesia, and gait/balance/axial dysfunction. Caudate atrophy and global cerebral atrophy were assessed through the bicaudate ratio and the lateral ventricles to brain ratio, respectively. WMH were assessed through two visual rating scales. Lacunes were also rated. Associations of MPS with vascular risk factors/diseases and imaging findings were determined through the logistic regression analysis., Results: Frontal and basal ganglia lacunes, frontal WMH, caudate atrophy, and global cerebral atrophy were associated with bradykinesia. Basal ganglia lacunes, caudate atrophy, and global cerebral atrophy were associated with gait/balance/axial dysfunction. Rigidity was associated with frontal WMH, and tremor with caudate atrophy and global cerebral atrophy. NCH subjects with MPS, performed less than subjects without MPS in tests evaluating global cognition and language., Conclusion: This study demonstrates that in NCH aging individuals, MPS are associated with cortical and subcortical vascular and atrophic changes, and are probably, a warning sign of incipient cognitive decline. Subjects with MPS should manage rigorously cerebral SVD to prevent future physical and cognitive disabilities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Adolescence is associated with enhanced striatal activity in response to rewards. This has been linked to increased risk-taking behavior and negative health outcomes. However, striatal activity is also important for learning, yet it is unknown whether heightened striatal responses in adolescence also benefit cognitive learning performance. In this longitudinal fMRI study (736 scans spanning 5 years in participants ages 8-29), we investigate whether adolescents show enhanced striatal activity during feedback learning, and whether this enhanced activity is associated with better learning performance. Here we report that neural activity indicating sensitivity to informative value of feedback peaks in late adolescence and occurs in dorsal caudate, ventral caudate, and nucleus accumbens. Increased activity in dorsal and ventral caudate predicts better current and future learning performance. This suggests that enhanced striatal activity in adolescents is adaptive for learning and may point to adolescence as a unique life phase for increased feedback-learning performance.

Purpose: Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to investigate sub-cortical morphological alterations in RE children with left, right, or bilateral hemispheric focus and its association with cognition., Methods: Participants include 41 children with rolandic epilepsy and 38 healthy controls (age 8-14 years), recruited from CHU Sainte-Justine Montreal Children Hospital (N=40) and Basel's Children Hospital (N=39). Quantitative volumetric assessment of putamen and caudate structures was performed on T1-weighted MR scans along with the morphological analysis to test for differences between patients and controls. These analyses were performed considering the side of epilepsy focus in all participants. Correlations were investigated between the sub-cortical morphometry and cognitive indices such as intelligence quotient (IQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI)., Results: Children with bilateral BECTS showed statistically significant volume reduction in right caudate (p<.05), while no statistically significant putamen volumetric changes were detected in BECTS participants compared to normal controls. According to a spectral-based groupwise shape analysis, regional alterations were found in both putamen and caudate structures of children with BECTS. In particular, children with left BECTS showed significant outward local deformity in left putamen and individuals with bilateral BECTS showed inward local group differences in both right putamen and right caudate. The correlation assessment showed positive association between the volume of the left caudate and cognitive indices in the group containing all BECTS participants. Negative correlation was found between putamen sub-regional shape alterations and cognition in individuals with right BECTS and in all BECTS participants. Negative associations between caudate sub-regional morphologies and cognitive indices were detected in left cohort., Significance: We have confirmed putamen and caudate shape alterations in children with BECTS. However, our results further suggest that variations in sub-cortical shape affect cognitive functions. Importantly, we have demonstrated that shape alterations and their relation with cognition depend on the side of epilepsy focus. Our results point to different syndromic entities in the BECTS population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain., Methods: Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex)., Results: Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies., Conclusions: Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

Poor response inhibition is a hallmark of pediatric traumatic brain injury (TBI). We assessed motor response inhibition by measuring commission error rates on Simple (minimized cognitive demands) and Motivation (monetary reward) Go/No-Go tasks, comparing 17 children with chronic TBI (>1 year post-injury) and 14 matched, uninjured peers. Using resting state functional magnetic resonance imaging (fMRI), we examined between-group differences in whole-brain intrinsic connectivity of the motor network as derived from the averaged time course of bilateral primary motor cortex seeds, to identify regions of interest (ROIs) for brain-behavior correlations. Independent sample t tests compared Go/No-Go performance and connectivity at the ROI level. Pearson correlations examined relationships between intrinsic connectivity at the ROI level and Go/No-Go performance. Adolescents with TBI showed poorer performance on Simple and Motivation Go/No-Go tasks compared with controls. In whole-brain contrasts, adolescents with TBI showed significantly reduced functional connectivity between the motor network and voxels within the left caudate. Furthermore, in ROI analyses, the group with TBI had significantly lower connectivity between the motor network and left caudate and numerically lower connectivity between the motor network and right caudate. In adolescents with TBI, lower motor network to left caudate connectivity correlated with poorer Simple task performance; lower motor network to right caudate connectivity correlated with poorer Simple and Motivation task performance. No significant brain-behavior relationships existed among controls. These results are consistent with previous pediatric TBI literature and suggest that disrupted intrinsic connectivity of a corticostriatal motor network may contribute to response inhibition deficits.

Competing Interests: Competing interests: None declared.

Background: Females are more likely than males to develop major depressive disorder (MDD). The current study used fMRI to compare the neural correlates of autobiographical memory (AM) recall between males and females diagnosed with MDD. AM overgenerality is a persistent cognitive deficit in MDD, the magnitude of which is correlated with depressive severity only in females. Delineating the neurobiological correlates of this deficit may elucidate the nature of sex-differences in the diathesis for developing MDD., Methods: Participants included unmedicated males and females diagnosed with MDD (n = 20/group), and an age and sex matched healthy control group. AM recall in response to positive, negative, and neutral cue words was compared with a semantic memory task., Results: The behavioral properties of AMs did not differ between MDD males and females. In contrast, main effects of sex on cerebral hemodynamic activity were observed in left dorsolateral prefrontal cortex and parahippocampal gyrus during recall of positive specific memories, and middle prefrontal cortex (mPFC), and precuneus during recall of negative specific memories. Moreover, main effects of diagnosis on regional hemodynamic activity were observed in left ventrolateral prefrontal cortex and mPFC during positive specific memory recall, and dorsal anterior cingulate cortex during negative specific memory recall. Sex × diagnosis interactions were evident in the dorsomedial prefrontal cortex, caudate, and precuneus during positive memory recall, and in the posterior cingulate cortex, insula, precuneus and thalamus during negative specific memory recall., Conclusions: The differential hemodynamic changes conceivably may reflect sex-specific cognitive strategies during recall of AMs irrespective of the phenomenological properties of those memories.

Objective: Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties., Methods: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions., Results: Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05)., Conclusions: These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status., (Copyright © 2017. Published by Elsevier Inc.)

Background: Few neuroimaging studies compare individuals affected with bipolar disorder (BP), at high familial risk of BP, and at low risk to identify endophenotypes for BP. None have examined variability in attention, despite promising behavioral work in this area. We used functional magnetic resonance imaging (fMRI) methods uniquely powered to compare the neural correlates of attention variability in these three groups., Methods: The present study examined 8- to 25-year-old individuals (n = 106) who completed an fMRI attention task: 24 with BP, 29 at risk based on a first-degree relative with BP, and 53 healthy, low-risk individuals. Group differences in intrasubject variability in reaction time were examined, and a sophisticated fMRI analytic approach was used to quantify precisely trialwise associations between reaction time and brain activity. The latter has not been examined previously in BP or risk of BP., Results: Relative to healthy individuals, those with BP or at risk for BP exhibited increased reaction time variability (F 2,102 = 4.26, p = .02, η p 2 = .08). Importantly, we identified blunted relationships between trialwise variation in reaction time and brain activity in the inferior and middle frontal gyri, precuneus, cingulate cortex, caudate, and postcentral gyrus (all regions: p < .001, η p 2 > .06) in both at-risk and BP individuals compared with healthy, low-risk individuals. This blunting partially mediated group differences in reaction time variability (β = .010, 95% confidence interval 0.002 to 0.020, Sobel Z = 2.08, p = .038)., Conclusions: Blunting in key frontal, cingulate, and striatal areas was evident in unaffected, at-risk individuals and in euthymic BP patients. Elucidating such novel neural endophenotypes can facilitate new approaches to BP prediction, diagnosis, and prevention., (Published by Elsevier Inc.)

Objectives: The purpose of this study was to inform the design of randomized clinical trials in early-stage manifest Huntington's disease through analysis of longitudinal data from TRACK-Huntington's Disease (TRACK-HD), a multicenter observational study., Methods: We compute sample sizes required for trials with candidate clinical, functional, and imaging outcomes, whose aims are to reduce rates of change. The calculations use a 2-stage approach: first using linear mixed models to estimate mean rates of change and components of variability from TRACK-HD data and second using these to predict sample sizes for a range of trial designs., Results: For each outcome, the primary drivers of the required sample size were the anticipated treatment effect and the duration of treatment. Extending durations from 1 to 2 years yielded large sample size reductions. Including interim visits and incorporating stratified randomization on predictors of outcome together with covariate adjustment gave more modest, but nontrivial, benefits. Caudate atrophy, expressed as a percentage of its baseline, was the outcome that gave smallest required sample sizes., Discussion: Here we consider potential required sample sizes for clinical trials estimated from naturalistic observation of longitudinal change. Choice among outcome measures for a trial must additionally consider their relevance to patients and the expected effect of the treatment under study. For all outcomes considered, our results provide compelling arguments for 2-year trials, and we also demonstrate the benefits of incorporating stratified randomization coupled with covariate adjustment, particularly for trials with caudate atrophy as the primary outcome. The benefits of enrichment are more debatable, with statistical benefits offset by potential recruitment difficulties and reduced generalizability. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

To assess how tobacco smoking status affects baseline dopamine D2/D3 (D2R) receptor availability and methylphenidate-induced dopamine (DA) release, we retrospectively analyzed D2R availability measures of 8 current smokers, 10 ex-smokers, and 18 nonsmokers who were scanned with positron emission tomography and [ 11 C]raclopride, after administration of an injection of placebo or 0.5 mg/kg i.v. methylphenidate. There was a significant effect of smoking status on baseline striatal D2R availability; with current smokers showing lower striatal D2R availability compared with nonsmokers (caudate, putamen, and ventral striatum) and with ex-smokers (caudate and putamen). Baseline striatal D2R did not differ between nonsmokers and ex-smokers. The effect of smoking status on methylphenidate-induced DA release tended to be lower in smokers but the difference was not significant (p=0.08). For behavioral measures, current smokers showed significantly higher aggression scores compared with both nonsmokers and ex-smokers. These results suggest that with abstinence ex-smokers may recover from low striatal D2R availability and from increased behavioral aggression seen in active smokers. However, longitudinal studies are needed to assess this within abstaining smokers.

Aim: Continence is dependent on anorectal-brain interactions. Consequently, aberrations of the brain-gut axis may be important in the pathophysiology of faecal incontinence (FI) in certain patients. The aim of this study was to assess the feasibility of recording brain responses to rectal mechanical stimulation in patients with FI using functional magnetic resonance imaging (fMRI)., Method: A prospective, cohort pilot study was performed to assess brain responses during rectal stimulation in 14 patients [four men, mean (SD) age 62 (15) years]. Blood oxygen level dependent (BOLD) signals were measured by fMRI during rest and mechanical distension, involving random repetitions of isobaric phasic rectal distensions at fixed (15 and 45 mmHg) and variable (10% above sensory perception threshold) pressures., Results: Increases in BOLD signals in response to high pressure rectal distension (45 mmHg) and maximum toleration were observed in the cingulate gyrus, thalamus, insular cortex, inferior frontal gyrus, cerebellum, caudate nucleus, supramarginal gyrus, putamen and amygdala. Additionally, activation of the supplementary motor cortex and caudate nucleus with inconsistent activity in the frontal lobe was observed., Conclusions: This study has demonstrated the feasibility of recording brain responses to rectal mechanical stimulation using fMRI in patients with FI, revealing activity in widespread areas of the brain involved in visceral sensory processing. The observed activity in the supplementary motor cortex and caudate nucleus, with relative paucity of activity in the frontal lobes, warrants investigation in future studies to determine whether aberrations in cerebral processing of rectal stimuli play a role in the pathogenesis of FI., (Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.)

In patients with premotor Huntington's disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13.2 years) and 11 age- and sex-matched controls (5 males; 46.2 ± 11.9 years, p > 0.3). On 3-T T1-weighted images, bilateral caudate volumes were manually delineated. The resulting labels were converted to a surface, triangulated with 1002 points equally distributed across subjects using SPHARM-PDM. Displacement vectors were then computed between each individual and a template surface representing the whole cohort. Computing point-wise Jacobian determinants (JD) from these vectors quantified local volumes. We found decreases in bilateral global caudate volumes in the pmHD group compared to controls (t = 3.4; p = 0.002). Point-wise analysis of local volumes mapped caudate atrophy in pmHD primarily onto medial surface (t > 2.7; FDR < 0.05), with most pronounced changes in anteromedial subdivision. In a combined group of patients and controls, volume within the area presenting significant group difference was positively correlated with scores of executive function (r = 0.7; p < 0.001) and working memory (r = 0.6; p = 0.002). In patients, the caudate atrophy was associated with increase in disease burden (r = 0.7; p = 0.005). Caudate subnuclear atrophy measured using our surface-based morphometric technique is evident in pmHD, correlates with clinical variables, and may provide a more sensitive biomarker than global volumes.

Background: Findings from longitudinal follow-up studies in patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) have shown that most patients will eventually develop the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Neuroinflammation in the form of microglial activation is present in synucleinopathies and is a potential therapeutic target to halt or delay the neurodegenerative process. We aimed to investigate whether neuroinflammation is present in patients with IRBD and its possible relation to nigrostriatal dopamine function., Methods: In this prospective, case-control, PET study, patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment were recruited from tertiary sleep centres in Spain (Barcelona) and Denmark (Aarhus). We included patients with polysomnography-confirmed IRBD according to established criteria. Healthy controls were recruited through newspaper advertisements. Controls had no motor or cognitive complaints, a normal neurological examination, and a mean group age similar to the IRBD group. In patients with IRBD, we assessed microglial activation in the substantia nigra, putamen, and caudate with 11 C-PK11195 PET, and dopaminergic axon terminal function in the putamen and caudate with 18 F-DOPA PET. Controls underwent either 11 C-PK11195 PET or 18 F-DOPA PET. We compared 18 F-DOPA uptake and 11 C-PK11195 binding potential between groups with an unpaired, two-tailed Student's t test., Findings: Between March 23, 2015, and Oct 19, 2016, we recruited 20 consecutive patients with IRBD and 19 healthy controls. 11 C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD compared with controls (Student's t test, mean difference 0·153 [95% CI 0·055 to 0·250], p=0·003), but not on the right side (0·121 [-0·007 to 0·250], p=0·064). 11 C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. 18 F-DOPA uptake was reduced in IRBD in the left putamen (-0·0032 [-0·0044 to -0·0021], p<0·0001) and right putamen (-0·0032 [-0·0044 to -0·0020], p<0·0001), but not in the caudate., Interpretation: In patients with IRBD, increased microglial activation was detected by PET in the substantia nigra along with reduced dopaminergic function in the putamen. Further studies, including more participants than were in this study and longitudinal follow-up, are needed to support our findings and evaluate whether the presence of activated microglia in patients with IRBD represents a marker of short-term conversion to a clinically defined synucleinopathy in the near future., Funding: Danish Council for Independent Research, Instituto de Salud Carlos III (Spain)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share abnormalities in hot executive functions such as reward-based decision-making, as measured in the temporal discounting task (TD). No studies, however, have directly compared these disorders to investigate common/distinct neural profiles underlying such abnormalities. We wanted to test whether reward-based decision-making is a shared transdiagnostic feature of both disorders with similar neurofunctional substrates or whether it is a shared phenotype with disorder-differential neurofunctional underpinnings., Methods: Age and IQ-matched boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain activation and performance were compared between groups., Results: Boys with ASD showed greater choice-impulsivity than OCD and control boys. Whole-brain between-group comparison revealed shared reductions in ASD and OCD relative to control boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal cortex extending into medial/inferior prefrontal cortex, and in cerebellum, posterior cingulate and precuneus. For immediate-delayed choices, patients relative to controls showed reduced activation in anterior cingulate/ventromedial prefrontal cortex reaching into left caudate, which, at a trend level, was more decreased in ASD than OCD patients, and in bilateral temporal and inferior parietal regions., Conclusions: This first fMRI comparison between youth with ASD and with OCD, using a reward-based decision-making task, shows predominantly shared neurofunctional abnormalities during TD in key ventromedial, orbital- and inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal foresight and reward processing, suggesting trans-diagnostic neurofunctional deficits.

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

The Patlak graphical analysis (PGA REF ) for quantification of irreversible tracer binding with a reference tissue model was approximated by a dual time point imaging approach (DTP REF ). The DTP REF was applied to 18 [ 18 F]-FDOPA brain scans using the occipital cortex as reference region (DTP OCC ) and compared to both PGA OCC and striatal-to-occipital ratios (SOR). Pearson correlation analysis and Bland-Altman plots showed an excellent correlation and good agreement between DTP OCC and PGA OCC , while correlations between SOR and PGA OCC were consistently lower. Linear discriminant analysis (LDA) demonstrated a similar performance for all methods in differentiating patients with Parkinson's disease (PD) from healthy controls (HC). Specifically for [ 18 F]-FDOPA brain imaging, these findings validate DTP OCC as an approximation for PGA OCC , providing the same quantitative information while reducing the acquisition time to two short static scans. For PD patients, this approach can greatly improve patient comfort while reducing motion artifacts and increasing image quality. In general, DTP REF can improve the clinical applicability of tracers with irreversible binding characteristics when a reference tissue is available.

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)