A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward‐driven behavior. Although reward‐driven behavior is supported by subcortical‐medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting‐state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three‐wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self‐reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age‐related strengthening of subcortico‐subcortical and cortico‐cortical connectivity. Subcortical–cortical connectivity, such as, between the nucleus accumbens—frontal medial cortex, and the caudate—dorsal anterior cingulate cortex, however, weakened across age. Model‐based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical–cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.     

Alterations in amplitude of low frequency fluctuation in treatment‐naïve major depressive disorder measured with resting‐state fMRI

There are limited resting‐state functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD). Of these studies, functional connectivity analyses are mostly used. However, a new method based on the magnitude of low frequency fluctuation (LFF) during resting‐state fMRI may provide important insight into MDD. In this study, we examined the amplitude of LFF (ALFF) within the whole brain during resting‐state fMRI in 30 treatment‐naïve MDD subjects and 30 healthy control (HC) subjects. When compared with HC, MDD subjects showed increased ALFF in the frontal cortex (including the bilateral ventral/dorsal anterior cingulate cortex, orbitofrontal cortex, premotor cortex, ventral prefrontal cortex, left dorsal lateral frontal cortex, left superior frontal cortex), basal ganglia (including the right putamen and left caudate nucleus), left insular cortex, right anterior entorhinal cortex and left inferior parietal cortex, together with decreased ALFF in the bilateral occipital cortex, cerebellum hemisphere, and right superior temporal cortex. These findings may relate to characteristics of MDD, such as excessive self‐referential processing and deficits in cognitive control of emotional processing, which may contribute to the persistent and recurrent nature of the disorder. Hum Brain Mapp 35:4979–4988, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Reduced corticostriatal functional connectivity in temporomandibular disorders

Although temporomandibular disorders (TMD) have been associated with abnormal gray matter volumes in cortical areas and in the striatum, the corticostriatal functional connectivity (FC) of patients with TMD has not been studied. Here, we studied 30 patients with TMD and 20 healthy controls that underwent clinical evaluations, including Helkimo indices, pain assessments, and resting‐state functional magnetic resonance imaging scans. The FCs of the striatal regions with the other brain areas were examined with a seed‐based approach. As seeds, we used the dorsal caudate, ventral caudate/nucleus accumbens, dorsal caudal putamen, and ventral rostral putamen regions. Voxel‐wise comparisons with controls revealed that the patients with TMD exhibited reduced FCs in the ventral corticostriatal circuitry, between the ventral striatum and ventral frontal cortices, including the anterior cingulate cortex and anterior insula; in the dorsal corticostriatal circuitry, between the dorsal striatum and the dorsal cortices, including the precentral gyrus and supramarginal gyrus; and also within the striatum. Additionally, we explored correlations between the reduced corticostriatal FCs and clinical measurements. These results directly supported the hypothesis that TMD is associated with reduced FCs in brain corticostriatal networks and that these reduced FCs may underlie the deficits in motor control, pain processing, and cognition in TMD. Our findings may contribute to the understanding of the etiologies and pathologies of TMD.     

Striatal reward areas activated by implicit laughter induced by mimic words in humans: a functional magnetic resonance imaging study

The neurobiological reward components of laughter induced by words were investigated. A functional magnetic resonance imaging-based brain imaging study demonstrated that visualization of mimic words and emotional facial expression words, highly suggestive of laughter, heard by the ear, significantly activate striatal reward centers, including the putamen/caudate/nucleus accumbens, prefrontal cortices, dorsal anterior cingulate cortex and the supplementary motor area, while non-mimic words under the same task that did not imply laughter do not activate these areas in humans. We tested a specific hypothesis that implicit laughter modulates the striatal dopaminergic reward centers by image formation of onomatopoeic words implying laughter and successfully confirmed the hypothesis.     

Oestradiol Modulation of Serotonin Reuptake Transporter and Serotonin Metabolism in the Brain of Monkeys

Serotonin (5-hydroxytryptamine; 5-HT) is an important brain neurotransmitter that is implicated in mental and neurodegenerative diseases and is modulated by ovarian hormones. Nevertheless, the effect of oestrogens on 5-HT neurotransmission in the primate caudate nucleus, putamen and nucleus accumbens, which are major components of the basal ganglia, and the anterior cerebral cortex, mainly the frontal and cingulate gyrus, is not well documented. The present study evaluated 5-HT reuptake transporter (SERT) and 5-HT metabolism in these brain regions in response to 1-month treatment with 17β-oestradiol in short-term (1 month) ovariectomised (OVX) monkeys (Macaca fascicularis). SERT-specific binding was measured by autoradiography using the radioligand [³H]citalopram. Biogenic amine concentrations were quantified by high-performance liquid chromatography. 17β-Oestradiol increased SERT in the superior frontal cortex and in the anterior cingulate cortex, in the nucleus accumbens, and in subregions of the caudate nucleus of OVX monkeys. 17β-Oestradiol left [³H]citalopram-specific binding unchanged in the putamen, as well as the dorsal and medial raphe nucleus. 17β-Oestradiol treatment decreased striatal concentrations of the precursor of 5-HT, 5-hydroxytryptophan, and increased 5-HT, dopamine and 3-methoxytyramine concentrations in the nucleus accumbens, caudate nucleus and putamen, whereas the concentrations of the metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid remained unchanged. No effect of 17β-oestradiol treatment was observed for biogenic amine concentrations in the cortical regions. A significant positive correlation was observed between [³H]citalopram-specific binding and 5-HT concentrations in the caudate nucleus, putamen and nucleus accumbens, suggesting their link. These results have translational value for women with low oestrogen, such as those in surgical menopause or perimenopause.     

Imbalance in subregional connectivity of the right temporoparietal junction in major depression

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive‐attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity‐based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting‐state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well‐matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta‐data from a large‐scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931–2942, 2016. © 2016 Wiley Periodicals, Inc .     

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.Key words: ARMS, fMRI, resting state, striatum     

The implication of frontostriatal circuits in young smokers: A resting‐state study

The critical roles of frontostriatal circuits had been revealed in addiction. With regard to young smokers, the implication of frontostriatal circuits resting‐state functional connectivity (RSFC) in smoking behaviors and cognitive control deficits remains unclear. In this study, the volume of striatum subsets, i.e., caudate, putamen, and nucleus accumbens, and corresponding RSFC differences were investigated between young smokers (n₁ = 60) and nonsmokers (n₂ = 60), which were then correlated with cigarette smoking measures, such as pack_years‐cumulative effect of smoking, Fagerström Test for Nicotine Dependence (FTND)‐severity of nicotine addiction, Questionnaire on Smoking Urges (QSU)‐craving state, and Stroop task performances. Additionally, mediation analysis was carried out to test whether the frontostriatal RSFC mediates the relationship between striatum morphometry and cognitive control behaviors in young smokers when applicable. We revealed increased volume of right caudate and reduced RSFC between caudate and dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex in young smokers. Significant positive correlation between right caudate volume and QSU as well as negative correlation between anterior cingulate cortex‐right caudate RSFC and FTND were detected in young smokers. More importantly, DLPFC‐caudate RSFC strength mediated the relationship between caudate volume and incongruent errors during Stroop task in young smokers. Our results demonstrated that young smokers showed abnormal interactions within frontostriatal circuits, which were associated with smoking behaviors and cognitive control impairments. It is hoped that our study focusing on frontostriatal circuits could provide new insights into the neural correlates and potential novel therapeutic targets for treatment of young smokers. Hum Brain Mapp 37:2013–2026, 2016. © 2016 Wiley Periodicals, Inc .     

Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder

Background

Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics.

Methods

Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls.

Results

We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders.

Limitations

Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants.

Conclusion

We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.     

Dopaminergic modulation of resting‐state functional connectivity in de novo patients with Parkinson's disease

Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine‐dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP‐CIT positron emission tomography imaging and resting‐state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine‐dependent functional networks. The major finding is that the patterns of dopamine‐dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine‐dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine‐dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine‐dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine‐dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian‐related motor and cognitive performance. Hum Brain Mapp 35:5431–5441, 2014. © 2014 Wiley Periodicals, Inc .     

Resting state functional connectivity of networks associated with reward and habit in anorexia nervosa

Neurobiological disturbances associated with reward and/or habit learning are theorized to maintain symptoms of anorexia nervosa (AN). Although research has investigated responses in brain regions associated with reward and habit to disorder‐specific cues (e.g., food) and presumed rewards (e.g., money), little is known about the functional organization of the circuits underlying these constructs independent of stimulus. This study aimed to provide initial data on the synchrony of networks associated with reward and habit in AN by comparing resting‐state functional connectivity (RSFC) patterns between AN and healthy control (HC) participants in these circuits and delineating how these patterns relate to symptoms. Using theoretically selected seeds in the nucleus accumbens (NAcc), ventral caudate, and dorsal caudate, reflecting a continuum from reward‐ to habit‐ oriented regions, RSFC patterns were compared between AN restricting subtype (n = 19) and HC (n = 19) participants (cluster threshold: p < .01). Exploratory correlations between RSFC z‐scores and Eating Disorder Examination (EDE) scores, BMI, and illness duration were conducted. The AN group demonstrated lower RSFC between the NAcc and superior frontal gyrus, between the ventral caudate and frontal and posterior regions, and between the dorsal caudate and frontal, temporal, and posterior regions. In the AN group, lower NAcc‐ superior frontal gyrus RSFC correlated with greater EDE Global scores (r = ?.58, CI: ?.83, ?.13). These resting‐state synchrony disruptions of the ventral and dorsal frontostriatal circuits, considered in context of the broader literature, support the utility of further investigating possible reward and habit disturbances supporting symptoms in AN.     

Altered frontostriatal coupling in pre‐manifest Huntington’s disease: effects of increasing cognitive load

Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre‐symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre‐HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre‐HD individuals. Methods: Sixteen healthy controls and sixteen pre‐HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load‐dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre‐HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre‐HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre‐HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre‐HD individuals are modulated by cognitive demand.     

Behavioral sensitization to binge-pattern cocaine administration is not associated with changes in protein levels of four major G-proteins

Behavioral sensitization is a characteristic sequelae of repeated cocaine exposure. It likely occurs due to long-lasting neuroadaptations produced by cocaine, although the exact nature of these adaptations has yet to be defined. The goal of the present study was to determine if behavioral sensitization to cocaine is accompanied by alterations in G-protein levels. Adult male rats were administered cocaine or saline three times daily in a binge-pattern for 1, 3, or 14 days and activity monitored. Levels of four major G-protein alpha-subunits, Galphas, Galphaolf, Galphao and Galphai1, and their mRNAs were measured in the nucleus accumbens, caudate putamen, and cingulate/frontal cortex using Western blot analysis and in situ hybridization, respectively. Fourteen days of binge-pattern cocaine administration resulted in behavioral sensitization as evidenced by increased behavioral activity over the 14 days of drug exposure. Results demonstrated that Galphaolf mRNA expression was significantly reduced in the nucleus accumbens after 1, 3 or 14 days of cocaine, whereas Galphai1 mRNA was increased following 3, but not 1 or 14 days of cocaine in the caudate putamen, nucleus accumbens and cingulate cortex. Galphas and Galphao mRNA expression were not altered in any region investigated at any time point. In contrast to gene expression, protein levels of the four G-protein alpha-subunits were not significantly different from saline-injected rats in the caudate putamen, nucleus accumbens, or frontal cortex following 1, 3, or 14 days of cocaine administration. These results suggest that alterations in the level of G-proteins are not necessary for the development of cocaine-induced sensitization.     

Neural substrates of context‐ and person‐dependent altruistic punishment

Human altruistic behaviors are heterogeneous across both contexts and people, whereas the neural signatures underlying the heterogeneity remain to be elucidated. To address this issue, we examined the neural signatures underlying the context‐ and person‐dependent altruistic punishment, conjoining event‐related fMRI with both task‐based and resting‐state functional connectivity (RSFC). Acting as an impartial third party, participants decided how to punish norm violators either alone or in the presence of putative others. We found that the presence of others decreased altruistic punishment due to diffusion of responsibility. Those behavioral effects paralleled altered neural responses in the dorsal anterior cingulate cortex (dACC) and putamen. Further, we identified modulation of responsibility diffusion on task‐based functional connectivity of dACC with the brain regions implicated in reward processing (i.e., posterior cingulate cortex and amygdala/orbital frontal cortex). Finally, the RSFC results revealed that (i) increased intrinsic connectivity strengths of the putamen with temporoparietal junction and dorsolateral PFC were associated with attenuated responsibility diffusion in altruistic punishment and (ii) increased putamen‐dorsomedial PFC connectivity strengths were associated with reduced responsibility diffusion in self‐reported responsibility. Taken together, our findings elucidate the context‐ and person‐dependent altruistic behaviors as well as associated neural substrates and thus provide a potential neurocognitive mechanism of heterogeneous human altruistic behaviors. Hum Brain Mapp 38:5535–5550, 2017. © 2017 Wiley Periodicals, Inc.     

Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder

Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD.     

The lateral and ventromedial prefrontal cortex work as a dynamic integrated system: evidence from FMRI connectivity analysis

Recent functional magnetic resonance imaging (fMRI) investigations of the interaction between cognition and reward processing have found that the lateral prefrontal cortex (PFC) areas are preferentially activated to both increasing cognitive demand and reward level. Conversely, ventromedial PFC (VMPFC) areas show decreased activation to the same conditions, indicating a possible reciprocal relationship between cognitive and emotional processing regions. We report an fMRI study of a rewarded working memory task, in which we further explore how the relationship between reward and cognitive processing is mediated. We not only assess the integrity of reciprocal neural connections between the lateral PFC and VMPFC brain regions in different experimental contexts but also test whether additional cortical and subcortical regions influence this relationship. Psychophysiological interaction analyses were used as a measure of functional connectivity in order to characterize the influence of both cognitive and motivational variables on connectivity between the lateral PFC and the VMPFC. Psychophysiological interactions revealed negative functional connectivity between the lateral PFC and the VMPFC in the context of high memory load, and high memory load in tandem with a highly motivating context, but not in the context of reward alone. Physiophysiological interactions further indicated that the dorsal anterior cingulate and the caudate nucleus modulate this pathway. These findings provide evidence for a dynamic interplay between lateral PFC and VMPFC regions and are consistent with an emotional gating role for the VMPFC during cognitively demanding tasks. Our findings also support neuropsychological theories of mood disorders, which have long emphasized a dysfunctional relationship between emotion/motivational and cognitive processes in depression.     

Mapping adolescent reward anticipation,receipt, and prediction error during the monetary incentive delay task

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward‐related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity.     

Striatal connections of the parietal association cortices in rhesus monkeys

The corticostriatal connections of the parietal association cortices were examined by the autoradiographic technique in rhesus monkeys. The results show that the rostral portion of the superior parietal lobule projects predominantly to the dorsal portion of the putamen, whereas the caudal portion of the superior parietal lobule and the cortex of the upper bank of the intraparietal sulcus have connections with the caudate nucleus as well as with the dorsal portion of the putamen. The medial parietal convexity cortex projects strongly to the caudate nucleus, and has less extensive projections to the putamen. In contrast, the medial parietal cortex within the caudal portion of the cingulate sulcus projects predominantly to the dorsal portion of the putamen, and has only minor connections with the caudate nucleus. The rostral portion of the inferior parietal lobule projects mainly to the ventral sector of the putamen, and has only minor connections with the caudate nucleus. The middle portion of the inferior parietal lobule has sizable projections to both the putamen and the caudate nucleus. The caudal portion of the inferior parietal lobule as well as the lower bank of the intraparietal sulcus project predominantly to the caudate nucleus, and have relatively minor connections with the putamen. The cortex of the parietal opercular region also shows a specific pattern of corticostriatal projections. Whereas the rostral portion projects exclusively to the ventral sector of the putamen, the caudal portion has connections to the caudate nucleus as well. Thus, it seems that parietostriatal projections show a differential topographic distribution; within both the superior and the inferior parietal region, as one progresses from rostral to caudal, there is a corresponding shift in the predominance of projections from the putamen to the caudate nucleus. In addition, with regard to the projections to the putamen, the superior parietal lobule is related mainly to the dorsal portion, and the inferior parietal lobule to the ventral portion. The striatal projections of the cortex of the caudal portion of the cingulate gyrus (corresponding in part to the supplementary sensory area) and of the rostral parietal opercular region (corresponding in part to the second somatosensory area) are directed almost exclusively to the dorsal and ventral sectors of the putamen, respectively. This pattern resembles that of the primary somatosensory cortex. The results are discussed with regard to the overall architectonic organization of the posterior parietal region. Possible functional aspects of parietostriatal connectivity are considered in the light of physiological and behavioral studies. © 1993 Wiley-Liss, Inc.     

Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey

Anterograde tracing methods were used to examine the topographic organization and interrelationship of projections to the neostriatum arising from various areas of association cortex. In contrast to the currently accepted topographic schema, all cortical areas examined project to longitudinal territories that occupy restricted medial-lateral domains of the neostriatum. The posterior parietal and superior arcuate cortices project to dorsolateral portions of the neostriatum; the dorsolateral and dorsomedial frontal cortices project centrally; and the orbitofrontal, anterior cingulate, and superior temporal projections are distributed to ventromedial regions of the caudate nucleus and putamen. In coronal section, cortical terminal fields form a diagonal strip, extending from the dorsal, ventricular border of the caudate nucleus, through the fiber bundles of the internal capsule, to the ventral margin of the putamen. Double labeling studies, in which two cortical areas were injected in the same animal, indicated that convergence of input within neostriatal domains is not governed by reciprocity of corticocortical connectivity. Thus, the interrelationship of projections arising from connectionally linked cortical areas ranged from nearly complete segregation of terminal fields (e.g., from dorsolateral prefrontal and orbital cortices) to extensive overlap of terminal domains (e.g., from frontal and temporal cortices). In the latter case, detailed analysis revealed that frontal and temporal terminals actually were interdigitated rather than intermixed within the zone of overlap. The present findings suggest a new conceptualization of corticostriatal topography in the primate which emphasizes the longitudinal arrangement of cortical terminal domains. Additionally, these findings provide a map for functional parcellation of the neostriatum on the basis of its cortical innervation which may prove useful to understanding normal striatal function, as well as the symptomatology associated with neostriatal injury and disease.     

Olfactory performance and resting state functional connectivity in non‐demented drug naïve patients with Parkinson's disease

Olfactory performance in Parkinson's disease (PD) is closely associated with subsequent cognitive decline. In the present study, we analyzed the olfaction‐dependent functional connectivity with a hypothesis that olfactory performance would influence functional connectivity within key brain areas of PD. A total of 110 nondemented drug‐naïve patients with PD were subdivided into three groups of high score (PD‐H, n = 23), middle score (PD‐M, n = 64), and low score (PD‐L, n = 23) based on olfactory performance. We performed the resting‐state functional connectivity with seed region of interest in the posterior cingulate cortex (PCC) and caudate. An analysis of functional connectivity revealed that PD‐L patients exhibited a significant attenuation of cortical functional connectivity with the PCC in the bilateral primary sensory areas, right frontal areas, and right parietal areas compared to PD‐H or PD‐M patients. Meanwhile, PD‐L patients exhibited a significant enhancement of striatocortical functional connectivity in the bilateral occipital areas and right frontal areas compared to PD‐H or PD‐M patients. In the voxel‐wise correlation analysis, olfactory performance was positively associated with cortical functional connectivity with the PCC in similar areas of attenuated cortical connectivity in PD‐L patients relative to PD‐H patients. On the other hand, the cortical functional connectivity with the caudate was negatively correlated with olfactory performance in similar areas of increased connectivity in PD‐L patients relative to PD‐H patients. The present study demonstrated that resting state functional connectivity exhibits a distinctive pattern depending on olfactory performance, which might shed light on a meaningful relationship between olfactory impairment and cognitive dysfunction in PD. Hum Brain Mapp 36:1716–1727, 2015. © 2014 Wiley Periodicals, Inc.