The functional connectivity of intralaminar thalamic nuclei in the human basal ganglia

Projections of the centromedian‐parafasicularis neurons of the intralaminar thalamus are major inputs of the striatum. Their functional role in the activity of human basal ganglia (BG) is not well known. The aim of this work was to study the functional connectivity of intralaminar thalamic nuclei with other BG by using the correlations of the BOLD signal recorded during “resting” and a motor task. Intralaminar nuclei showed a marked functional connectivity with all the tested BG, which was observed during “resting” and did not change with the motor task. As regards the intralaminar nuclei, BG connectivity was much lower for the medial dorsal nucleus (a thalamic nucleus bordering the intralaminar nuclei) and for the default mode network (although intralaminar nuclei showed a negative correlation with the default mode network). After the “regression” of intralaminar nuclei activity (partial correlation), the functional connectivity of the caudate and putamen nuclei with other BG decreased (but not with the primary sensorimotor cortex). Present data provide evidence that intralaminar nuclei are not only critical for striatal activity but also for the global performance of human BG, an action involving subcortical BG loops more than cortico‐subcortical loops. The high correlation found between BG suggest that, similarly to that reported in other brain centers, the very‐slow frequency fluctuations are relevant for the functional activity of these centers. Hum Brain Mapp 36:1335–1347, 2015. © 2014 Wiley Periodicals, Inc .     

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high‐resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus‐response learning (Experiment 2). In the first experiment, we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment, we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments, the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well‐learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. © 2015 Wiley Periodicals, Inc.     

Functional connectivity‐based identification of subdivisions of the basal ganglia and thalamus using multilevel independent component analysis of resting state fMRI

This study aimed to identify subunits of the basal ganglia and thalamus and to investigate the functional connectivity among these anatomically segregated subdivisions and the cerebral cortex in healthy subjects. For this purpose, we introduced multilevel independent component analysis (ICA) of the resting‐state functional magnetic resonance imaging (fMRI). After applying ICA to the whole brain gray matter, we applied second‐level ICA restrictively to the basal ganglia and the thalamus area to identify discrete functional subunits of those regions. As a result, the basal ganglia and the thalamus were parcelled into 31 functional subdivisions according to their temporal activity patterns. The extracted parcels showed functional network connectivity between hemispheres, between subdivisions of the basal ganglia and thalamus, and between the extracted subdivisions and cerebral functional components. Grossly, these findings correspond to cortico‐striato‐thalamo‐cortical circuits in the brain. This study also showed the utility of multilevel ICA of resting state fMRI in brain network research. Hum Brain Mapp, 2013. © 2012 Wiley Perodicals, Inc.     

Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum

In order to determine what types of neurons in the striatum receive direct synaptic input from corticostriatal and thalamostriatal fibres and whether these afferents converge on individual striatal neurons, double anterograde labelling of axon terminals was combined with Golgi impregnation at both the light and electron microscopic levels. The area of the central neostriatum that receives input from both the parafascicular nucleus of the thalamus and the somatosensory cortex was identified by retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA). The same region of the neostriatum was studied in rats that had received multiple electrolytic lesions in the somatosensory cortex and also an injection of HRP-WGA in different parts of the parafascicular nucleus. Sections of this part of the neostriatum were impregnated by the single-section Golgi procedure after revealing anterogradely transported HRP-WGA. Twelve Golgi-impregnated spiny neurons were recovered and examined in the light and electron microscope after gold-toning. Ten of these neurons were typical very densely spiny medium-size neurons and they were all found to receive asymmetric synaptic input on dendritic spines from degenerating corticostriatal boutons. However, even though numerous boutons labelled anterogradely by HRP-WGA from the parafascicular nucleus were found within the dendritic fields of neurons that received cortical input, none of the terminals from the thalamus made synaptic contact with these neurons. Instead, all 96 thalamostriatal boutons studied were found in asymmetric synaptic contact with dendritic shafts of other neurons. Two such neurons that received input from the parafascicular nucleus were Golgi-impregnated and appeared to be medium-size spiny neurons, but they had a lower density of spines than the typical very densely spiny neurons. An independent confirmation that the targets of thalamostriatal neurons originating in the parafascicular nucleus are dendritic shafts was provided by studying the boutons labelled following electrolytic lesioning or injection of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into this nucleus: these boutons were also found to form asymmetric synaptic contacts with dendritic shafts within the neostriatum. It is concluded that although afferents from the somatosensory cortex and from the parafascicular nucleus converge upon the same part of the neostriatum, they probably do not converge upon the same spiny neurons. The afferents from the neocortex form synapses on the spines of densely spiny medium-size neurons, whereas terminals originating from neurons in the parafascicular nucleus are in synaptic contact with the dendritic shafts of what appears to be a morphologically distinct type of medium-size spiny neuron. The integration of the inputs from these two areas probably involves the local axon collaterals of these two types of spiny neuron.     

Functional connectivity during orthographic,phonological, and semantic processing of Chinese characters identifies distinct visuospatial and phonosemantic networks

While neuroimaging studies have identified brain regions associated with single word reading, its three constituents, namely, orthography, phonology, and meaning, and the functional connectivity of their networks remain underexplored. This study examined the neurocognitive underpinnings of these neural activations and functional connectivity of the identified brain regions using a within‐subject design. Thirty‐one native Mandarin speakers performed orthographic, phonological, and semantic judgment tasks during functional magnetic resonance imaging. The results indicated that the three processes shared a core network consisting of a large region in the left prefrontal cortex, fusiform gyrus, and medial superior frontal gyrus but not the superior temporal gyrus. Orthographic processing more strongly recruited the left dorsolateral prefrontal cortex, left superior parietal lobule and bilateral fusiform gyri; semantic processing more strongly recruited the left inferior frontal gyrus and left middle temporal gyrus, whereas phonological processing more strongly activated the dorsal part of the precentral gyrus. Functional connectivity analysis identified a posterior visuospatial network and a frontal phonosemantic network interfaced by the left middle frontal gyrus. We conclude that reading Chinese recruits cognitive resources that correspond to basic task demands with unique features best explained in connection with the individual reading subprocesses.     

Communication with emblematic gestures: shared and distinct neural correlates of expression and reception

Emblematic (or symbolic) gestures allow individuals to convey a variety of thoughts and emotions ranging from approval to hostility. The use of such gestures involves the execution of a codified motor act by the addresser and its perception and decoding by the addressee. To examine underlying common and distinct neural correlates, we used fMRI tasks in which subjects viewed video clips of emblematic one-hand gestures. They were asked to (1) take the perspective of the addresser and imagine executing the gestures ("expression" condition), and to (2) take the perspective of the addressee and imagine being confronted with the gestures ("reception" condition). Common areas of activation were found in inferior frontal, medial frontal, and posterior temporal cortices with left-hemispheric predominance as well as in the cerebellum. The distinction between regions specifically involved in the expression or reception condition partly resembled the dorsal and ventral stream dichotomy of visual processing with junctions in inferior frontal and medial prefrontal cortices. Imagery of gesture expression involved the dorsal visual stream as well as higher-order motor areas. In contrast, gesture reception encompassed regions related to semantic processing, and medial prefrontal areas known to be involved in the process of understanding the intentions of others. In conclusion, our results provide evidence for a dissociation in representations of emblematic gesture processing between addresser and addressee in addition to shared components in language-related areas.     

The glutamate-enriched cortical and thalamic input to neurons in the subthalamic nucleus of the rat: Convergence with GABA-positive terminals

Neurons of the subthalamic nucleus play a key role in the normal physiology and the pathophysiology of the basal ganglia. In order to understand better how the activity of subthalamic neurons and hence the output of the basal ganglia are controlled, we have reexamined the topography and examined in detail the synaptology and neurochemical nature of the two major excitatory projections to the subthalamic nucleus, that from the cortex and from the parafascicular nucleus of the thalamus. The approach was to use anterograde neuronal tracing and postembedding immunocytochemistry for amino acid transmitters. In confirmation of previous findings the cortical and thalamic projections were topographically organized, although the topography was more finely organized, and the projections more extensive, than previously demonstrated. Cortical and thalamic terminals made asymmetrical synaptic contacts with the dendrites and spines of subthalamic neurons. The thalamic terminals contacted larger postsynaptic targets, and therefore presumably more proximal regions of subthalamic neurons, than did the cortical terminals. Quantitative analysis of the postembedding immunolabelled sections revealed that the cortical and thalamic terminals were significantly enriched in glutamate-immunoreactivity when compared to identified γ-aminobutyric acid (GABA)-positive terminals, supporting physiological studies that suggest that these projections use glutamate as their neurotransmitter. In addition a small population of nonanterogradely labelled terminals that formed asymmetrical synapses and were immunopositive for GABA were identified. A larger population of terminals that formed symmetrical synapses were also immunbpositive for GABA and were probably derived from the globus pallidus. The latter type of terminal was found to make convergent synaptic input with cortical or thalamic terminals on this dendrites and spines of subthalamic neurons, indicating that the “indirect pathways” by which information flows through the basal ganglia converge at the level of individual neurons in the subthalamic nucleus. © 1995 Wiley-Liss, Inc.     

Two mechanisms of protracted reaction times mediated by dissociable cortical networks

When people divide attention between two sensory modalities and respond rapidly to stimuli in either modality, the reaction times (RTs) are longer than when they selectively attend and respond to one sensory modality. There is a further increase in RT when subjects use different fingers to respond to stimuli from different modalities as compared to when they use the same finger for both modalities. Here we use functional magnetic resonance imaging to show that division of attention bilaterally activates the caudal prefrontal areas near the precentral sulcus and areas in the intraparietal sulcus. All RT tasks, whether different fingers for different modalities or one finger for both modalities was used, activated identical motor areas 4a, 4p, supplementary and cingulate, the basal ganglia and the ventral anterior thalami. The increased blood oxygen level-dependent signal from motor cortical areas was anatomically distinct from the prefrontal/parietal areas. These anatomically dissociable neural substrates of division of attention and motor control may be responsible for the different types of RT delays that we have found. In the brain, there were no differences in the BOLD signal irrespective of whether the effector was specified a priori or was specified only after the sensory signal was received.     

Functional alterations of large-scale brain networks related to cognitive control in obsessive-compulsive disorder

Objectives: Neuroimaging studies have consistently implicated alterations of the basal ganglia and orbitofrontal cortex in the pathophysiology of OCD, however, recent work also emphasizes more diffuse patterns of brain alteration as occurring in this disorder. The goal of this study was to extend such observations by investigating large‐scale brain functional network correlates of cognitive‐control performance in OCD patients. Experimental design: We combined fMRI with a validated task of cognitive control and a multivariate statistical method to assess multiple functional networks encompassing broad task‐relevant cortical regions in OCD patients and matched controls. Functional networks of interest were targeted a priori and the groups were compared in terms of the spatiotemporal profile of network responses (functional connectivity) during the task performance in a data‐driven manner. Principal observations: Task performance was equivalent in both groups and each distinct network demonstrated strong overlap in its general response during task. However, significant differences in functional connectivity were also observed between groups that appeared driven by specific phases of task performance. Such differences were most pronounced during rest‐task transitions and mainly involved dorsal anterior cingulate and insular cortices within the paralimbic network. Relative heightened functional connectivity of insula in patients during task correlated with a measure of patients' state anxiety. Conclusions: Our findings provide a novel functional imaging characterization of brain network alterations associated with cognitive‐control in OCD. Additionally, these findings raise questions about the role of patients' arousal states on the performance of cognitive imaging tasks that are otherwise assumed to be emotionally neutral. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.     

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.     

Primary and secondary neural networks of auditory prepulse inhibition: a functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response

Feedforward inhibition deficits have been consistently demonstrated in a range of neuropsychiatric conditions using prepulse inhibition (PPI) of the acoustic startle eye-blink reflex when assessing sensorimotor gating. While PPI can be recorded in acutely decerebrated rats, behavioural, pharmacological and psychophysiological studies suggest the involvement of a complex neural network extending from brainstem nuclei to higher order cortical areas. The current functional magnetic resonance imaging study investigated the neural network underlying PPI and its association with electromyographically (EMG) recorded PPI of the acoustic startle eye-blink reflex in 16 healthy volunteers. A sparse imaging design was employed to model signal changes in blood oxygenation level-dependent (BOLD) responses to acoustic startle probes that were preceded by a prepulse at 120 ms or 480 ms stimulus onset asynchrony or without prepulse. Sensorimotor gating was EMG confirmed for the 120-ms prepulse condition, while startle responses in the 480-ms prepulse condition did not differ from startle alone. Multiple regression analysis of BOLD contrasts identified activation in pons, thalamus, caudate nuclei, left angular gyrus and bilaterally in anterior cingulate, associated with EMG-recorded sensorimotor gating. Planned contrasts confirmed increased pons activation for startle alone vs 120-ms prepulse condition, while increased anterior superior frontal gyrus activation was confirmed for the reverse contrast. Our findings are consistent with a primary pontine circuitry of sensorimotor gating that interconnects with inferior parietal, superior temporal, frontal and prefrontal cortices via thalamus and striatum. PPI processes in the prefrontal, frontal and superior temporal cortex were functionally distinct from sensorimotor gating.     

The transition from vision to language: Distinct patterns of functional connectivity for subregions of the visual word form area

Reading entails transforming visual symbols to sound and meaning. This process depends on specialized circuitry in the visual cortex, the visual word form area (VWFA). Recent findings suggest that this text-selective cortex comprises at least two distinct subregions: the more posterior VWFA-1 is sensitive to visual features, while the more anterior VWFA-2 processes higher level language information. Here, we explore whether these two subregions also exhibit different patterns of functional connectivity. To this end, we capitalize on two complementary datasets: Using the Natural Scenes Dataset (NSD), we identify text-selective responses in high-quality 7T adult data (N = 8), and investigate functional connectivity patterns of VWFA-1 and VWFA-2 at the individual level. We then turn to the Healthy Brain Network (HBN) database to assess whether these patterns replicate in a large developmental sample (N = 224; age 6–20 years), and whether they relate to reading development. In both datasets, we find that VWFA-1 is primarily correlated with bilateral visual regions. In contrast, VWFA-2 is more strongly correlated with language regions in the frontal and lateral parietal lobes, particularly the bilateral inferior frontal gyrus. Critically, these patterns do not generalize to adjacent face-selective regions, suggesting a specific relationship between VWFA-2 and the frontal language network. No correlations were observed between functional connectivity and reading ability. Together, our findings support the distinction between subregions of the VWFA, and suggest that functional connectivity patterns in the ventral temporal cortex are consistent over a wide range of reading skills.     

Pramipexole modulates the neural network of reward anticipation

Pramipexole is widely prescribed to treat Parkinson's disease. It has been found to cause impulse control disorders such as pathological gambling. To examine how pramipexole modulates the network of reward anticipation, we carried out a pharmacological functional magnetic resonance imaging study with a double-blind, within-subject design. During the anticipation of monetary rewards, pramipexole increased the activity of the nucleus accumbens (NAcc), enhanced the interaction between the NAcc and the anterior insula, but weakened the interaction between the NAcc and the prefrontal cortex. These results suggest that pramipexole may exaggerate incentive and affective responses to possible rewards, but reduce the top-down control of impulses, leading to an increase in impulsive behaviors. This imbalance between the prefrontal-striatum connectivity and the insula-striatum connectivity may represent the neural mechanism of pathological gambling caused by pramipexole.     

Step‐by‐step: The effects of physical practice on the neural correlates of locomotion imagery revealed by fMRI

Previous studies have shown that mental imagery is a suitable tool to study the progression of the effect of practice on brain activation. Nevertheless, there is still poor knowledge of changes in brain activation patterns during the very early stages of physical practice. In this study, early and late practice stages of different kinds of locomotion (i.e., balanced and unbalanced) have been investigated using functional magnetic resonance imaging during mental imagery of locomotion and stance. During the task, cardiac activity was also recorded. The cerebral network comprising supplementary motor area, basal ganglia, bilateral thalamus, and right cerebellum showed a stronger activation during the imagery of locomotion with respect to imagery of stance. The heart beat showed a significant increase in frequency during the imagery of locomotion with respect to the imagery of stance. Moreover, early stages of practice determined an increased activation in basal ganglia and thalamus with respect to late stages. In this way, it is proposed the modulation of the brain network involved in the imagery of locomotion as a function of physical practice time. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Cortical and thalamic projections to cytoarchitectural areas 6Va and 8C of the marmoset monkey: Connectionally distinct subdivisions of the lateral premotor cortex

We studied the afferent connections of two cytoarchitectural subdivisions of the caudolateral frontal cortex, areas 6Va and 8C, in marmoset monkeys. These areas received connections from the same set of thalamic nuclei, including main inputs from the ventral lateral and ventral anterior complexes, but differed in their patterns of corticocortical connections. Areas 8C and 6Va had reciprocal interconnections, and received similar proportions of afferents from premotor areas 6M and 6DC, and from the prefrontal cortex. However, area 8C received stronger inputs from frontal areas that have been implicated in oculomotor functions, whereas area 6Va received stronger projections from the primary motor area. Somatosensory projections to area 6Va were generally stronger than those to area 8C, and originated from several areas; in contrast, only the second somatosensory area (S2) sent major inputs to area 8C. Finally, although both 6Va and 8C received major inputs from the rostral posterior parietal cortex (putative homologs of areas PE, PF, and PFG), area 8C also received a variety of smaller connections from posterior midline, caudal posterior parietal, and extrastriate areas. Statistical analyses revealed that the pattern of connections of area 8C is more akin to that characterizing a premotor area, rather than a prefrontal area. We conclude that cytoarchitectural area 6Va in the marmoset is similar to ventral premotor areas identified in other simian primates, and that area 8C corresponds to a specialized subdivision of the caudal premotor complex where visual information for the guidance of movements is likely to be emphasized. J. Comp. Neurol. 523:1222–1247, 2015. © 2015 Wiley Periodicals, Inc.     

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan

Glucose transporter type I deficiency syndrome (GLUT1DS) is an encephalopathic disorder due to a chronic insufficient transport of glucose into the brain. PET studies in GLUT1DS documented a widespread cortico‐thalamic hypometabolism and a signal increase in the basal ganglia, regardless of age and clinical phenotype. Herein, we captured the pattern of functional connectivity of distinct striatal, cortical, and cerebellar regions in GLUT1DS (10 children, eight adults) and in healthy controls (HC, 19 children, 17 adults) during rest. Additionally, we explored for regional connectivity differences in GLUT1 children versus adults and according to the clinical presentation. Compared to HC, GLUT1DS exhibited increase connectivity within the basal ganglia circuitries and between the striatal regions with the frontal cortex and cerebellum. The excessive connectivity was predominant in patients with movement disorders and in children compared to adults, suggesting a correlation with the clinical phenotype and age at fMRI study. Our findings highlight the primary role of the striatum in the GLUT1DS pathophysiology and confirm the dependency of symptoms to the patients' chronological age. Despite the reduced chronic glucose uptake, GLUT1DS exhibit increased connectivity changes in regions highly sensible to glycopenia. Our results may portrait the effect of neuroprotective brain strategy to overcome the chronic poor energy supply during vulnerable ages.     

Thalamic connections of the primary motor cortex (M1) of owl monkeys

To determine the relative contributions of transthalamic cerebellar and pallidal projections to the primary motor cortex (M1) of owl monkeys, we examined the thalamic labeling resulting from injections of fluorescent tracers and wheatgerm agglutinin/horseradish peroxidase conjugate (WGA-HRP) into regions of M1 identified by intracortical microstimulation. Injections were placed in the major somatotopic divisions of M1 (the hindlimb, trunk, forelimb, and face representations) and in the caudal and rostral M1 subareas. In most cases, we injected several differentiable tracers into different parts of M1. Our results indicate that the strongest connections of M1 are with subdivisions of the ventral lateral thalamus (VL); other connections are mainly with intralaminar nuclei (the central lateral, paracentral, and center median nuclei) and the reticular nucleus. Most projections are reciprocal and topographically organized. M1 is strongly connected with the principal (VLp), medial (VLx), and anterior (VLa) subdivisions of the VL complex but has at most weak connections with the dorsal division (VLd). Each of the major somatotopic divisions of M1 is connected with an anteroposteriorly elongated territory within the VL complex. The connections are somatotopically organized such that the M1 hindlimb representation is connected with a band of cells in the lateral and anterior portions of the VL complex (spanning VLa and VLp), whereas the trunk, forelimb, and face representations are connected with successively more medially and posteriorly situated cell bands (spanning VLa, VLp, and VLx). There is some degree of overlap between the somatotopic territories within VL, although the absence of double-labeled cells in cases with injections of adjacent somatotopic divisions of M1 suggests that individual thalamic neurons project to single somatotopic regions. In addition to somatotopic differences, the connections of the caudal and rostral subdivisions of M1 differ to some extent. Caudal M1 is connected most strongly with VLp, a target of cerebellar projections, but it is also connected with VLa, which receives pallidal inputs. In complementary fashion, rostral M1 is most strongly connected with VLa, but it is also connected with VLp. VLx, a target of cerebellar projections, has significant connections with both caudal and rostral M1. These results indicate that all parts of M1 are influenced by both the cerebellum and globus pallidus in owl monkeys, as has been suggested in some recent studies of macaque monkeys. © 1994 Wiley-Liss, Inc.