Putamen volume predicts real-time fMRI neurofeedback learning success across paradigms and neurofeedback target regions.

Real-time fMRI guided neurofeedback training has gained increasing interest as a noninvasive brain regulation technique with the potential to modulate functional brain alterations in therapeutic contexts. Individual variations in learning success and treatment response have been observed, yet the neural substrates underlying the learning of self-regulation remain unclear. Against this background, we explored potential brain structural predictors for learning success with pooled data from three real-time fMRI data sets. Our analysis revealed that gray matter volume of the right putamen could predict neurofeedback learning success across the three data sets (n = 66 in total). Importantly, the original studies employed different neurofeedback paradigms during which different brain regions were trained pointing to a general association with learning success independent of specific aspects of the experimental design. Given the role of the putamen in associative learning this finding may reflect an important role of instrumental learning processes and brain structural variations in associated brain regions for successful acquisition of fMRI neurofeedback-guided self-regulation.

The topology of higher-order complexes associated with brain hubs in human connectomes.

Higher-order connectivity in complex systems described by simplexes of different orders provides a geometry for simplex-based dynamical variables and interactions. Simplicial complexes that constitute a functional geometry of the human connectome can be crucial for the brain complex dynamics. In this context, the best-connected brain areas, designated as hub nodes, play a central role in supporting integrated brain function. Here, we study the structure of simplicial complexes attached to eight global hubs in the female and male connectomes and identify the core networks among the affected brain regions. These eight hubs (Putamen, Caudate, Hippocampus and Thalamus-Proper in the left and right cerebral hemisphere) are the highest-ranking according to their topological dimension, defined as the number of simplexes of all orders in which the node participates. Furthermore, we analyse the weight-dependent heterogeneity of simplexes. We demonstrate changes in the structure of identified core networks and topological entropy when the threshold weight is gradually increased. These results highlight the role of higher-order interactions in human brain networks and provide additional evidence for (dis)similarity between the female and male connectomes.

Microneuroanatomy of the Anterior Frontal Laser Trajectory to the Insula.

BACKGROUND: Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an emerging minimally invasive procedure for the treatment of deep intracranial lesions. Insular lesions are challenging to treat because of the risk of damaging important surrounding structures. The precise knowledge of the neural structures that are at risk along the trajectory and during the ablation is essential to reduce associated complications. This study aims to describe the relevant anatomy of the anterior frontal LITT trajectory to the insular region by using sectional anatomy and fiber dissection technique. METHODS: Three silicone-injected cadaveric heads were used to implant laser catheters bilaterally to the insular region by using a frameless stereotactic technique from a frontal approach. Sections were cut in both the oblique axial plane parallel to the trajectory and in the coronal plane. White matter fiber dissections were used to establish the tracts related to the laser trajectory from lateral to medial and medial to lateral. RESULTS: Supraorbital regions were selected as entry points. After crossing the frontal bone, the track intersected the inferior frontal lobe. The catheter was illustrated reaching the insular region medial to the inferior fronto-occipital fasciculus and insular cortex, and superior to the uncinate fasciculus. The uncinate fasciculus, extreme capsule, claustrum, external capsule, and putamen were traversed, preserving the major vascular structures. CONCLUSIONS: Independent of the insular area treated, an understanding of the neuroanatomy related to the anterior frontal laser trajectory is essential to improve the ability to perform LITT of this challenging region.

Shape-related characteristics of age-related differences in subcortical structures.

OBJECTIVES: With an increasing aging population, it is important to understand biological markers of aging. Subcortical volume is known to differ with age; additionally considering shape-related characteristics may provide a better index of age-related differences. Fractal dimensionality is more sensitive to age-related differences, but is borne out of mathematical principles, rather than neurobiological relevance. We considered four distinct measures of shape and how they relate to aging and fractal dimensionality: surface-to-volume ratio, sphericity, long-axis curvature, and surface texture. METHODS: Structural MRIs from a combined sample of over 600 healthy adults were used to measure age-related differences in the structure of the thalamus, putamen, caudate, and hippocampus. For each, volume and fractal dimensionality were calculated, as well as four distinct shape measures. These measures were examined for their utility in explaining age-related variability in brain structure. RESULTS: The four shape measures were able to account for 80%-90% of the variance in fractal dimensionality. Of the distinct shape measures, surface-to-volume ratio was the most sensitive biomarker. CONCLUSION: Though volume is often used to characterize inter-individual differences in subcortical structures, our results demonstrate that additional measures can be useful complements. Our results indicate that shape characteristics are useful biological markers of aging.

Immersive bilingualism reshapes the core of the brain.

Bilingualism has been shown to affect the structure of the brain, including cortical regions related to language. Less is known about subcortical structures, such as the basal ganglia, which underlie speech monitoring and language selection, processes that are crucial for bilinguals, as well as other linguistic functions, such as grammatical and phonological acquisition and processing. Simultaneous bilinguals have demonstrated significant reshaping of the basal ganglia and the thalamus compared to monolinguals. However, it is not clear whether these effects are due to learning of the second language (L2) at a very young age or simply due to continuous usage of two languages. Here, we show that bilingualism-induced subcortical effects are directly related to the amount of continuous L2 usage, or L2 immersion. We found significant subcortical reshaping in non-simultaneous (or sequential) bilinguals with extensive immersion in a bilingual environment, closely mirroring the recent findings in simultaneous bilinguals. Importantly, some of these effects were positively correlated to the amount of L2 immersion. Conversely, sequential bilinguals with comparable proficiency and age of acquisition (AoA) but limited immersion did not show similar effects. Our results provide structural evidence to suggestions that L2 acquisition continuously occurs in an immersive environment, and is expressed as dynamic reshaping of the core of the brain. These findings propose that second language learning in the brain is a dynamic procedure which depends on active and continuous L2 usage.

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

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

Evaluating volumetric brain registration performance using structural connectivity information.

In this paper, we propose a pipeline for evaluating the performance of brain image registration methods. Our aim is to compare how well the algorithms align subtle functional/anatomical boundaries that are not easily detectable in T1- or T2-weighted magnetic resonance images (MRI). In order to achieve this, we use structural connectivity information derived from diffusion-weighted MRI data. We demonstrate the approach by looking into how two competing registration algorithms perform at aligning fine-grained parcellations of subcortical structures. The results show that the proposed evaluation framework can offer new insights into the performance of registration algorithms in brain regions with highly varied structural connectivity profiles.

Top-down and bottom-up modulation of brain structures involved in auditory discrimination.

Auditory deviancy detection comprises both automatic and voluntary processing. Here, we investigated the neural correlates of different components of the sensory discrimination process using functional magnetic resonance imaging. Subliminal auditory processing of deviant events that were not detected led to activation in left superior temporal gyrus. On the other hand, both correct detection of deviancy and false alarms activated a frontoparietal network of attentional processing and response selection, i.e. this network was activated regardless of the physical presence of deviant events. Finally, activation in the putamen, anterior cingulate and middle temporal cortex depended on factual stimulus representations and occurred only during correct deviancy detection. These results indicate that sensory discrimination may rely on dynamic bottom-up and top-down interactions.

Improved segmentation of deep brain grey matter structures using magnetization transfer (MT) parameter maps.

Basal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological and neuropsychiatric disorders. Currently available structural T1-weighted (T1w) magnetic resonance images do not provide sufficient contrast for reliable automated segmentation of various subcortical grey matter structures. We use a novel, semi-quantitative magnetization transfer (MT) imaging protocol that overcomes limitations in T1w images, which are mainly due to their sensitivity to the high iron content in subcortical grey matter. We demonstrate improved automated segmentation of putamen, pallidum, pulvinar and substantia nigra using MT images. A comparison with segmentation of high-quality T1w images was performed in 49 healthy subjects. Our results show that MT maps are highly suitable for automated segmentation, and so for multi-subject morphometric studies with a focus on subcortical structures.

Volume and iron content in basal ganglia and thalamus.

Magnetic resonance imaging (MRI) studies have highlighted the possibility to investigate brain iron content in vivo. In this study, we combined T2* relaxometry and automatic segmentation of basal ganglia based on T1-weighted images in healthy subjects, with the aim of characterizing age related changes in volume and iron-related relaxivity values (R2*) of these structures. Thirty healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes were calculated for the selected subcortical structures (pallidum, putamen, thalamus and caudate nucleus). Our results showed a correlation between R2* values and iron concentration as calculated from published post-mortem data. Furthermore, we observed a shrinkage/iron increase with a different pattern in the anatomical regions selected in this work, suggesting that the age-related changes on these MR parameters are specific to the subcortical structure considered. In particular, the putamen demonstrated a decrease of volume and an increase of iron level, with the posterior region of this structure appearing more disposed to iron deposition. Our work suggests that combining volumetry and iron estimation in MRI permits to investigate in vivo neurophysiological and neuropathological changes of basal ganglia.

Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus.

The basal ganglia and thalamus are involved in processing all physiological behaviors and affected by many diseases. Accurate localization is a crucial issue in neuroimaging, particularly when working with groups of normalized images in a standard stereotaxic space. Here, manual delineation of the central structures (thalamus; nucleus caudatus and accumbens; putamen, pallidum, substantia nigra) was performed on 30 high resolution MRIs of healthy young adults (15 female, median age 31 years) in native space. Protocol inter-rater reliabilities were quantified as structure overlap (similarity indices, SIs). Structural volumes were calculated in native space, and after spatial normalization to stereotaxic space (MNI/ICBM152) and in relation to hemispheric volumes. Spatial extents relative to the anterior commissure (AC) were extracted. The 30 resulting atlases were then used to create probabilistic maps in stereotaxic space. Inter-rater SIs were high at 0.85-0.92 except for the nucleus accumbens. In native space, caudate, nucleus accumbens and putamen were significantly larger on the left, and the globus pallidus larger in males. After normalizing for brain volume, the nucleus accumbens, putamen and thalamus were larger on the left, with the gender difference in the globus pallidus still detectable. Some of these volume differences translated into significantly different distances from the AC. The probabilistic maps showed that overall the central structures' boundaries are relatively unchanged after spatial normalization. We present a comprehensive assessment of thalamic and basal ganglia volumetric and geometric data in both native and stereotaxic spaces. Probabilistic maps in MNI/ICBM152 space will allow accurate localization in group analyses.

A Bayesian framework for global tractography.

We readdress the diffusion tractography problem in a global and probabilistic manner. Instead of tracking through local orientations, we parameterise the connexions between brain regions at a global level, and then infer on global and local parameters simultaneously in a Bayesian framework. This approach offers a number of important benefits. The global nature of the tractography reduces sensitivity to local noise and modelling errors. By constraining tractography to ensure a connexion is found, and then inferring on the exact location of the connexion, we increase the robustness of connectivity-based parcellations, allowing parcellations of connexions that were previously invisible to tractography. The Bayesian framework allows a direct comparison of the evidence for connecting and non-connecting models, to test whether the connexion is supported by the data. Crucially, by explicit parameterisation of the connexion between brain regions, we infer on a parameter that is shared with models of functional connectivity. This model is a first step toward the joint inference on functional and anatomical connectivity.

Fronto-striatal connections in the human brain: a probabilistic diffusion tractography study.

Anatomical studies in animals have described multiple striatal circuits and suggested that sub-components of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain, we used Diffusion Tensor Imaging (DTI) tractography to reconstruct neural connections between the frontal cortex and the caudate nucleus and putamen in vivo. We demonstrate that the human caudate nucleus is interconnected with the prefrontal cortex, inferior and middle temporal gyrus, frontal eye fields, cerebellum and thalamus; the putamen is interconnected with the prefrontal cortex, primary motor area, primary somatosensory cortex, supplementary motor area, premotor area, cerebellum and thalamus. A connectivity-based seed classification analysis identified connections between the dorsolateral prefrontal areas (DLPFC) and the dorsal-posterior caudate nucleus and between the ventrolateral prefrontal areas (VLPFC) and the ventral-anterior caudate nucleus. For the putamen, connections exist between the supplementary motor area (SMA) and dorsal-posterior putamen while the premotor area projects to medial putamen, and the primary motor area to the lateral putamen. Identifying the anatomical organization of the fronto-striatal network has important implications for understanding basal ganglia function and associated disease processes.

Somatotopically arranged inputs from putamen and subthalamic nucleus to primary motor cortex.

Employing retrograde transsynaptic transport of rabies virus, we investigated the organization of basal ganglia inputs to hindlimb, proximal and distal forelimb, and orofacial representations of the macaque primary motor cortex (MI). Four days after rabies injections into these MI regions, neuronal labeling occurred in the striatum and the subthalamic nucleus (STN) through the cortico-basal ganglia loop circuits. In the striatum, two distinct sets of the labeling were observed: one in the dorsal putamen, and the other in the ventral striatum (ventromedial putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically arranged and its distribution pattern was in good accordance with that of the corticostriatal inputs, such that the hindlimb, orofacial, or forelimb area was located in the dorsal, ventral, or intermediate zone of the putamen, respectively. The distribution pattern of the ventral striatal labeling was essentially the same in all cases. In the STN, the somatotopic arrangement of labeled neurons was in register with that of corticosubthalamic inputs. The present results suggest that the cortico-basal ganglia motor circuits involving the dorsal putamen and the STN may constitute separate closed loops based on the somatotopy, while the ventral striatum provides common multisynaptic projections to all body-part representations in the MI.

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder.

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.

Subcortical, cerebellar, and magnetic resonance based consistent brain image registration.

A new landmark-initialized segmentation and intensity-based (LI-SI) inverse-consistent linear elastic image registration algorithm is presented. This method uses manually identified landmarks, segmented volumetric (anatomical) structures, and normalized image signal intensity information to coregister datasets. The features used for image registration and evaluation include 35 cortical, cerebellar, and commissure landmarks manually identified by experts, subcortical and cerebellar regions defined semi-automatically by an artificial neural network and manually trimmed for validity by experts, and tissue classified images that were generated using a discriminant analysis of three magnetic resonance image sets representing T1, T2, and PD modalities. Four groups of results were computed for coregistering 16 datasets with the following registration techniques: rigid registration, extended Talairach registration, intensity-only inverse-consistent linear elastic registration, and the new LI-SI registration. Results are presented showing that relative overlap measurements increased as the dimensionality of the registration algorithm and amount of anatomical information increased. The average relative overlap improved from 0.53 for the rigid registration to 0.55 for the Talairach registration to 0.74 for the intensity-only and to 0.85 for the LI-SI algorithm. We showed a statistically significant improvement for all but one structure using the intensity-only algorithm compared to the Talairach registration. Furthermore, statistically significant improvements for all structures were achieved using the LI-SI algorithm compared to the intensity-only algorithm.

Reappraisal of the motor role of basal ganglia: a functional magnetic resonance image study.

The importance of the basal ganglia in controlling motor function is well known. However, neuroimaging studies have failed to show either movement-rate dependence or different activation patterns caused by self-initiated (SI) and externally triggered (ET) movements in the basal ganglia-thalamo-motor loop. We herein report the functional magnetic resonance image (fMRI) mapping of sequential left-hand finger movements at five different rates under SI and ET conditions. Significant movement-rate dependence was found in the whole right basal ganglia-thalamo-motor loop only during the SI task. Network analysis also showed strong interactions within this loop during SI movement, whereas interactions were present only from the premotor cortex to the putamen via the sensorimotor cortex during the ET task. Furthermore, psychophysiological interaction analysis confirmed the different modulation between the two tasks in the putamen. fMRI provides evidence that the basal ganglia-thalamo-motor loop plays a key role in controlling the rate of sequential finger movements in SI movement but not in ET movement.

Early setting of grammatical processing in the bilingual brain.

The existence of a "critical period" for language acquisition is controversial. Bilingual subjects with variable age of acquisition (AOA) and proficiency level (PL) constitute a suitable model to study this issue. We used functional magnetic resonance imaging to investigate the effects of AOA and PL on neural correlates of grammatical and semantic judgments in Italian-German bilinguals who learned the second language at different ages and had different proficiency levels. While the pattern of brain activity for semantic judgment was largely dependent on PL, AOA mainly affected the cortical representation of grammatical processes. These findings support the view that both AOA and PL affect the neural substrates of second language processing, with a differential effect on grammar and semantics.

Dissociable executive functions in the dynamic control of behavior: inhibition, error detection, and correction.

The present study employed event-related fMRI and EEG to investigate the biological basis of the cognitive control of behavior. Using a GO/NOGO task optimized to produce response inhibitions, frequent commission errors, and the opportunity for subsequent behavioral correction, we identified distinct cortical areas associated with each of these specific executive processes. Two cortical systems, one involving right prefrontal and parietal areas and the second regions of the cingulate, underlay inhibitory control. The involvement of these two systems was predicated upon the difficulty or urgency of the inhibition and each was employed to different extents by high- and low-absent-minded subjects. Errors were associated with medial activation incorporating the anterior cingulate and pre-SMA while behavioral alteration subsequent to errors was associated with both the anterior cingulate and the left prefrontal cortex. Furthermore, the EEG data demonstrated that successful response inhibition depended upon the timely activation of cortical areas as predicted by race models of response selection. The results highlight how higher cognitive functions responsible for behavioral control can result from the dynamic interplay of distinct cortical systems.

Automatic segmentation of subcortical brain structures in MR images using information fusion.

This paper reports a new automated method for the segmentation of internal cerebral structures using an information fusion technique. The information is provided both by images and expert knowledge, and consists in morphological, topological, and tissue constitution data. All this ambiguous, complementary and redundant information is managed using a three-step fusion scheme based on fuzzy logic. The information is first modeled into a common theoretical frame managing its imprecision and incertitude. The models are then fused and a decision is taken in order to reduce the imprecision and to increase the certainty in the location of the structures. The whole process is illustrated on the segmentation of thalamus, putamen, and head of the caudate nucleus from expert knowledge and magnetic resonance images, in a protocol involving 14 healthy volunteers. The quantitative validation is achieved by comparing computed, manually segmented structures and published data by means of indexes assessing the accuracy of volume estimation and spatial location. Results suggest a consistent volume estimation with respect to the expert quantification and published data, and a high spatial similarity of the segmented and computed structures. This method is generic and applicable to any structure that can be defined by expert knowledge and morphological images.