There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these ...subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.
In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.
These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.
Rates of depression and addiction have risen drastically over the past decade, but the lack of integrative techniques remains a barrier to accurate diagnoses of these mental illnesses. Changes in ...reward/aversion behavior and corresponding brain structures have been identified in those with major depressive disorder (MDD) and cocaine-dependence polysubstance abuse disorder (CD). Assessment of statistical interactions between computational behavior and brain structure may quantitatively segregate MDD and CD.
Here, 111 participants 40 controls (CTRL), 25 MDD, 46 CD underwent structural brain MRI and completed an operant keypress task to produce computational judgment metrics. Three analyses were performed: (1) linear regression to evaluate groupwise (CTRL v. MDD v. CD) differences in structure-behavior associations, (2) qualitative and quantitative heatmap assessment of structure-behavior association patterns, and (3) the k-nearest neighbor machine learning approach using brain structure and keypress variable inputs to discriminate groups.
This study yielded three primary findings. First, CTRL, MDD, and CD participants had distinct structure-behavior linear relationships, with only 7.8% of associations overlapping between any two groups. Second, the three groups had statistically distinct slopes and qualitatively distinct association patterns. Third, a machine learning approach could discriminate between CTRL and CD, but not MDD participants.
These findings demonstrate that variable interactions between computational behavior and brain structure, and the patterns of these interactions, segregate MDD and CD. This work raises the hypothesis that analysis of interactions between operant tasks and structural neuroimaging might aide in the objective classification of MDD, CD and other mental health conditions.
Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such ...as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.
The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a ...large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T
-weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant (
< 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant (
< 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates (
< 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.
Background Reinforcement of behavioral responses involves a complex cerebral circuit engaging specific neuronal networks that are modulated by cortical oversight systems affiliated with emotion, ...memory, judgment, and decision making (collectively referred to in this study as the “extended reward and oversight system” or “reward network”). We examined whether reward-network brain volumes are reduced in alcoholics and how volumes of subcomponents within this system are correlated with memory and drinking history. Methods Morphometric analysis was performed on magnetic resonance brain scans in 21 abstinent long-term chronic alcoholic men and 21 healthy control men, group-matched on age, verbal IQ, and education. We derived volumes of total brain and volumes of cortical and subcortical reward-related structures including the dorsolateral-prefrontal, orbitofrontal, cingulate cortices, and the insula, as well as the amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon. Results Morphometric analyses of reward-related regions revealed decreased total reward-network volume in alcoholic subjects. Volume reduction was most pronounced in right dorsolateral-prefrontal cortex, right anterior insula, and right NAc, as well as left amygdala. In alcoholics, NAc and anterior insula volumes increased with length of abstinence, and total reward-network and amygdala volumes correlated positively with memory scores. Conclusions The observation of decreased reward-network volume suggests that alcoholism is associated with alterations in this neural reward system. These structural reward system deficits and their correlation with memory scores elucidate underlying structural-functional relationships between alcoholism and emotional and cognitive processes.
Contact sports participation has been shown to have both beneficial and detrimental effects on health, however little is known about the metabolic sequelae of these effects. We aimed to identify ...metabolite alterations across a collegiate American football season. Serum was collected from 23 male collegiate football athletes before the athletic season (Pre) and after the last game (Post). Samples underwent nontargeted metabolomic profiling and 1131 metabolites were included for univariate, pathway enrichment, and multivariate analyses. Significant metabolites were assessed against head acceleration events (HAEs). 200 metabolites changed from Pre to Post (P < 0.05 and Q < 0.05); 160 had known identity and mapped to one of 57 pre-defined biological pathways. There was significant enrichment of metabolites belonging to five pathways (P < 0.05): xanthine, fatty acid (acyl choline), medium chain fatty acid, primary bile acid, and glycolysis, gluconeogenesis, and pyruvate metabolism. A set of 12 metabolites was sufficient to discriminate Pre from Post status, and changes in 64 of the 200 metabolites were also associated with HAEs (P < 0.05). In summary, the identified metabolites, and candidate pathways, argue there are metabolic consequences of both physical training and head impacts with football participation. These findings additionally identify a potential set of objective biomarkers of repetitive head injury.
The relationship of human brain structure to cognitive function is complex, and how this relationship differs between childhood and adulthood is poorly understood. One strong hypothesis suggests the ...cognitive function of Fluid Intelligence (Gf) is dependent on prefrontal cortex and parietal cortex. In this work, we developed a novel graph convolutional neural networks (gCNNs) for the analysis of localized anatomic shape and prediction of Gf. Morphologic information of the cortical ribbons and subcortical structures was extracted from T1-weighted MRIs within two independent cohorts, the Adolescent Brain Cognitive Development Study (ABCD; age: 9.93 ± 0.62 years) of children and the Human Connectome Project (HCP; age: 28.81 ± 3.70 years). Prediction combining cortical and subcortical surfaces together yielded the highest accuracy of Gf for both ABCD (R = 0.314) and HCP datasets (R = 0.454), outperforming the state-of-the-art prediction of Gf from any other brain measures in the literature. Across both datasets, the morphology of the amygdala, hippocampus, and nucleus accumbens, along with temporal, parietal and cingulate cortex consistently drove the prediction of Gf, suggesting a significant reframing of the relationship between brain morphology and Gf to include systems involved with reward/aversion processing, judgment and decision-making, motivation, and emotion.
Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial “prospect” (expectancy) ...phase, when a set of three monetary amounts was displayed, and a subsequent “outcome” phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.
Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and ...subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB).
We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.
These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.
Cortico-striato-thalamo-cortical (CSTC) loops are fundamental organizing units in mammalian brains. CSTCs process limbic, associative, and sensorimotor information in largely separated but ...interacting networks. CTSC loops pass through paired striatal compartments, striosome (aka patch) and matrix, segregated pools of medium spiny projection neurons with distinct embryologic origins, cortical/subcortical structural connectivity, susceptibility to injury, and roles in behaviors and diseases. Similarly, striatal dopamine modulates activity in striosome and matrix in opposite directions. Routing CSTCs through one compartment may be an anatomical basis for regulating discrete functions. We used differential structural connectivity, identified through probabilistic diffusion tractography, to distinguish the striatal compartments (striosome-like and matrix-like voxels) in living humans. We then mapped compartment-specific projections and quantified structural connectivity between each striatal compartment, the globus pallidus interna (GPi), and 20 thalamic nuclei in 221 healthy adults. We found that striosome-originating and matrix-originating streamlines were segregated within the GPi: striosome-like connectivity was significantly more rostral, ventral, and medial. Striato-pallido-thalamic streamline bundles that were seeded from striosome-like and matrix-like voxels transited spatially distinct portions of the white matter. Matrix-like streamlines were 5.7-fold more likely to reach the GPi, replicating animal tract-tracing studies. Striosome-like connectivity dominated in six thalamic nuclei (anteroventral, central lateral, laterodorsal, lateral posterior, mediodorsal-medial, and medial geniculate). Matrix-like connectivity dominated in seven thalamic nuclei (centromedian, parafascicular, pulvinar-anterior, pulvinar-lateral, ventral lateral-anterior, ventral lateral-posterior, ventral posterolateral). Though we mapped all thalamic nuclei independently, functionally-related nuclei were matched for compartment-level bias. We validated these results with prior thalamostriate tract tracing studies in non-human primates and other species; where reliable data was available, all agreed with our measures of structural connectivity. Matrix-like connectivity was lateralized (left > right hemisphere) in 18 thalamic nuclei, independent of handedness, diffusion protocol, sex, or whether the nucleus was striosome-dominated or matrix-dominated. Compartment-specific biases in striato-pallido-thalamic structural connectivity suggest that routing CSTC loops through striosome-like or matrix-like voxels is a fundamental mechanism for organizing and regulating brain networks. Our MRI-based assessments of striato-thalamic connectivity in humans match and extend the results of prior tract tracing studies in animals. Compartment-level characterization may improve localization of human neuropathologies and improve neurosurgical targeting in the GPi and thalamus.
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