R2* and quantitative susceptibility mapping in deep gray matter of 498 healthy controls from 5 to 90 years

Putative MRI markers of iron in deep gray matter have demonstrated age related changes during discrete periods of healthy childhood or adulthood, but few studies have included subjects across the lifespan. This study reports both transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) of four primary deep gray matter regions (thalamus, putamen, caudate, and globus pallidus) in 498 healthy individuals aged 5–90 years. In the caudate, putamen, and globus pallidus, increases of QSM and R2* were steepest during childhood continuing gradually throughout adulthood, except caudate susceptibility which reached a plateau in the late 30s. The thalamus had a unique profile with steeper changes of R2* (reflecting additive effects of myelin and iron) than QSM during childhood, both reaching a plateau in the mid‐30s to early 40s and decreasing thereafter. There were no hemispheric or sex differences for any region. Notably, both R2* and QSM values showed more inter‐subject variability with increasing age from 5 to 90 years, potentially reflecting a common starting point in iron/myelination during childhood that diverges as a result of lifestyle and genetic factors that accumulate with age.     

Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI

Increased brain iron concentration is often reported concurrently with disease development in multiple sclerosis (MS) and other neurodegenerative diseases. However, it is unclear whether the higher iron concentration in patients stems from an influx of iron into the tissue or a relative reduction in tissue compartments without much iron. By taking into account structural volume, we investigated tissue iron content in the deep gray matter (DGM) over 2 years, and compared findings to previously reported changes in iron concentration. 120 MS patients and 40 age‐ and sex‐matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after 2 years. Overall, iron content was calculated from structural MRI and quantitative susceptibility mapping in the thalamus, caudate, putamen, and globus pallidus. MS patients had significantly lower iron content than controls in the thalamus, with progressive MS patients demonstrating lower iron content than relapsing–remitting patients. Over 2 years, iron content decreased in the DGM of patients with MS, while it tended to increase or remain stable among controls. In the thalamus, decreasing iron content over 2 years was associated with disability progression. Our study showed that temporally increasing magnetic susceptibility in MS should not be considered as evidence for iron influx because it may be explained, at least partially, by disease‐related atrophy. Declining DGM iron content suggests that, contrary to the current understanding, iron is being removed from the DGM in patients with MS.     

Altered single‐subject gray matter structural networks in drug‐naïve attention deficit hyperactivity disorder children

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug‐naïve children with ADHD and 83 age‐matched healthy controls. Single‐subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug‐naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.     

Beware of white matter hyperintensities causing systematic errors in FreeSurfer gray matter segmentations!

Volumetric estimates of subcortical and cortical structures, extracted from T1‐weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer gray matter (GM) structure volumes and its possible bias on functional relationships. T1‐weighted images from 1,077 participants (4,321 timepoints) from the Alzheimer''s Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2‐weighted or Fluid‐attenuated inversion recovery images. Mixed‐effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overall WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance. Participants with higher WMH volumes had higher overlaps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (p < .0001). When not corrected for WMHs, caudate volumes increased with age (p < .0001) and were not different between cognitively healthy individuals and age‐matched probable Alzheimer''s disease patients. After correcting for WMHs, caudate volumes decreased with age (p < .0001), and Alzheimer''s disease patients had lower caudate volumes than cognitively healthy individuals (p < .01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (p < .0001). Presence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.     

Neuroimaging measures of iron and gliosis explain memory performance in aging

Evidence from animal and histological studies has indicated that accumulation of iron in the brain results in reactive gliosis that contributes to cognitive deficits. The current study extends these findings to human cognitive aging and suggests that magnetic resonance imaging (MRI) techniques like quantitative relaxometry can be used to study iron and its effects in vivo. The effects of iron on microstructure and memory performance were examined using a combination of quantitative relaxometry and multicompartment diffusion imaging in 35 young (21.06 ± 2.18 years) and 28 older (72.58 ± 6.47 years) adults, who also completed a memory task. Replicating past work, results revealed age‐related increases in iron content (R2*) and diffusion, and decreases in memory performance. Independent of age group, iron content was significantly related to restricted (intracellular) diffusion in regions with low‐moderate iron (hippocampus, caudate) and to all diffusion metrics in regions with moderate‐high iron (putamen, globus pallidus). This pattern is consistent with different stages of iron‐related gliosis, ranging from astrogliosis that may influence intracellular diffusion to microglial proliferation and increased vascular permeability that may influence all sources of diffusion. Further, hippocampal restricted diffusion was significantly related to memory performance, with a third of this effect related to iron content; consistent with the hypothesis that higher iron‐related astrogliosis in the hippocampus is associated with poorer memory performance. These results demonstrate the sensitivity of MRI to iron‐related gliosis and extend our understanding of its impact on cognition by showing that this relationship also explains individual differences in memory performance.     

Modulation effect of substantia nigra iron deposition and functional connectivity on putamen glucose metabolism in Parkinson's disease

Neurodegeneration of the substantia nigra affects putamen activity in Parkinson''s disease (PD), yet in vivo evidence of how the substantia nigra modulates putamen glucose metabolism in humans is missing. We aimed to investigate how substantia nigra modulates the putamen glucose metabolism using a cross‐sectional design. Resting‐state fMRI, susceptibility‐weighted imaging, and [¹⁸F]‐fluorodeoxyglucose‐PET (FDG‐PET) data were acquired. Forty‐two PD patients and 25 healthy controls (HCs) were recruited for simultaneous PET/MRI scanning. The main measurements of the current study were R2* images representing iron deposition (28 PD and 25 HCs), standardized uptake value ratio (SUVr) images representing FDG‐uptake (33 PD and 25 HCs), and resting state functional connectivity maps from resting state fMRI (34 PD and 25 HCs). An interaction term based on the general linear model was used to investigate the joint modulation effect of nigral iron deposition and nigral‐putamen functional connectivity on putamen FDG‐uptake. Compared with HCs, we found increased iron deposition in the substantia nigra (p = .007), increased FDG‐uptake in the putamen (left: P _FWE < 0.001; right: P _FWE < 0.001), and decreased functional connectivity between the substantia nigra and the anterior putamen (left P _FWE < 0.001, right: P _FWE = 0.007). We then identified significant interaction effect of nigral iron deposition and nigral‐putamen connectivity on FDG‐uptake in the putamen (p = .004). The current study demonstrated joint modulation effect of the substantia nigra iron deposition and nigral‐putamen functional connectivity on putamen glucose metabolic distribution, thereby revealing in vivo pathological mechanism of nigrostriatal neurodegeneration of PD.     

Functional correlates of motor control impairments in multiple sclerosis: A 7 Tesla task functional MRI study

Upper and lower limb impairments are common in people with multiple sclerosis (pwMS), yet difficult to clinically identify in early stages of disease progression. Tasks involving complex motor control can potentially reveal more subtle deficits in early stages, and can be performed during functional MRI (fMRI) acquisition, to investigate underlying neural mechanisms, providing markers for early motor progression. We investigated brain activation during visually guided force matching of hand or foot in 28 minimally disabled pwMS (Expanded Disability Status Scale (EDSS) < 4 and pyramidal and cerebellar Kurtzke Functional Systems Scores ≤ 2) and 17 healthy controls (HC) using ultra‐high field 7‐Tesla fMRI, allowing us to visualise sensorimotor network activity in high detail. Task activations and performance (tracking lag and error) were compared between groups, and correlations were performed. PwMS showed delayed (+124 s, p = .002) and more erroneous (+0.15 N, p = .001) lower limb tracking, together with lower cerebellar, occipital and superior parietal cortical activation compared to HC. Lower activity within these regions correlated with worse EDSS (p = .034), lower force error (p = .006) and higher lesion load (p < .05). Despite no differences in upper limb task performance, pwMS displayed lower inferior occipital cortical activation. These results demonstrate that ultra‐high field fMRI during complex hand and foot tracking can identify subtle impairments in lower limb movements and upper and lower limb brain activity, and differentiates upper and lower limb impairments in minimally disabled pwMS.     

Quantitative assessment of subcortical atrophy and iron content in progressive supranuclear palsy and parkinsonian variant of multiple system atrophy

It is a matter of debate whether increased brain iron levels are the cause or only the consequence of neurodegenerative process in degenerative parkinsonism. The aim of this study is to characterize disease-related changes in volumes and iron-related R2* values of basal ganglia and thalamus. 13 patients with progressive supranuclear palsy (PSP), 15 with a parkinsonian variant of multiple system atrophy (MSA-p), 29 with Parkinson’s disease (PD), and 21 age-matched controls underwent 3-Tesla MRI. The R2* values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. Voxel-based analysis was also performed to visualize a topographical correlation of R2* value and volume. The PSP group had significantly higher R2* values in globus pallidus and caudate nucleus (p < 0.05), whereas the MSA-p group had higher R2* values in putamen (p < 0.001) than PD and controls. The globus pallidus in PSP and the putamen in MSA-p were the most significant areas of atrophy to differentiate PSP, MSA-p and PD (AUC = 0.856, 0.832, respectively, p < 0.001). The R2* values in both structures increased in parallel with the extent of atrophy. They were negatively correlated with volumes in putamen (r = ?0.777, p < 0.001) and globus pallidus (r = ?0.409, p = 0.025) of MSA-p, and globus pallidus (r = ?0.4, p = 0.043) of PSP. Voxel-based analysis identified higher R2* values in more severely atrophic sub-regions in these structures. We observed topographical differences of iron deposition as well as atrophy between MSA-p and PSP. Increased iron levels were related to the structural atrophy in basal ganglia. Our results imply that iron accumulation is likely an epiphenomenon of the degenerative process.     

Diffusion tensor imaging of deep gray matter in children treated for brain malignancies

Purpose

Previous DTI studies reported microstructural changes in white matter of patients receiving treatment for brain malignancies. The primary aim of this prospective pilot longitudinal study was to examine if DTI can detect microstructural changes in deep gray matter (as evaluated by the apparent diffusion coefficient, ADC) between pediatric patients treated with cranial radiation therapy and typically developing healthy children. The relationship between ADC and neurobehavioral performance was also examined.

Methods

ADC was measured at 1.5 T in the caudate, putamen, globus pallidus, thalamus, and hippocampus in nine patients (mean age 11.8 years) and nine age-matched healthy controls. The study was designed with four visits: baseline, 6-month, 15-month, and 27-month follow-ups.

Results

Patients had 24 % higher overall mean ADC in the hippocampus compared with controls (p?=?0.003). Post hoc analyses revealed significantly elevated ADC at baseline (p?=?0.003) and at the 27-month follow-up (p?=?0.006). Nevertheless, patients performed normally on a verbal memory test considered to be a hippocampus-related function. Relative to controls, patients' performance on the tests of the visual–spatial working memory decreased over time (group by visit, p?=?0.036). Both patients and controls showed a decline in motor speed with increasing ADC in the globus pallidus and putamen.

Conclusions

Childhood brain malignancies and their treatment may affect gray matter microstructure as measured by water diffusion. Significant findings in the hippocampus but not other regions suggest that differences in tissue sensitivity to disease- and treatment-related injury among gray matter regions may exist. ADC in basal ganglia may be associated with motor performance.     

Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects

Frodl T, Skokauskas N. Meta‐analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Objective: About 50–80% of ADHD cases have been found to persist into adulthood, but ADHD symptoms change with age. The aim of this study was to perform a meta‐analysis of MRI voxel‐based morphometry (VBM) and manual tracing studies to identify the differences between adults and children with ADHD as well as between treated and untreated individuals. Method: Several databases were searched using keywords ‘attention‐deficit and MRI’, ‘ADHD and MRI’. Gray matter volumes from VBM studies and caudate volumes from tracing studies of patients and controls were analyzed using signed differential mapping. Results: Meta‐analyses detected reduced right globus pallidus and putamen volumes in VBM studies as well as decreased caudate volumes in manual tracing studies in children with ADHD. Adult patients with ADHD showed volume reduction in the anterior cingulate cortex (ACC). A higher percentage of treated participants were associated with less changes. Conclusion: Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non‐treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.     

Resting‐state functional connectivity of the human hippocampus in periadolescent children: Associations with age and memory performance

The hippocampus is necessary for declarative (relational) memory, and the ability to form hippocampal‐dependent memories develops through late adolescence. This developmental trajectory of hippocampal‐dependent memory could reflect maturation of intrinsic functional brain networks, but resting‐state functional connectivity (rs‐FC) of the human hippocampus is not well‐characterized for periadolescent children. Measuring hippocampal rs‐FC in periadolescence would thus fill a gap, and testing covariance of hippocampal rs‐FC with age and memory could inform theories of cognitive development. Here, we studied hippocampal rs‐FC in a cross‐sectional sample of healthy children (N = 96; 59 F; age 9–15 years) using a seed‐based approach, and linked these data with NIH Toolbox measures, the Picture‐Sequence Memory Test (PSMT) and the List Sorting Working Memory Test (LSWMT). The PSMT was expected to rely more on hippocampal‐dependent memory than the LSWMT. We observed hippocampal rs‐FC with an extensive brain network including temporal, parietal, and frontal regions. This pattern was consistent with prior work measuring hippocampal rs‐FC in younger and older samples. We also observed novel, regionally specific variation in hippocampal rs‐FC with age and hippocampal‐dependent memory but not working memory. Evidence consistent with these findings was observed in a second, validation dataset of similar‐age healthy children drawn from the Philadelphia Neurodevelopment Cohort. Further, a cross‐dataset analysis suggested generalizable properties of hippocampal rs‐FC and covariance with age and memory. Our findings connect prior work by describing hippocampal rs‐FC and covariance with age and memory in typically developing periadolescent children, and our observations suggest a developmental trajectory for brain networks that support hippocampal‐dependent memory.     

Structural correlates underlying accelerated magnetic stimulation in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique with great potential in the treatment of Parkinson''s disease (PD). This study aimed to investigate the clinical efficacy of accelerated rTMS and to understand the underlying neural mechanism. In a double‐blinded way, a total of 42 patients with PD were randomized to receive real (n = 22) or sham (n = 20) continuous theta‐burst stimulation (cTBS) on the left supplementary motor area (SMA) for 14 consecutive days. Patients treated with real cTBS, but not with sham cTBS, showed a significant improvement in Part III of the Unified PD Rating Scale (p < .0001). This improvement was observed as early as 1 week after the start of cTBS treatment, and maintained 8 weeks after the end of the treatment. These findings indicated that the treatment response was swift with a long‐lasting effect. Imaging analyses showed that volume of the left globus pallidus (GP) increased after cTBS treatment. Furthermore, the volume change of GP was mildly correlated with symptom improvement and associated with the baseline fractional anisotropy of SMA‐GP tracts. Together, these findings implicated that the accelerated cTBS could effectively alleviate motor symptoms of PD, maybe by modulating the motor circuitry involving the SMA‐GP pathway.     

Longitudinal neural connection detection using a ferritin‐encoding adeno‐associated virus vector and in vivo MRI method

The investigation of neural circuits is important for interpreting both healthy brain function and psychiatric disorders. Currently, the architecture of neural circuits is always investigated with fluorescent protein encoding neurotropic virus and ex vivo fluorescent imaging technology. However, it is difficult to obtain a whole‐brain neural circuit connection in living animals, due to the limited fluorescent imaging depth. Herein, the noninvasive, whole‐brain imaging technique of MRI and the hypotoxicity virus vector AAV (adeno‐associated virus) were combined to investigate the whole‐brain neural circuits in vivo. AAV2‐retro are an artificially‐evolved virus vector that permits access to the terminal of neurons and retrograde transport to their cell bodies. By expressing the ferritin protein which could accumulate iron ions and influence the MRI contrast, the neurotropic virus can cause MRI signal changes in the infected regions. For mice injected with the ferritin‐encoding virus vector (rAAV2‐retro‐CAG‐Ferritin) in the caudate putamen (CPu), several regions showed significant changes in MRI contrasts, such as PFC (prefrontal cortex), HIP (hippocampus), Ins (insular cortex) and BLA (basolateral amygdala). The expression of ferritin in those regions was also verified with ex vivo fluorescence imaging. In addition, we demonstrated that changes in T2 relaxation time could be used to identify the spread area of the virus in the brain over time. Thus, the neural connections could be longitudinally detected with the in vivo MRI method. This novel technique could be utilized to observe the viral infection process and detect the neural circuits in a living animal.     

Specific age‐correlated activation of top hierarchical motor control areas during gait‐like plantar stimulation: An fMRI study

A better understanding of gait disorders that are associated with aging is crucial to prevent adverse outcomes. The functional study of gait remains a thorny issue due to technical constraints inherent to neuroimaging procedures, as most of them require to stay supine and motionless. Using an MRI‐compatible system of boots reproducing gait‐like plantar stimulation, we investigated the correlation between age and brain fMRI activation during simulated gait in healthy adults. Sixty‐seven right‐handed healthy volunteers aged between 20 and 77 years old (49.2 ± 18.0 years; 35 women) were recruited. Two paradigms were assessed consecutively: (a) gait‐like plantar stimulation and (b) chaotic and not gait‐related plantar stimulation. Resulting statistical parametric maps were analyzed with a multiple‐factor regression that included age and a threshold determined by Monte‐Carlo simulation to fulfill a family‐wise error rate correction of p < .05. In the first paradigm, there was an age‐correlated activation of the right pallidum, thalamus and putamen. The second paradigm showed an age‐correlated deactivation of both primary visual areas (V1). The subtraction between results of the first and second paradigms showed age‐correlated activation of the right presupplementary motor area (Brodmann Area [BA] 6) and right mid‐dorsolateral prefrontal cortex (BA9‐10). Our results show age‐correlated activity in areas that have been associated with the control of gait, highlighting the relevance of this simulation model for functional gait study. The specific progressive activation of top hierarchical control areas in simulated gait and advancing age corroborate a progressive loss of automation in healthy older adults.     

Alterations in regional brain concentrations of neurotensin and bombesin in Parkinson's disease

Frozen samples of postmortem human brain tissue from patients with Parkinson's disease (n = 25) and control patients who died without neurological disease (n = 25) were assayed for neurotensin and bombesin by specific radioimmunoassay. Twelve brain regions were examined: substantia nigra, ventral tegmental area, periaqueductal gray matter, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, nucleus accumbens, frontal cortex, cingulate cortex, and entorhinal cortex. In patients with Parkinson's disease, the concentration of bombesin was significantly decreased in the caudate nucleus and globus pallidus, and the concentration of neurotensin was significantly reduced in the hippocampus. The concentration of neither peptide was significantly altered in the substantia nigra or ventral tegmental area, two regions known to exhibit reductions in other neurotransmitter substances.     

Altered brain iron content and deposition rate in Huntington’s disease as indicated by quantitative susceptibility MRI

Altered brain iron content in the striatum of premanifest and manifest Huntington’s disease (HD) has been reported. However, its natural history remains unclear. This study aims to investigate altered brain iron content in premanifest and early HD, and the iron deposition rate in these patients through a longitudinal one-year follow-up test, with quantitative magnetic susceptibility as an iron imaging marker. Twenty-four gene mutation carriers divided into three groups (further-from-onset, closer-to-onset and early HD) and 16 age-matched healthy controls were recruited at baseline, and of these, 14 carriers and 7 controls completed the one-year follow-up. Quantitative magnetic susceptibility and effective transverse relaxation rate () were measured at 7.0 Tesla and correlated with atrophy and available clinical and cognitive measurements. Higher susceptibility values indicating higher iron content in the striatum and globus pallidus were only observed in closer-to-onset (N = 6, p < 0.05 in caudate and p < 0.01 in putamen) and early HD (N = 9, p < 0.05 in caudate and globus pallidus and p < 0.01 in putamen). Similar results were found by measurement. Such increases directly correlated with HD CAG–age product score and brain atrophy, but not with motor or cognitive scores. More importantly, a significantly higher iron deposition rate (11.9%/years in caudate and 6.1%/years in globus pallidus) was firstly observed in closer-to-onset premanifest HD and early HD as compared to the controls. These results suggest that monitoring brain iron may provide further insights into the pathophysiology of HD disease progression, and may provide a biomarker for clinical trials.     

Effective connectivity in the default mode network is distinctively disrupted in Alzheimer's disease—A simultaneous resting‐state FDG‐PET/fMRI study

A prominent finding of postmortem and molecular imaging studies on Alzheimer''s disease (AD) is the accumulation of neuropathological proteins in brain regions of the default mode network (DMN). Molecular models suggest that the progression of disease proteins depends on the directionality of signaling pathways. At network level, effective connectivity (EC) reflects directionality of signaling pathways. We hypothesized a specific pattern of EC in the DMN of patients with AD, related to cognitive impairment. Metabolic connectivity mapping is a novel measure of EC identifying regions of signaling input based on neuroenergetics. We simultaneously acquired resting‐state functional MRI and FDG‐PET data from patients with early AD (n = 35) and healthy subjects (n = 18) on an integrated PET/MR scanner. We identified two distinct subnetworks of EC in the DMN of healthy subjects: an anterior part with bidirectional EC between hippocampus and medial prefrontal cortex and a posterior part with predominant input into medial parietal cortex. Patients had reduced input into the medial parietal system and absent input from hippocampus into medial prefrontal cortex (p < 0.05, corrected). In a multiple linear regression with unimodal imaging and EC measures (F _4,25 = 5.63, p = 0.002, r ² = 0.47), we found that EC (β = 0.45, p = 0.012) was stronger associated with cognitive deficits in patients than any of the PET and fMRI measures alone. Our approach indicates specific disruptions of EC in the DMN of patients with AD and might be suitable to test molecular theories about downstream and upstream spreading of neuropathology in AD.     

Striatal volumes in pediatric bipolar patients with and without comorbid ADHD

The most prevalent comorbid disorder in pediatric bipolar disorder (BD) is attention-deficit/hyperactivity disorder (ADHD). As caudate volume abnormalities have been demonstrated in both BD and ADHD, this study sought to determine whether these findings could be attributed to separable effects from either diagnosis. High resolution anatomical magnetic resonance (MRI) images were obtained from youth in 4 groups: BD with comorbid ADHD (n=17), BD without comorbid ADHD (n=12), youth with ADHD alone (n=11), and healthy control subjects (n=24). Caudate, putamen, and globus pallidus volumes were manually traced for each subject using BrainImageJava software by a reliable rater blinded to diagnosis. There was a significant effect of diagnosis on striatal volumes, with ADHD associated with decreased caudate and putamen volumes, and BD associated with increased caudate, putamen, and globus pallidus volumes. Thus, the presence or absence of comorbid ADHD in patients with BD was associated with distinct alterations in caudate volumes, suggesting that these groups have different, but related, mechanisms of neuropathology.     

The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women

Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi‐modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two‐time points of their MC. CBF was derived from pseudo‐continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = −.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MC‐related hormone fluctuations in the design of functional MRI studies in this population.     

Brain microstructural properties related to subjective well-being: diffusion tensor imaging analysis

Although it is known that health is not merely the absence of disease, the positive aspects of mental health have been less comprehensively researched compared with its negative aspects. Subjective well-being (SWB) is one of the indicators of positive psychology, and high SWB is considered to benefit individuals in multiple ways. However, the neural mechanisms underlying individual differences in SWB remain unclear, particularly in terms of brain microstructural properties as detected by diffusion tensor imaging. The present study aimed to investigate the relationship between measurements of diffusion tensor imaging [mean diffusivity (MD) and fractional anisotropy] and the degree of SWB as measured using a questionnaire. Voxel-based analysis was used to investigate the association between MD and SWB scores in healthy young adults (age, 20.7 ± 1.8 years; 695 males and 514 females). Higher levels of SWB were found to be associated with lower MD in areas surrounding the right putamen, insula, globus pallidus, thalamus and caudate. These results indicated that individual SWB is associated with variability in brain microstructural properties.