Magnetic resonance imaging (MRI) captures the dynamics of brain development with multiple modalities that quantify both structure and function. These measurements may yield valuable insights into the neural patterns that mark healthy maturation or that identify early risk for psychiatric disorder. The Pediatric Template of Brain Perfusion (PTBP) is a free and public neuroimaging resource that will help accelerate the understanding of childhood brain development as seen through the lens of multiple modality neuroimaging and in relation to cognitive and environmental factors. The PTBP uses cross-sectional and longitudinal MRI to quantify cortex, white matter, resting state functional connectivity and brain perfusion, as measured by Arterial Spin Labeling (ASL), in 120 children 7–18 years of age. We describe the PTBP and show, as a demonstration of validity, that global summary measurements capture the trajectories that demarcate critical turning points in brain maturation. This novel resource will allow a more detailed understanding of the network-level, structural and functional landmarks that are obtained during normal adolescent brain development.

To determine how arterial spin labeling (ASL) measured perfusion relates to baseline metabolism, we compared resting state cerebral perfusion using pseudo-continuous ASL and cerebral glucose metabolism using (18)F-FDG PET in 20 normal volunteers. Greater regional metabolism relative to perfusion was observed in the putamen, orbitofrontal and temporal lobes, whereas perfusion was relatively higher in the hippocampus and insula. In a region of interest analysis limited to gray matter, the overall mean correlation between perfusion and metabolism across voxels was r=0.43 with considerable regional variability. Cross-voxel correlations between relative perfusion and metabolism in mean ASL and PET images of all 20 subjects were the highest in the striatum (caudate: r=0.78; putamen: r=0.81), and the lowest in medial temporal structures (amygdala: r=0.087; hippocampus: r=-0.26). Correlations between mean relative perfusion and metabolism across 20 subjects were the highest in the striatum (caudate: r=0.76; putamen: r=0.58), temporal lobe (r=0.59), and frontal lobe (r=0.52), but very poor in all other structures (r<0.3), particularly in caudal structures such as the hippocampus (r=-0.0026), amygdala (r=0.18), and insula (r=0.14). Although there was good overall correlation between perfusion and glucose metabolism, regional variability should be considered when using either ASL or (18)F-FDG PET as surrogate markers for neural activity.

Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic fields induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic fields. Following validation on a phantom with a known path of electric current and induced magnetic field, the proposed MRI technique was applied to a human limb (to demonstrate in-vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic fields as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic fields linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.

Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (ΔCBV) and change in arterial pressure (ΔBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia.

Recent clinical trials of transcranial direct current stimulation (tDCS) in depression have shown contrasting results. Consequently, we used in-vivo neuroimaging to confirm targeting and modulation of depression-relevant neural circuitry by tDCS. Depressed participants (N = 66, Baseline Hamilton Depression Rating Scale (HDRS) 17-item scores ≥14 and <24) were randomized into Active/Sham and High-definition (HD)/Conventional (Conv) tDCS groups using a double-blind, parallel design, and received tDCS individually targeted at the left dorsolateral prefrontal cortex (DLPFC). In accordance with Ampere’s Law, tDCS currents were hypothesized to induce magnetic fields at the stimulation-target, measured in real-time using dual-echo echo-planar-imaging (DE-EPI) MRI. Additionally, the tDCS treatment trial (consisting of 12 daily 20-min sessions) was hypothesized to induce cerebral blood flow (CBF) changes post-treatment at the DLPFC target and in the reciprocally connected anterior cingulate cortex (ACC), measured using pseudo-continuous arterial spin labeling (pCASL) MRI. Significant tDCS current-induced magnetic fields were observed at the left DLPFC target for both active stimulation montages (Brodmann’s area (BA) 46: pHD = 0.048, Cohen’s dHD = 0.73; pConv = 0.018, dConv = 0.86; BA 9: pHD = 0.011, dHD = 0.92; pConv = 0.022, dConv = 0.83). Significant longitudinal CBF increases were observed (a) at the left DLPFC stimulation-target for both active montages (pHD = 3.5E−3, dHD = 0.98; pConv = 2.8E−3, dConv = 1.08), and (b) at ACC for the HD-montage only (pHD = 2.4E−3, dHD = 1.06; pConv = 0.075, dConv = 0.64). These results confirm that tDCS-treatment (a) engages the stimulation-target, and (b) modulates depression-relevant neural circuitry in depressed participants, with stronger network-modulations induced by the HD-montage. Although not primary outcomes, active HD-tDCS showed significant improvements of anhedonia relative to sham, though HDRS scores did not differ significantly between montages post-treatment.

A B S T R A C TTranscranial direct current stimulation (tDCS) is a low intensity neuromodulation technique shown to elicit therapeutic effects in a number of neuropsychological conditions. Independent randomized sham-controlled trials and meta-and mega-analyses demonstrate that tDCS targeted to the left dorsolateral prefrontal cortex can produce a clinically meaningful response in patients with major depressive disorder (MDD), but effects are small to moderate in size. However, the heterogeneous presentation, and the neurobiology underlying particular features of depression suggest clinical outcomes might benefit from empirically informed patient selection. In this review, we summarize the status of tDCS research in MDD with focus on the clinical, biological, and intrinsic and extrinsic factors shown to enhance or predict antidepressant response. We also discuss research strategies for optimizing tDCS to improve patient-specific clinical outcomes. TDCS appears suited for both bipolar and unipolar depression, but is less effective in treatment resistant depression. TDCS may also better target core aspects of depressed mood over vegetative symptoms, while pretreatment patient characteristics might inform subsequent response. Peripheral blood markers of gene and immune system function have not yet proven useful as predictors or correlates of tDCS response. Though further research is needed, several lines of evidence suggest that tDCS administered in combination with pharmacological and cognitive behavioral interventions can improve outcomes. Tailoring stimulation to the functional and structural anatomy and/or connectivity of individual patients can maximize physiological response in targeted networks, which in turn could translate to therapeutic benefits. ⁎ Corresponding author at: 635 Charles E Young Drive South Ste 225,

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Despite being a popular neuromodulation technique, clinical translation of transcranial direct current stimulation (tDCS) is hampered by variable responses observed within treatment cohorts. Addressing this challenge has been difficult due to the lack of an effective means of mapping the neuromodulatory electromagnetic fields together with the brain's response. In this study, we present a novel imaging technique that provides the capability of concurrently mapping markers of tDCS currents, as well as the brain's response to tDCS. A dual-echo echo-planar imaging (DE-EPI) sequence is used, wherein the phase of the acquired MRI-signal encodes the tDCS current induced magnetic field, while the magnitude encodes the blood oxygenation level dependent (BOLD) contrast. The proposed technique was first validated in a custom designed phantom. Subsequent test-retest experiments in human participants showed that tDCS-induced magnetic fields can be detected reliably in vivo. The concurrently acquired BOLD data revealed large-scale networks characteristic of a brain in restingstate as well as a 'cathodal' and an 'anodal' resting-state component under each electrode. Moreover, 'cathodal's BOLD-signal was observed to significantly decrease with the applied current at the group level in all datasets. With its ability to image markers of electromagnetic cause as well as neurophysiological changes, the proposed technique may provide an effective means to visualize neural engagement in tDCS at the group level. Our technique also contributes to addressing confounding factors in applying BOLD fMRI concurrently with tDCS.