Blaise B. Frederick

Activation of suprachiasmatic nuclei and primary visual cortex depends upon time of day

The human suprachiasmatic nucleus (SCN), the master biological clock, is a small (∼2 mm3) and deep structure located in the anterior hypothalamus. Previous methods do not allow in vivo study of the human SCN in a non‐invasive manner. Therefore, we explored blood oxygen level‐dependent (BOLD)‐functional magnetic resonance imaging (fMRI) with OFF–ON–OFF block‐designed visual stimuli to record the activities in the ‘SCN and peri SCN in the anterior hypothalamus’ (SCN+) and the primary visual area V1 using a 3T Siemens scanner and six normal subjects. We found that: (i) the BOLD‐fMRI response to light and the mean of percentage activation in the SCN+ at midday was significantly less than that at night; and (ii) the number of activated voxels in most of the visual area V1 at midday was significantly higher than that at night. We conclude that BOLD‐fMRI responses to light in the SCN+ and the V1 areas vary with time of day. This conclusion is consistent with: (i) the previously measured phase–response curve to light [J. Physiol., 549.3 (2003) 945] for the SCN activity at critical intensity threshold; and (ii) the interaction of the melanopsin‐based signals with the rod‐cone signals at the ‘giant’ retinal ganglion cells [Nature, 433 (2005) 749] for the V1 activity.

Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI-based delayed matching to sample task.

Nicotine dependence is a chronic and difficult to treat disorder. While environmental stimuli associated with smoking precipitate craving and relapse, it is unknown whether smoking cues are cognitively processed differently than neutral stimuli. To evaluate working memory differences between smoking‐related and neutral stimuli, we conducted a delay‐match‐to‐sample (DMS) task concurrently with functional magnetic resonance imaging (fMRI) in nicotine‐dependent participants. The DMS task evaluates brain activation during the encoding, maintenance and retrieval phases of working memory. Smoking images induced significantly more subjective craving, and greater midline cortical activation during encoding in comparison to neutral stimuli that were similar in content yet lacked a smoking component. The insula, which is involved in maintaining nicotine dependence, was active during the successful retrieval of previously viewed smoking versus neutral images. In contrast, neutral images required more prefrontal cortex‐mediated active maintenance during the maintenance period. These findings indicate that distinct brain regions are involved in the different phases of working memory for smoking‐related versus neutral images. Importantly, the results implicate the insula in the retrieval of smoking‐related stimuli, which is relevant given the insulas emerging role in addiction.

Brain Changes to Hypocapnia Using Rapidly Interleaved Phosphorus-Proton Magnetic Resonance Spectroscopy at 4 T

Substantial controversy persists in the literature concerning the physiologic consequences hypocapnia, or low partial pressure of carbon dioxide (PaCO2). Invasive animal studies have demonstrated large pH increases (>0.25 U), phosphocreatine (PCr) decreases (>30%), and adenosine triphosphate (ATP) decreases (>10%) after hyperventilation (HV) (20 mm Hg PaCO2). However, using magnetic resonance spectroscopy, HV studies in awake humans have demonstrated only small pH changes (∼0.05 U) and no changes in PCr or ATP. It remains important to ascertain whether this failure to detect PCr changes in human studies reflects a true absence of changes, or a limitation in data fidelity. The present study used a rapidly interleaved phosphorus-proton spectroscopy acquisition from large samples at high magnetic field (4 T), to measure pH, PCr, inorganic phosphate, β-ATP, and lactate changes with high temporal and signal sensitivity. Five of six subjects had usable data. During 20 mins HV, PaCO2 reached a minimum at 16 mins (17 mm Hg); however, the maximum pH change (+0.047) peaked earlier (14 mins). Maximal lactate increases were measured at 15 mins. By 10 mins, maximum changes were observed for PCr (−3.4%) and inorganic phosphate (+6.4%). No changes in β-ATP were observed. The peak in pH, despite continued decreases in PaCO2, suggests active buffering during HV. These data, and the small magnitude of early PCr and inorganic phosphate changes, do not support substantial energy compromise during HV. Other mitigating factors, such as anesthesia-induced deregulation of the cerebrovasculature, might have contributed to the exaggerated metabolic changes observed in previous animal investigations.

Calculations of BOLD signals by use of NIRS photon migration hitting density functions

We present a comparison of NIRS data and BOLD signals concurrently acquired during motor area activation. The BOLD signals are calculated by applying a weighted average according to the photon migration hitting density function.

Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic imaging and resonance study

Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p = 0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p = 0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r = +0.661, p = 0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r = +0.522, p = 0.000; left amygdala: r = +0.651, p = 0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p = 0.03) and positively correlated with intra DMPFC connectivity (r = +0.548, p = 0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.

Salience network coupling is linked to both tobacco smoking and symptoms of attention deficit hyperactivity disorder (ADHD)

INTRODUCTION Attention deficit hyperactivity disorder (ADHD) symptoms, even those below diagnostic threshold, enhance the likelihood of nicotine dependence, suggesting a neurobiological link between disorders. Of particular interest is the salience network (SN), which mediates attention to salient internal/external stimuli to guide behavior and is anchored by the dorsal anterior cingulate cortex (dACC) and bilateral anterior insula (AI). Disrupted interactions between the SN and the default mode (DMN) and central executive networks (CEN) have been noted in both ADHD and nicotine dependence. Further, enhanced intra-SN coupling between the dACC-AI influences aspects of nicotine dependence such as reactivity to smoking cues. METHODS To identify links between SN functional connectivity and ADHD symptoms in nicotine dependence, we compared 21 nicotine dependent individuals with 17 non-smokers on ADHD symptoms as measured by the ADHD self-report scale (ASRS) and resting state intra and inter-SN functional connectivity. RESULTS Relative to healthy controls, nicotine dependent individuals had significantly higher ASRS scores and greater dACC-AI coupling. No group differences were noted on inter-SN network coupling. A significant association was found between ASRS and dACC-AI coupling both in the entire cohort and specifically when evaluating nicotine dependent individuals alone. CONCLUSIONS The greater ASRS scores in nicotine dependent individuals is in line with existent literature and the stronger dACC-AI coupling in smokers further supports the role of this network in nicotine dependence. The significant association between dACC-AI coupling and ASRS suggests that intra-SN coupling strength may impact neurocognitive functioning associated with both ADHD symptoms and nicotine dependence.