Imaging cortical activity following affective stimulation with a high temporal and spatial resolution

Background  

The affective and motivational relevance of a stimulus has a distinct impact on cortical processing, particularly in sensory areas. However, the spatial and temporal dynamics of this affective modulation of brain activities remains unclear. The purpose of the present study was the development of a paradigm to investigate the affective modulation of cortical networks with a high temporal and spatial resolution. We assessed cortical activity with MEG using a visual steady-state paradigm with affective pictures. A combination of a complex demodulation procedure with a minimum norm estimation was applied to assess the temporal variation of the topography of cortical activity.     

Laryngeal and respiratory activity during vocalization in macaque monkeys

The present study describes the laryngeal and respiratory muscle activity associated with vocalizations in macaque monkeys. During the bark vocalization, a short, aperiodic call, the cricothyroid, thyroarytenoid, rectus abdominis, and intercostals were active while the posterior cricoarytenoid and diaphragm were quiet. During the coo vocalization, a longer, clear call, the cricothyroid, thyroarytenoid, intercostals, rectus abdominis, and diaphragm were active. In one monkey, the posterior cricoarytenoid was also active during the call, while in another monkey it was not. Laryngeal muscle activity was correlated with the amplitude and duration of the coo call. Results suggest that the amplitude and duration differences between calls are determined primarily by laryngeal modification of the airflow, and that the differences in posterior cricoarytenoid activity may be due to differences in voice intensity.     

Imaging iron stores in the brain using magnetic resonance imaging

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.     

Time-invariant person-specific frequency templates in human brain activity

The various human brain tasks are performed at different locations and time scales. Yet, we discovered the existence of time-invariant (above an essential time scale) partitioning of the brain activity into personal state-specific frequency bands. For that, we perform temporal and ensemble averaging of best wavelet packet bases from multielectrode electroencephalogram recordings. These personal frequency bands provide new templates for quantitative analyses of brain function, e.g., normal versus epileptic activity.     

Development of visually evoked cortical activity in infant macaque monkeys studied longitudinally with fMRI

We studied the development of visual activation longitudinally in two infant monkeys aged 103-561 days using the BOLD fMRI technique under opiate anesthesia and compared the results with those obtained in three adult animals studied under identical conditions. Visual activation in primary visual cortex, V1, was strong and reliable in monkeys of the youngest and oldest ages, showing that functional imaging techniques give qualitatively similar results in infants and adults. Visual activation in extrastriate areas involved in processing motion (MT/V5) and form (V4) was not evident in the younger animals, but became more adult-like in the older animals. This delayed onset of measurable BOLD responses in extrastriate visual cortex may reflect delayed development of visual responses in these areas, although at this stage it is not possible to rule out either effects of anesthesia or of changes in cerebral vascular response mechanisms as the cause. The demonstration of visually evoked BOLD responses in young monkeys shows that the BOLD fMRI technique can usefully be employed to address functional questions of brain development.     

BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury

Background  

Mechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury.     

Increased glucose concentration in the hippocampus in early Alzheimer's disease following oral glucose ingestion

Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD) - a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre- and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P < .01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1H MR spectroscopy.     

Community structure and modularity in networks of correlated brain activity

Functional connectivity patterns derived from neuroimaging data may be represented as graphs or networks, with individual image voxels or anatomically-defined structures representing the nodes, and a measure of correlation between the responses in each pair of nodes determining the edges. This explicit network representation allows network-analysis approaches to be applied to the characterization of functional connections within the brain. Much recent research in complex networks has focused on methods to identify community structure, i.e. cohesive clusters of strongly interconnected nodes. One class of such algorithms determines a partition of a network into 'sub-networks' based on the optimization of a modularity parameter, thus also providing a measure of the degree of segregation versus integration in the full network. Here, we demonstrate that a community structure algorithm based on the maximization of modularity, applied to a functional connectivity network calculated from the responses to acute fluoxetine challenge in the rat, can identify communities whose distributions correspond to anatomically meaningful structures and include compelling functional subdivisions in the brain. We also discuss the biological interpretation of the modularity parameter in terms of segregation and integration of brain function.     

In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal column transection injury

Longitudinal Myelin Water Imaging was carried out in vivo to characterize white matter damage following dorsal column transection (DC Tx) injury at the lumbar level L1 of rat spinal cords. A transmit–receive implantable coil system was used to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal cords of 16 rats at one week pre-injury as well as 3 and 8 weeks post-injury (117 microns in-plane resolution and 1.5 mm slice thickness). In addition, ex vivo MSE and DTI data were acquired from cords fixed and excised at 3 or 8 weeks post injury using a solenoid coil. The MSE data were used to generate Myelin Water Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were acquired to study damage to the axons. Myelin damage was assessed histologically with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen-MBP) staining, and axonal damage was assessed by neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and histological measures of injury were studied in the dorsal column at 5 mm cranial and 5 mm caudal to injury epicenter. MWF increased significantly at 3 weeks post-injury at both the cranial and caudal sites, relative to baseline. The values on the cranial side of injury returned to baseline at 8 weeks post-injury but remained elevated on the caudal side. This trend was found in both in vivo and ex vivo data. This MWF increase was likely due to the presence of myelin debris, which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC and dgen-MBP stains displayed similar trends. MWF showed significant correlation with EC staining (R = 0.63, p = 0.005 in vivo and R = 0.74, p = 0.0001 ex vivo). MWF also correlated strongly with the dgen-MBP stain, but only on the cranial side (R = 0.64, p = 0.05 in vivo; R = 0.63, p = 0.038 ex vivo). This study demonstrates that longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx model of injury in the rat spinal cord.     

Background and evoked activity and their interaction in the human brain

Most functional neuroimaging studies have investigated brain activity evoked by certain types of stimulation or tasks. In recent years, resting brain activity and its influence on evoked activity has become accessible for investigation. However, despite numerous studies on background and evoked activities, either observed with vascular (functional magnetic resonance imaging, positron emission tomography, optical) or electrophysiological (electroencephalography, magnetoencephalography) or a combination of both methods, so far, there is no generally accepted view concerning both the precise meaning of background activity and its relationship to evoked activity. In this article, we give an overview of the current knowledge on this issue and we review recent studies examining the influence of ongoing activity on behavioral responses and the relationship between ongoing and evoked activity.     

Impaired functionality of reperfused brain tissue following short transient focal ischemia in rats

Functional magnetic resonance imaging (fMRI) has been applied to study the consequences of transient focal ischemia on neuronal excitability in the rat brain. The experimental paradigm consisted of measuring the changes in local cerebral blood volume (CBV) induced by systemic infusion of the GABA(A) antagonist bicuculline after occlusion of the middle cerebral artery (MCA) for durations of 5, 15, 30 and 60 min using the intraluminal thread model. fMRI studies were carried out 60 min after successful reperfusion of the ischemic territory. Bicuculline-induced dynamic changes in local CBV were assessed in three brain regions: Parietal cortex, caudate putamen and thalamus. The measured CBV response was negatively correlated with the ischemia duration. Additionally, the three regions showed different vulnerability to the transient MCA occlusion, caudate being the most susceptible followed by parietal cortex and thalamus. The fMRI signals weakly correlated with basal CBF and CBV following reperfusion. Our results indicate that fMRI is a sensitive method to assess functional integrity of the brain. Activation maps allow to quantitatively assess the functionally compromized territory at an early stage following the ischemic event prior to the manifestation of pathomorphological changes.     

Regional brain activity after prolonged cholinergic enhancement in early Alzheimer's disease

This functional magnetic resonance imaging (fMRI) study examined changes in brain activation after prolonged (20 weeks) and stabilized treatment with the cholinesterase inhibitor galantamine in a small group of patients with very mild Alzheimer's disease (AD). Two cognitive activation paradigms were chosen: one requiring semantic association and the other relying on attention and requiring target detection. A group of age- and education-matched healthy controls was also scanned for comparison. A modest (but not statistically significant) improvement in behavioral scores after treatment was observed in both fMRI tasks. There were brain activation increases in the semantic association task after treatment, and the differences in brain activation present in the comparison of AD patients' baseline images with those of controls were not detectable after treatment. In the target detection task, regions that were activated in the elderly controls but not in the baseline images of the AD group also showed significant activation after treatment. Overall, however, the increases were modest and might reflect the heterogeneity of clinical response to treatment in this small group. Future pharmacological fMRI studies should include clinical response as a factor in the analysis of cholinergic enhancement effects in AD patients.     

Enzymatic studies in foetal brain and liver of mouse following in utero exposure to ultrasound

Lactate, malate and succinate dehydrogenases (LDH, MDH and SDH) were estimated in the foetal brain and liver following in utero exposure of mice to a continuous wave of unfocussed ultrasound. Enzymes in both tissues showed a significant increase (P greater than 0.001), indicating high energy demand due to depletion of oxygen. The increase was recorded even on the twentieth day of pregnancy.     

Brain activity in aphonia after a coughing episode: different brain activity in healthy whispering and pathological aphonic conditions

A 48-year-old woman visited the authors' clinic because of aphonia. Laryngeal fiberscopic examination indicated laryngitis and bronchitis, and the authors recognized glottal incompetence when she tried to phonate. The authors performed a functional magnetic resonance imaging (f-MRI) study on the patient's first visit to their clinic and a second study 35 days after the first visit (30 days after the bronchitis and coughing had completely resolved). The brain activity shown on f-MRI differed markedly in the ordinary speaking and whispering phonation modes at the second visit. This suggests that whispering and pathological aphonia result from completely different brain activity, at least in this specific patient.     

Reduction of the hand representation in the ipsilateral primary motor cortex following unilateral section of the corticospinal tract at cervical level in monkeys

Background  

After sub-total hemi-section of cervical cord at level C7/C8 in monkeys, the ipsilesional hand exhibited a paralysis for a couple of weeks, followed by incomplete recovery of manual dexterity, reaching a plateau after 40–50 days. Recently, we demonstrated that the level of the plateau was related to the size of the lesion and that progressive plastic changes of the motor map in the contralesional motor cortex, particularly the hand representation, took place following a comparable time course. The goal of the present study was to assess, in three macaque monkeys, whether the hand representation in the ipsilesional primary motor cortex (M1) was also affected by the cervical hemi-section.     

Initial attempts at directly detecting alpha wave activity in the brain using MRI

The “direct detection” of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus.

Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified.     

Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis

Objective

The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T_1ρ and T₂ mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention.

Methods

Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis.

Results

Consistent with previous studies, initial elevations in T_1ρ and T₂ values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12-week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T_1ρ and T₂ values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA.

Conclusion

We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late-stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo.